Publications by authors named "Sean P Cleary"

103 Publications

Multifocality is not associated with worse survival in sporadic pancreatic neuroendocrine tumors.

J Surg Oncol 2021 Jul 26. Epub 2021 Jul 26.

Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Background And Objectives: Pancreatic neuroendocrine tumors (pNETs) in patients with hereditary cancer syndromes are typically multifocal. In contrast, sporadic pNETs are usually unifocal and the incidence of multifocal sporadic pNETs is unknown. The primary aim of this study was to investigate the incidence of multifocality in sporadic pNETs and any associated effect on recurrence risk and survival.

Methods: Patients who underwent resection of pNETs at Mayo Clinic from 2000 to 2019 were identified and clinical data were obtained from medical records. Syndromic disease was defined as pNETs arising in the setting of a hereditary cancer syndrome. Statistical comparisons were made using χ , Fisher's exact, and Kruskal-Wallis tests and survival was assessed using the Kaplan-Meier method.

Results: Six hundred and sixty-one patients with sporadic pNETs and fifty-nine with syndromic pNETs were identified. Multifocal disease was present in 4.8% of sporadic patients and 84.7% of syndromic patients (p < .001). Within patients with sporadic pNETs, clinicopathologic features and recurrence-free and overall survival were similar between patients with unifocal and multifocal disease.

Conclusions: Multifocal sporadic pNETs are rare and multifocality is not associated with worse survival or increased recurrence risk. Patients with multifocal sporadic pNETs can likely be safely managed with a combination of resection and observation as indicated for each tumor.
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http://dx.doi.org/10.1002/jso.26618DOI Listing
July 2021

Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer.

Cancer Med 2021 Jul 21. Epub 2021 Jul 21.

Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic Rochester, Rochester, Minnesota, USA.

Introduction: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy.

Methods: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention-to-treat (ITT) basis.

Results: Twelve thousand and eighty-nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT-neoadjuvant cohort (27.9 vs. 22 months) to UFS.

Conclusion: Despite the perceived benefit of UFS, only 1-in-5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT-neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of 'optimal' survival benefit with UFS in anatomically resectable PDAC.
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http://dx.doi.org/10.1002/cam4.4144DOI Listing
July 2021

Intraoperative bile duct cultures in patients undergoing pancreatic head resection: Prospective comparison of bile duct swab versus bile duct aspiration.

Surgery 2021 Jul 2. Epub 2021 Jul 2.

Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN. Electronic address:

Background: Postoperative surgical site infection is a major source of morbidity after pancreatic head resections, and data suggest bacterobilia as a leading cause. Some centers use intraoperative bile duct cultures to guide postoperative antimicrobial prophylaxis. This prospective study evaluates culture differences between traditional bile duct swab versus bile duct aspiration intraoperative samples.

Methods: Prospective patients undergoing pancreatic head resection with both bile duct swab and bile duct aspiration were included. Cultures were reviewed for organism characteristics. Any growth of organisms was considered a positive culture. Bile duct swab yield and characteristics were compared with bile duct aspiration. Postoperative surgical site infection complications were compared to bile duct culture results.

Results: Fifty patients were included. Bile duct aspiration resulted in a significantly higher median number of organisms compared to bile duct swab (6 vs 3; P < .001). There were no differences in the number of patients (37 vs 33) having positive bile duct aspiration and bile duct swab cultures (P = .385). Anaerobic cultures (not possible with bile duct swab) were positive in 21 patients with bile duct aspiration. A total of 37 (74%) patients had preoperative biliary stenting, which highly associated (P < .001) with positive cultures. Bile duct culture organisms correlated with postoperative surgical site infection in 12/17 (71%) patients.

Conclusion: Use of bile duct aspiration improves intraoperative bile duct culture organism yield over bile duct swab and may improve tailoring of antibiotics in patients undergoing pancreatic head resection.
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http://dx.doi.org/10.1016/j.surg.2021.06.013DOI Listing
July 2021

Predicting Adverse Pathologic Features and Clinical Outcomes of Resectable Pancreas Cancer With Preoperative CA 19-9.

Front Oncol 2021 11;11:651119. Epub 2021 May 11.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States.

Background: We evaluated preoperative CA 19-9 levels in patients with resected pancreatic cancer to analyze whether they were predictive of clinical outcomes and could help select patients for additional therapy. We hypothesized that elevated CA 19-9 would be associated with worse pathologic findings and oncologic outcomes.

Methods: This study assessed 509 patients with non-metastatic pancreatic adenocarcinoma who underwent resection at our institution from 1995-2011 and had preoperative CA 19-9 recorded. No patients received neoadjuvant therapy. CA 19-9 level was analyzed as a continuous and a dichotomized (> . ≤ 55 U/mL) variable using logistic and Cox models.

Results: Median follow-up was 7.8 years, and the median age was 66 years (33-90). 64% of patients had elevated preoperative CA 19-9 (median: 141 U/mL), that did not correlate with bilirubin level or tumor size. Most patients had ≥ T3 tumors (72%) and positive lymph nodes (62%). The rate of incomplete (R1 or R2) resection was 19%. Increasing preoperative CA 19-9 was associated with extra-pancreatic extension (p=0.0005), lymphovascular space invasion (p=0.0072), incomplete resection [HR (95% CI) 2.0 (1.2-3.5)], and lower OS [HR = 1.6 (1.3-2.0)]. Each doubling in preoperative CA 19-9 value was associated with an 8.3% increased risk of death [HR = 1.08 (1.02-1.15)] and a 10.0% increased risk of distant recurrence [HR = 1.10 (1.02-1.19)]. Patients classified as non-secretors had comparable outcomes to patients with normal CA 19-9.

Conclusions: Elevated preoperative CA 19-9 level was associated with adverse pathologic features, incomplete resection, and inferior clinical outcomes. Neither tumor size nor bilirubin confound an elevated CA 19-9 level. Preoperative CA 19-9 level may help select patients for additional therapy.
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http://dx.doi.org/10.3389/fonc.2021.651119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147692PMC
May 2021

Molecular Peritoneal Staging for Pancreatic Ductal Adenocarcinoma Using Mutant KRAS Droplet-Digital Polymerase Chain Reaction: Results of a Prospective Clinical Trial.

J Am Coll Surg 2021 Jul 20;233(1):73-80.e1. Epub 2021 May 20.

Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery. Electronic address:

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with predilection for peritoneal dissemination. Accurate peritoneal staging is imperative for treatment recommendations, as one-third of patients develop peritoneal recurrence after resection. Because >90% of PDAC tumors harbor mutant KRAS (mKRAS), we sought to determine feasibility of mKRAS DNA detection in peritoneal lavage (PL) fluid using droplet-digital polymerase chain reaction (ddPCR) via a prospective trial.

Study Design: Patients with nonmetastatic PDAC undergoing staging laparoscopy with PL were included. PL fluid was sent for cytologic examination, CA19-9/CEA levels, and mKRAS ddPCR assay. Clinically positive laparoscopy was defined as gross metastases or positive cytology. PL mKRAS status was compared with gross findings, cytology, and CA19-9/CEA levels.

Results: There were 136 patients enrolled; 70 of 136 (51%) patients received neoadjuvant therapy before PL, and 32 of 136 (24%) patients had clinically positive laparoscopy. Cytology was positive in 17 of 136 (13%) patients, and 22 of 136 (16%) patients had gross metastases. Of patients with gross metastases, only 8 of 22 (36%) had positive cytology; 97 of 136 (71%) patients had mKRAS in PL. PL mKRAS was present in 27 of 32 (84%) clinically positive laparoscopies, with higher mean copy number in clinically positive patients (643 vs 10, p = 0.02). Peritoneal mKRAS was positive in an additional 70 clinically negative patients.

Conclusions: This prospective study establishes the feasibility of PL mKRAS detection. Clinically positive disease was identified in 1 in 4 staging laparoscopies. Although PL mKRAS was highly associated with clinically positive findings, many clinically negative laparoscopies had detectable PL mKRAS, suggesting that standard staging may be inadequate. Longer follow-up will elucidate utility of this promising molecular assay.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.05.009DOI Listing
July 2021

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

Ann Surg 2021 07;274(1):50-56

Southern Illinois University School of Medicine, Departments of Surgery and Medical Education, Springfield, Illinois.

Objective: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities.

Background: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled. The Coronavirus Global Surgical Collaborative sought to formulate, through rigorous scientific methodology, consensus-based recommendations in collaboration with a multidisciplinary group of international experts and policymakers.

Methods: Recommendations were developed following a Delphi process. Domain topics were formulated and subsequently subdivided into questions pertinent to different aspects of surgical care in the COVID-19 crisis. Forty-four experts from 15 countries across 4 continents drafted statements based on the specific questions. Anonymous Delphi voting on the statements was performed in 2 rounds, as well as in a telepresence meeting.

Results: One hundred statements were formulated across 10 domains. The statements addressed terminology, impact on procedural services, patient/staff safety, managing a backlog of surgeries, methods to restart and sustain surgical services, education, and research. Eighty-three of the statements were approved during the first round of Delphi voting, and 11 during the second round. A final telepresence meeting and discussion yielded acceptance of 5 other statements.

Conclusions: The Delphi process resulted in 99 recommendations. These consensus statements provide expert guidance, based on scientific methodology, for the safe resumption of surgical activities during the COVID-19 pandemic.
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http://dx.doi.org/10.1097/SLA.0000000000004674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189258PMC
July 2021

Synchronous resection of colorectal cancer primary and liver metastases: an outcomes analysis.

HPB (Oxford) 2021 Jan 18. Epub 2021 Jan 18.

Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA.

Background: Concurrent resection of the primary cancer and synchronous colorectal cancer liver metastases (CRCLM) was evaluated for differences in outcomes following stratification of both the liver and colorectal resection.

Methods: Consecutive cases of synchronous resection of both the CRC primary and CRCLM were reviewed retrospectively at a single, high-volume institution over a 17-year period (2000-2017).

Results: 273 patients underwent simultaneous resection of CRCLM. The distribution of the primary lesion was similar between the colon (52.4%) and rectum (47.6%), while 46.9% of patients had bilobar liver disease. Major liver/major colorectal resection (n = 24) were significantly more likely to experience colorectal specific morbidity (OR 3.98, 95% CI 1.56-10.15, p = 0.004), liver specific morbidity (OR 7.4, 95% CI 2.22-24.71, p = 0.001), total morbidity (OR 2.91, 95% CI 1.18-7.18, p = 0.020) and 90-day mortality (OR 5.50, 95% CI 1.27-23.81, p = 0.023). Failure to receive adjuvant chemotherapy secondary to postoperative morbidity was associated with significantly worsened survival (HR for death 5.91, 95% CI 1.59-22.01, p = 0.008).

Conclusions: Postoperative morbidity precluding the administration of adjuvant chemotherapy is associated with an increase in mortality. Combining a major liver with major colorectal resection is associated with a significant increase in major morbidity and 90-day mortality, and should be avoided.
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http://dx.doi.org/10.1016/j.hpb.2021.01.002DOI Listing
January 2021

Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery.

Hepatology 2021 May 16;73(5):1956-1966. Epub 2021 Mar 16.

Department of Surgery, HPB Center, Viennese Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria.

Background And Aims: Platelet-stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin's impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection.

Approach And Results: Consecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07-2.31; severe morbidity OR, 1.86; 95% CI, 1.22-2.79; LD OR, 1.96; 95% CI, 1.23-3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03-4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90-day mortality and 1-year overall survival.

Conclusions: We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.
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http://dx.doi.org/10.1002/hep.31601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251772PMC
May 2021

Finding the Balance: General Surgery Resident Versus Fellow Training and Exposure in Hepatobiliary and Pancreatic Surgery.

J Surg Educ 2021 May-Jun;78(3):875-884. Epub 2020 Oct 17.

Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Institutions training both General Surgery (GS) residents and Hepato-Pancreatico-Biliary (HPB) fellows must strive for adequate case volumes for each trainee cohort.

Methods: Six academic years of graduating ACGME Residency and HPB Fellowship Council case logs (July 2011-June 2017) and institutional administrative faculty billing data were examined at a single high-volume center with a formal HPB Surgical Division with both GS Residency and HPB Surgery Fellowship trainees.

Results: During the 6-year period, 7482 operations were performed by HPB faculty (5.5 total full-time equivalent (FTE)) and included 2419 major liver, 375 major biliary, and 1591 major pancreas cases. Residents/fellows performed 1102 (50%)/1101 (50%) of all major liver operations, 165 (49.7%)/163 (50.3%) major biliary operations, and 843 (59.2%)/581 (40.8%) major pancreas operations, with significantly different case mix of pancreas for resident versus fellow, p < 0.0001. The overall relative proportion of total HPB cases performed by residents versus fellows was 53%/47%, respectively, and this was stable over time, with no significant decrease in resident exposure/cases with dedicated HPB fellowship.

Conclusions: Our experience in training both GS residents and HPB fellows with a formal HPB Surgical Division suggests that a high volume HPB Division allows for more than adequate exposure for both groups of trainees.
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http://dx.doi.org/10.1016/j.jsurg.2020.09.002DOI Listing
June 2021

Emergent pancreatectomy for neoplastic disease: outcomes analysis of 534 ACS-NSQIP patients.

BMC Surg 2020 Jul 27;20(1):169. Epub 2020 Jul 27.

Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: While emergent pancreatic resection for trauma has been previously described, no large contemporary investigations into the frequency, indications, and outcomes of emergent pancreatectomy (EP) secondary to complications of neoplastic disease exist. Modern perioperative outcomes data are currently unknown.

Methods: ACS-NSQIP was reviewed for all non-traumatic pancreatic resections (DP - distal pancreatectomy, PD - pancreaticoduodenectomy, or TP- total pancreatectomy) in patients with pancreatico-biliary or duodenal-ampullary neoplasms from 2005 to 2013. Patients treated for complications of pancreatitis were specifically excluded. Emergent operation was defined as NSQIP criteria for emergent case and one of the following: ASA Class 5, preoperative ventilator dependency, preoperative SIRS, sepsis, or septic shock, or requirement of > 4 units RBCs in 72 h prior to resection. Chi-square tests, Fisher's exact tests were performed to compare postoperative outcomes between emergent and elective cases as well as between pancreatectomy types.

Results: Of 21,452 patients who underwent pancreatectomy for neoplastic indications, we identified 534 (2.5%) patients who underwent emergent resection. Preoperative systemic sepsis (66.3%) and bleeding (17.9%) were most common indications for emergent operation. PD was performed in 409 (77%) patients, DP in 115 (21%), and TP in 10 (2%) patients. Overall major morbidity was significantly higher (46.1% vs. 25.6%, p < 0.001) for emergent vs. elective operations. Emergent operations resulted in increased transfusion rates (47.6% vs. 23.4%, p < 0.001), return to OR (14.0% vs. 5.6%, p < 0.001), organ-space infection (14.6 vs. 10.5, p = 0.002), unplanned intubation (9.% vs. 4.1%, p < 0.001), pneumonia (9.6% vs. 4.2%, p < 0.001), length of stay (14 days vs. 8 days, p < 0.001), and discharge to skilled facility (31.1% vs. 13.9%). These differences persisted when stratified by pancreatic resection type. The 30-day operative mortality was higher in the emergent group (9.4%vs. 2.7%, p < 0.001) and highest for emergent TP (20%).

Conclusion: Emergent pancreatic resection is markedly uncommon in the setting of neoplastic disease. Although these operations result in increased morbidity and mortality compared to elective resections, they can be life-saving in specific circumstances. The results of this large series of modern era national data may assist surgeons as well as patients and their families in making critical decisions in select cases of acutely complicated neoplastic disease.
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http://dx.doi.org/10.1186/s12893-020-00822-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385869PMC
July 2020

Significance of proximal ductal margin status after resection of hilar cholangiocarcinoma.

HPB (Oxford) 2021 Jan 25;23(1):109-117. Epub 2020 Jun 25.

Department of Subspecialty General Surgery, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address:

Background: The impact of additional resection for positive proximal bile duct margins during hepatic resection of hilar cholangiocarcinoma (HCCA) on survival and disease progression remains unclear. We asked how re-resection of positive proximal bile duct margins affected outcomes.

Methods: Patients undergoing resection between 1993-2017 were reviewed. Both frozen section and final margin status were reviewed. Overall survival was the primary outcome.

Results: 153 patients underwent surgical resection for HCCA. Median survival (months) for initial margin negative (M-), margin-positive to margin-negative (M+/M-) and margin-positive to margin-positive (M+/M+) was 45, 33, and 35 months respectively. Nodal metastases increased with margin positivity: 32% with M-, 49% with M+/M- and 63% with M+/M+ (p = 0.016). Local/regional progression more frequently occurred in M+/M- (27.3%) and M+/M+ (33.3%) patients (M+/M- vs. M-: p = 0.41, M+/M+ vs. M-: p = 0.27). Patients receiving postoperative chemotherapy were 33% M-, 46% M+/M- and 63% in M+/M+. Postoperative radiation was used in 13% of M-, 31% of M+/M- and 63% of M+/M+. Most frequent initial recurrences were within the liver and hepaticojejunostomy site.

Conclusion: Competing risk for systemic disease based on primary characteristics of HCCA outweighs the impact of re-resection to achieve R0 status. Improved survival will likely depend on future regional and systemic therapy.
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http://dx.doi.org/10.1016/j.hpb.2020.05.002DOI Listing
January 2021

Genetics of Hepatocellular Carcinoma: Approaches to Explore Molecular Diversity.

Hepatology 2021 Jan 8;73 Suppl 1:14-26. Epub 2020 Dec 8.

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Université Paris 13, Functional Genomics of Solid Tumors Laboratory, Paris, France.

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http://dx.doi.org/10.1002/hep.31394DOI Listing
January 2021

Distinct classes of multi-subunit heterogeneity: analysis using Fourier Transform methods and native mass spectrometry.

Analyst 2020 Jul 27;145(13):4688-4697. Epub 2020 May 27.

Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, OR 97403-1253, USA.

Native electrospray mass spectrometry is a powerful method for determining the native stoichiometry of many polydisperse multi-subunit biological complexes, including multi-subunit protein complexes and lipid-bound transmembrane proteins. However, when polydispersity results from incorporation of multiple copies of two or more different subunits, it can be difficult to analyze subunit stoichiometry using conventional mass spectrometry analysis methods, especially when m/z distributions for different charge states overlap in the mass spectrum. It was recently demonstrated by Marty and co-workers (K. K. Hoi, et al., Anal. Chem., 2016, 88, 6199-6204) that Fourier Transform (FT)-based methods can determine the bulk average lipid composition of protein-lipid Nanodiscs assembled with two different lipids, but a detailed statistical description of the composition of more general polydisperse two-subunit populations is still difficult to achieve. This results from the vast number of ways in which the two types of subunit can be distributed within the analyte ensemble. Here, we present a theoretical description of three common classes of heterogeneity for mixed-subunit analytes and demonstrate how to differentiate and analyze them using mass spectrometry and FT methods. First, we first describe FT-based analysis of mass spectra corresponding to simple superpositions, convolutions, and multinomial distributions for two or more different subunit types using model data sets. We then apply these principles with real samples, including mixtures of single-lipid Nanodiscs in the same solution (superposition), mixed-lipid Nanodiscs and copolymers (convolutions), and isotope distribution for ubiquitin (multinomial distribution). This classification scheme and the FT method used to study these analyte classes should be broadly useful in mass spectrometry as well as other techniques where overlapping, periodic signals arising from analyte mixtures are common.
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http://dx.doi.org/10.1039/d0an00726aDOI Listing
July 2020

En Bloc Celiac Axis Resection for Pancreatic Cancer: Classification of Anatomical Variants Based on Tumor Extent.

J Am Coll Surg 2020 07 15;231(1):8-29. Epub 2020 May 15.

Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic College of Medicine, Rochester, MN.

Background: En bloc celiac axis resection (CAR) for pancreatic cancer is considered increasingly after modern neoadjuvant chemotherapy (NAC). Appleby and distal pancreatectomy with CAR are anatomically inaccurate terms, as tumors can extend beyond celiac axis proper, requiring concurrent resection of the proper hepatic artery and/or superior mesenteric artery.

Study Design: A 3-level classification for CAR (class 1, 2, or 3) was developed after retrospective review of an arterial resection database describing anatomical variants that dictate pancreatectomy-type, formal arterial revascularization, and gastric preservation. Perioperative and oncologic outcomes were assessed.

Results: Of 90 CARs for pancreatic cancer, 89% patients received NAC, 35% requiring chemotherapeutic switch. There were 41 class 1, 33 class 2, and 16 class 3 CARs, with arterial and venous revascularization performed 62% and 66%, respectively. Ninety-day mortality decreased to 4% in the last 50 cases (p = 0.035); major morbidity was unchanged (55%). Any hepatic or gastric ischemia occurred in 20% and 10% patients, respectively, and arterial revascularization was protective. R0 resection rate (88%) was associated with chemoradiation (p = 0.004). Median overall survival was 36.2 months, superior with NAC (8.0 vs. 43.5 months). Predictors of survival after NAC included chemotherapy duration, carbohydrate antigen 19-9 response, pathologic response, and lymph node status. Major pathologic response (p = 0.036) and extended duration NAC (p = 0.007) were independent predictors on multivariate analysis.

Conclusions: Current terminology for CAR inadequately describes all operative variants. Our classification, based on the largest single-center series, allows complex operative planning and standardized reporting across institutions. Extent of arterial involvement determines pancreatectomy type, need for arterial revascularization, and likelihood of gastric preservation. Operative mortality has improved, morbidity remains significant, and survival favorable after extended NAC with associated pathologic responses; given these factors, CAR should only be considered in fit patients with objective NAC responses at specialized centers.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.05.005DOI Listing
July 2020

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine.

JHEP Rep 2020 Apr 16;2(2):100068. Epub 2020 Jan 16.

Department of Surgery, Mayo Clinic, Rochester, MN.

Background & Aims: Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog.

Methods: With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq).

Results: Between October 2013 and January 2018, 87 patients with histologically confirmed biliary tract carcinomas were enrolled. Of the 87 patients, 47 validated PDX models were successfully generated. The majority of the PDX models were created from surgical resection specimens (n = 44, 94%), which were more likely to successfully engraft when compared to radiologic biopsies ( = 0.03). Histologic recapitulation of original patient tumor morphology was observed in all xenografts. Successful engraftment was an independent predictor for worse recurrence-free survival. MPseq showed genetically diverse tumors with frequent alterations of . Sequencing also identified worse survival in patients with tumors containing tetraploid genomes.

Conclusions: This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients.

Lay Summary: Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.
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http://dx.doi.org/10.1016/j.jhepr.2020.100068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066236PMC
April 2020

Effect of vessel preservation on splenic volume and function in patients with spleen preserving distal pancreatectomies.

HPB (Oxford) 2020 11 17;22(11):1563-1568. Epub 2020 Feb 17.

Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Spleen preservation during distal pancreatectomy (SpDP) can be accomplished by a variety of surgical approaches, but the impact on spleen function is unknown. This study aimed to compare spleen volume, function and complications between patients who underwent vessel sparing (VSDP) vs. vessel ligating (Warshaw, WDP) SpDP.

Methods: All patients who underwent SpDP at the Toronto General Hospital from 2006 to 2015 were included. Primary outcomes were pre- and post-operative spleen volumes and contrast enhancement on CT, hematologic parameters, and spleen-related complications.

Results: 82 patients underwent SpDP with median follow up of 20.4 months. Splenic volumes were able to be calculated on 44 patients (VSDP n = 8, WDP n = 36). There was no difference between WDP and VSDP in operative duration, blood loss, hospital length of stay, or Clavien-Dindo ≥3 complication rate. Spleen volumes did not differ from baseline in either group. On postoperative imaging more WDP patients had areas of splenic hypoperfusion (p = 0.032). These differences resolved by 3 months after surgery, there were no instances of long term infectious or bleeding complications related to poor splenic function or gastric varices.

Conclusion: Both WDP and VSDP achieve splenic preservation. Neither technique resulted in clinically apparent spleen related complications. There is no difference in splenic volume and function in the short/long term.
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http://dx.doi.org/10.1016/j.hpb.2020.01.012DOI Listing
November 2020

A Novel Clinically Based Staging System for Gallbladder Cancer.

J Natl Compr Canc Netw 2020 02;18(2):151-159

Department of Oncology, Mayo Clinic, Rochester, Minnesota.

Background: Current staging systems for gallbladder cancer (GBC) are primarily based on surgical pathology and therefore are not relevant for unresectable patients and those undergoing neoadjuvant chemotherapy.

Methods: Patients with a confirmed diagnosis of GBC managed at a tertiary referral center (2000-2016) were included. Independent predictors of overall survival (OS) were identified using multivariable analysis (MVA). A combination of these variables was then assessed to identify a set of factors that provided maximal accuracy in predicting OS, and a nomogram and a new staging system were created based on these factors. Harrell's C-statistic was calculated to evaluate the predictive accuracy of the nomogram and staging system.

Results: A total of 528 patients were included in the final analysis. On MVA, factors predictive of poor OS were older age, ECOG performance status, hemoglobin level <9 g/dL, presence of metastases, and alkaline phosphatase (ALP) level >200 U/L. A nomogram and a 4-tier staging system predictive of OS were created using age at diagnosis, ECOG status, tumor size, presence or absence of metastasis, and ALP level. The C-statistic for this novel staging system was 0.71 compared with 0.69 for the TNM staging system (P=.08). In patients who did not undergo surgery, the C-statistics of the novel and TNM staging systems were 0.60 and 0.51, respectively (P<.001).

Conclusions: We created a novel, clinically based staging system for GBC based on nonoperative information at the time of diagnosis that was superior to the TNM staging system in predicting OS in patients who did not undergo surgery, and that performed on par with TNM staging in surgical patients.
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http://dx.doi.org/10.6004/jnccn.2019.7357DOI Listing
February 2020

Impact of resection margin status on survival in pancreatic cancer patients after neoadjuvant treatment and pancreatoduodenectomy.

Surgery 2020 05 25;167(5):803-811. Epub 2020 Jan 25.

Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA. Electronic address:

Background: Resection margin status has been recognized as an independent prognostic factor on overall survival in pancreatic cancer patients undergoing surgical resection. However, its impact after neoadjuvant treatment remains uncertain.

Methods: We analyzed 305 patients with resectable or borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatoduodenectomy at 3 tertiary referral centers between 2010 and 2017. Positive resection margin was defined as 1 or more cancer cells at any margin. Overall survival was measured from the date of surgery until death or last follow-up.

Results: One hundred and seventy-eight patients received neoadjuvant chemotherapy and 127 received neoadjuvant chemoradiotherapy. The median overall survival was 29.8 months. The 1-, 3-, and 5-year overall survival rates were 79.2%, 44.0%, and 23.5%, respectively. Negative margin was achieved in 275 (90.2%) patients. Negative margin resection patients had a significantly longer overall survival than positive resection margin patients (31.3 vs 16.3 months, P < .001). In univariate analyses, overall survival was associated with age, margin status, histologic grade, ypT, number of positive lymph nodes, perineural invasion, treatment effect, postoperative carbohydrate antigen 19-9, and adjuvant therapy. Positive margin resection, poorly differentiated carcinoma, treatment effect score of 3, postoperative carbohydrate antigen 19-9 of 37 U/mL or higher, and lack of adjuvant therapy were predictive of poor overall survival in multivariate Cox regression analysis.

Conclusion: Margin status was an independent predictor of overall survival in patients treated with neoadjuvant therapy and pancreatoduodenectomy, supporting the use of a negative margin resection as a surrogate of adequate oncological resection in this setting. Our findings may also have significant implications for patient stratification in future randomized trials.
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http://dx.doi.org/10.1016/j.surg.2019.12.008DOI Listing
May 2020

Novel staging system using carbohydrate antigen (CA) 19-9 in extra-hepatic cholangiocarcinoma and its implications on overall survival.

Eur J Surg Oncol 2020 05 11;46(5):789-795. Epub 2020 Jan 11.

Department of Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: CA19-9 elevation has shown to be associated with poor prognosis in extrahepatic cholangiocarcinoma (ECCA). However, the role of CA19-9 in staging of ECCA has not been evaluated. We hypothesized that CA19-9 elevation is a marker of aggressive biology in ECCA and that inclusion of CA19-9 in the staging system may improve overall survival (OS) discrimination.

Methods: Patients with ECCA whose CA19-9 levels, irrespective of surgical status, were reported to the National Cancer Database (2004-2015) were included. The patients were classified based on their CA19-9 levels and a new staging system was proposed. Net reclassification improvement (NRI) model was used to assess the predictive improvement in the proposed survival model as compared to AJCC-TNM staging.

Results: Of the 2100 patients included in the study, 626 (32%) and 1474 (68%) had normal and elevated CA19-9 levels (>38 U/ml), respectively. Median OS was lower among patients with elevated CA19-9 level compared to those with CA19-9 level ≤38 U/ml (8.5 vs 16 months, p < 0.01). On multivariate analysis, CA19-9 elevation independently predicted poor prognosis [HR:1.72 (1.46-2.02); p < 0.01] with similar impact as node-positivity, positive resection margins and non-receipt of chemotherapy. We developed a new staging system by incorporating CA19-9 into the 7th edition AJCC TNM staging system. NRI of 46% (95%CI: 39-57%) indicates that the new staging system is substantially effective at re-classifying events at 12 months as compared to AJCC 7th edition.

Conclusion: Elevated CA19-9 was found to be an independent risk factor for mortality in ECCA and its inclusion in the proposed staging system improved OS discrimination.
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http://dx.doi.org/10.1016/j.ejso.2020.01.016DOI Listing
May 2020

Acute and early EUS-guided transmural drainage of symptomatic postoperative fluid collections.

Gastrointest Endosc 2020 05 13;91(5):1085-1091.e1. Epub 2019 Dec 13.

Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: EUS-guided postoperative drainage (EUS-POD) of postoperative fluid collections (POFCs) is typically delayed until a thick wall has formed to optimize safety. Thus, percutaneous drainage is the mainstay of early POFC management. The primary aim of this study was to compare technical and clinical success and adverse event (AE) rate between early (0-30 days postoperative) compared with delayed (>30 days) EUS-POD. The secondary aim was to determine predictors for clinical success and AE rate associated with early compared with delayed EUS-POD.

Methods: This was a retrospective analysis of consecutive patients undergoing EUS-POD between November 2013 and November 2018 at a single tertiary academic center. Demographic, procedural, and outcomes data were recorded. Clinical success was defined as resolution of symptoms and the fluid collection on cross-sectional imaging without recurrence after transluminal stent removal.

Results: Seventy-five patients underwent EUS-POD; 42 (56%) were early, of whom 20 were acute. Sixty-three patients (84%) had undergone distal pancreatectomy. Technical success was 100%, and clinical success was achieved in 70 patients (93%) after a mean 2.2 procedures (range, 1-5). Prior percutaneous drainage had been performed in 13 patients (17.3%). Both acute and early drainage versus delayed EUS-POD demonstrated similar rates of clinical success (95% and 93% vs 94%, P = .99) and AEs (21.4% and 15% vs 30.3%, P = .43). Necrosectomy was required less often in the early versus the delayed group. No predictors of clinical success were identified. Early EUS-POD was not a predictor of AEs (P = .65). Infection and collection size >10 cm correlated with increased AE risk (P = .048 and .007, respectively).

Conclusions: Early and even acute EUS-POD of POFCs appears to be technically feasible, clinically effective, and safe. EUS-POD should be considered for definitive management of early symptomatic POFCs.
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http://dx.doi.org/10.1016/j.gie.2019.11.045DOI Listing
May 2020

Preoperative opioid use is associated with increased length of stay after pancreaticoduodenectomy.

HPB (Oxford) 2020 07 12;22(7):1074-1081. Epub 2019 Dec 12.

Mayo Clinic Rochester, Department of Surgery, USA. Electronic address:

Background: Preoperative opioid use in patients undergoing low complexity operations has been associated with increased complications, but its relationship to procedures of greater complexity is unclear. We aimed to assess this impact on outcomes following pancreaticoduodenectomy (PD).

Methods: A single institution, retrospective cohort of adults undergoing elective PD for cancer (1/2009-9/2015). Preoperative opioid users were defined as patients documented as taking opioids up to 90 days preoperatively. Discharge prescriptions were converted into Oral Morphine Equivalents (OME) and ten-point pain scores were abstracted. Univariate and multivariable analyses compared outcomes of naïve and preoperative opioid users overall and for laparoscopic vs open surgery.

Results: Of 661 PD patients, 131 (19.8%) were preoperative opioid users. These patients had greater mean pain scores over the first three days after surgery (3.4 ± 1.6, vs 2.8 ± 1.4, p < 0.001), max pain (7.9 ± 1.9 vs 7.2 ± 2.0, p < 0.001), and discharge pain (2.3 ± 1.9 vs 1.8 ± 1.6, p = 0.01) than naïve patients. Preoperative opioid users received more opioids at discharge (mean 496 ± 764 OME) than naïve (320 ± 489 OME, p = 0.03). Thirty-day refill rates were 12.6% (19.1% preoperative vs 10.9% naïve, p = 0.02). After controlling for tumor type, pancreas texture, and duct size, naïve patients had similar odds of clinically significant post-operative pancreatic fistulas (grade B or C) (OR 1.13, p = 0.68) and delayed gastric emptying (OR 1.05, p = 0.87). After controlling for age and complications, preoperative opioid use was associated with increased odds of LOS ≥9 days (OR 1.59, p = 0.04).

Conclusion: Following PD, preoperative opioid users had worse pain scores, received more opioids at discharge, refilled prescriptions more frequently, and were more likely to have prolonged LOS. As most opioid utilization research has been focused on low complexity surgery, additional work aimed at optimizing opioid use in complex oncologic operations is warranted.
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http://dx.doi.org/10.1016/j.hpb.2019.11.010DOI Listing
July 2020

A Canadian strategy for surgical quality improvement

Can J Surg 2019 12 1;62(6):E16-E18. Epub 2019 Dec 1.

From the University of Toronto, Toronto, Ont. (Urbach, Wei, McLeod); the University of British Columbia, Vancouver, BC (Karimuddin, Hameed); the University of Manitoba, Winnipeg, Man. (Zabolotny); the Canadian Medical Protective Association, Ottawa, Ont. (Lefebvre); Dalhousie University, Halifax, NS (Walsh); McGill University, Montreal, Que. (Fata, Chaudhury); and the Mayo Clinic, Rochester, Minn. (Cleary).

Summary: The Canadian Association of General Surgeons (CAGS) Board of Directors hosted a symposium to develop a Canadian strategy for surgical quality and safety at its mid-term meeting on Feb. 24, 2018. The following 6 principles outline the consensus of this symposium, which included diverse stakeholders and surgeon leaders across Canada: 1) a Canadian quality-improvement strategy for surgery is needed; 2) quality improvement requires continuous, active and intentional effort; 3) outcome measurement alone will not drive improvement; 4) increased focus on standardization and process improvement is necessary; 5) new, large electronic medical record systems pose challenges as well as benefits in Canadian hospitals; and 6) surgeons in remote and rural hospitals must be engaged using tailored approaches.
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http://dx.doi.org/10.1503/cjs.019318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877378PMC
December 2019

Transcriptional and posttranscriptional regulation of the locus of enterocyte effacement in Escherichia albertii.

Microb Pathog 2019 Oct 20;135:103643. Epub 2019 Jul 20.

Department of Biology, Saint Joseph's University, 5600 City Avenue, Philadelphia, 19131, PA, USA. Electronic address:

The diarrheic bacterium Escherichia albertii is a recent addition to the attaching and effacing (A/E) morphotype of pathogens. A/E pathogens cause disease by tightly attaching to intestinal cells, destroying their actin-rich microvilli, and triggering re-localization and repolymerization of actin at the bacterial-host interface to form actin-filled membranous protrusions, termed A/E lesions, beneath the adherent bacterium. The locus of enterocyte effacement (LEE) is required for the biogenesis of these lesions. Whereas regulation of the LEE has been intensively investigated in EPEC and EHEC, it remains cryptic in E. albertii. In this study we characterized the very first transcriptional and posttranscriptional regulators of the LEE in this emerging pathogen. Our results suggest that Ler and GrlA globally activate transcription from the LEE, whereas GrlR negatively regulates the LEE. Additionally, we demonstrate that the RNA chaperone Hfq posttranscriptionally represses the LEE by specifically targeting the 5' UTR of grlR. In summary, our findings provide the very first glimpse of the regulatory landscape of the LEE in E. albertii - a bacterium that has been implicated in multiple diarrheal outbreaks worldwide.
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http://dx.doi.org/10.1016/j.micpath.2019.103643DOI Listing
October 2019

Early-onset gastric cancer is a distinct disease with worrisome trends and oncogenic features.

Surgery 2019 10 20;166(4):547-555. Epub 2019 Jul 20.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN. Electronic address:

Background: Overall the incidence of gastric cancer is declining in the United States; however, the incidence of early-onset gastric cancer is increasing. We sought to elucidate clinical and genomic characteristics and risk factors for early-onset gastric cancer compared with late-onset gastric cancer.

Methods: We utilized the Surveillance, Epidemiology, and End Results database (1973-2015), the Behavioral Risk Factor Surveillance Survey, and The Cancer Genome Atlas to characterize early-onset gastric cancer.

Results: The incidence of early-onset gastric cancer increased during the study period and now comprises >30% of all gastric cancer in the United States. Early-onset gastric cancer was associated with higher grade (55.2 vs 46.9%), signet-ring cells (19.0 vs 10.4%), diffuse histology (25.7 vs 15.0%), and metastatic disease (49.5 vs 40.9%, all P < .01) compared with late-onset gastric cancer. Early-onset gastric cancer was more likely to be Epstein-Barr virus (7.7 vs 5.1%) or genomically stable (22.5 vs 8.1%) subtype, whereas late-onset gastric cancer was more likely to be microsatellite instability subtype (18.6 vs 5.6%; all P < .01). Risk factors for gastric cancer were less correlated with early-onset gastric cancer compared with late-onset gastric cancer.

Conclusion: The incidence of early-onset gastric cancer has been steadily increasing in the United States, comprising >30% of new gastric cancer cases today. Early-onset gastric cancer is genetically and clinically distinct from traditional gastric cancer. Additional investigations are warranted to better understand this alarming phenomenon.
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http://dx.doi.org/10.1016/j.surg.2019.04.036DOI Listing
October 2019

Survival and prognostic factors in patients with pancreatic squamous cell carcinoma.

Eur J Surg Oncol 2019 Sep 15;45(9):1700-1705. Epub 2019 May 15.

Department of Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Objectives: Squamous cell carcinoma (SCC) of pancreas is rare entity with poorly defined prognostic factors and therapeutic outcomes. We sought to determine the overall survival (OS) and prognostic factors of patients with pancreatic SCC using National Cancer Database (NCDB) (2004-15).

Methods: Kaplan-Meier method and log-rank test were used to perform OS analysis. Propensity-matched analysis was used to compare the OS of pancreatic SCC and adenocarcinoma.

Results: Of the 515 cases included in our analysis, 46% were female. Approximately half of the cohort (48%) received chemotherapy or radiation therapy or both. Twenty six percent (33/125) of stage I and II disease (localized disease), 11% (8/72) of stage III, and 2% (6/318) of stage IV disease underwent surgical resection of the primary tumor. Median OS for the entire cohort was 4 months and was significantly higher in patients who underwent surgical resection of the primary tumor (17 vs 4 months, p < 0.001). In localized disease, adjuvant chemotherapy was not associated with improved OS in early stage disease (20 vs 24 months, p = 0.60). Stage IV patients treated with chemotherapy had a better OS than those without (5 vs 2 months, p < 0.0001). Propensity matched analysis demonstrated no significant differences in median OS between pancreatic adenocarcinoma (4.8 months) and SCC (4 months, p = 0.09).

Conclusions: Pancreatic SCC had a diverse OS that varied significantly according to increasing age (>70 years) and stage of the disease at presentation (p < 0.01). Surgical resection of primary tumor was associated with longer OS in stages I-II, whereas chemotherapy was associated with longer OS in stage IV disease.
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http://dx.doi.org/10.1016/j.ejso.2019.05.011DOI Listing
September 2019

Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline/Locally Advanced Pancreatic Cancer.

Ann Surg 2021 02;273(2):341-349

Division of Medical Oncology.

Objective: To identify predictive factors associated with operative morbidity, mortality, and survival outcomes in patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) undergoing total neoadjuvant therapy (TNT).

Background: The optimal preoperative treatment sequencing for BR/LA PDA is unknown. TNT, or systemic chemotherapy followed by chemoradiation (CRT), addresses both occult metastases and positive margin risks and thus is a potentially optimal strategy; however, factors predictive of perioperative and survival outcomes are currently undefined.

Methods: We reviewed our experience in BR/LA patients undergoing resection from 2010 to 2017 following TNT assessing operative morbidity, mortality, and survival in order to define outcome predictors and response endpoints.

Results: One hundred ninety-four patients underwent resection after TNT, including 123 (63%) BR and 71 (37%) LA PDAC. FOLFIRINOX or gemcitabine along with nab-paclitaxel were used in 165 (85%) and 65 (34%) patients, with 36 (19%) requiring chemotherapeutic switch before long-course CRT and subsequent resection. Radiologic anatomical downstaging was uncommon (28%). En bloc venous and/or arterial resection was required in 125 (65%) patients with 94% of patients achieving R0 margins. The 90-day major morbidity and mortality was 36% and 6.7%, respectively. Excluding operative mortalities, the median, 1-year, 2-year, and 3-year recurrence-free survival (RFS) [overall survival (OS)] rates were 23.5 (58.8) months, 65 (96)%, 48 (78)%, and 32 (62)%, respectively. Radiologic downstaging, vascular resection, and chemotherapy regimen/switch were not associated with survival. Only 3 factors independently associated with prolonged survival, including extended duration (≥6 cycles) chemotherapy, optimal post-chemotherapy CA19-9 response, and major pathologic response. Patients achieving all 3 factors had superior survival outcomes with a survival detriment for each failing factor. In a subset of patients with interval metabolic (PET) imaging after initial chemotherapy, complete metabolic response highly correlated with major pathologic response.

Conclusion: Our TNT experience in resected BR/LA PDAC revealed high negative margin rates despite low radiologic downstaging. Extended duration chemotherapy with associated biochemical and pathologic responses highly predicted postoperative survival. Potential modifications of initial chemotherapy treatment include extending cycle duration to normalize CA19-9 or achieve complete metabolic response, or consideration of chemotherapeutic switch in order to achieve these factors may improve survival before moving forward with CRT and subsequent resection.
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http://dx.doi.org/10.1097/SLA.0000000000003284DOI Listing
February 2021

Minimally Invasive Management of Secondary Liver Cancer.

Surg Oncol Clin N Am 2019 04 7;28(2):229-241. Epub 2019 Jan 7.

Mayo Clinic, Division of Surgery, Department of Hepatobiliary and Pancreas Surgery 200 First Street South West, Rochester, MN 55905, USA. Electronic address:

Laparoscopic liver surgery for secondary liver cancer is increasing. The most common indications are colorectal cancer liver metastases followed by adenocarcinoma metastases from other solid organs, such as breast, pancreatic neuroendocrine, and other gastrointestinal tract cancers. This article provides a comprehensive review of crucial concepts when managing secondary liver cancer minimally invasively, a summary of the up-to-date literature, and a discussion of the development of the application of this technique over time.
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http://dx.doi.org/10.1016/j.soc.2018.11.003DOI Listing
April 2019

Management and surveillance of non-functional pancreatic neuroendocrine tumours: Retrospective review.

Pancreatology 2019 Mar 18;19(2):360-366. Epub 2019 Feb 18.

Division of General Surgery, University of Toronto, Toronto, ON, Canada; Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA; Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours.

Methods: A retrospective chart review of patients with non-functional pancreatic neuroendocrine tumours initially managed non-operatively at a single institution was performed. Patients were identified through a search of radiologic reports, and individuals with ≥2 cross-sectional imaging studies performed >6 months apart from Jan. 1, 2000 to Dec. 31, 2013 were included. Data on tumour size, radiologic characteristics at diagnosis, interval radiologic growth, and surgical outcomes were recorded.

Results: Over the thirteen-year study period, 95 patients met inclusion criteria and were followed radiologically for a median of 36 months (18-69 months). Median initial tumour size on first imaging was 14.0 mm (IQR 10-19 mm). Median overall tumour growth rate was 0.03 mm/month (IQR: 0.00-0.14 mm/month). There was no significant relationship between initial tumour size and growth rate for tumours ≤ 2 cm or for lesions between 2 and 4 cm. Thirteen (14%) patients initially managed non-operatively underwent resection during the follow-up period. Reasons for surgery included interval tumour growth, patient anxiety or preference, or diagnostic uncertainty. Median time to surgery was 14 months (IQR 8-19 months). No patients progressed beyond resectability or developed metastatic disease during the observation period.

Conclusion: For patients with sporadic, small, non-functional pancreatic neuroendocrine tumours, radiologic surveillance appears to be a safe initial approach to management.
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http://dx.doi.org/10.1016/j.pan.2019.02.008DOI Listing
March 2019

Effect of portal vein embolization on treatment plan prior to major hepatectomy for hepatocellular carcinoma.

HPB (Oxford) 2019 08 20;21(8):1072-1078. Epub 2019 Feb 20.

Division of General Surgery, Department of Surgery, Toronto, Canada; Department of Surgery, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Portal vein embolization (PVE) is used before major hepatectomy for hepatocellular carcinoma (HCC) to increase future liver remnant (FLR) volume. However, this may increase tumour growth rate, leading to more extensive resections. This study aimed to determine the effect of tumour growth, following PVE, on treatment plan.

Method: Retrospective cohort study conducted on patients treated from 2008 to 2015 with PVE before major hepatectomy for HCC. Liver and tumour volumetry was performed on pre- and post-PVE CT scans. Image-based and actioned plans were compared before and after PVE.

Results: Thirty-one patients received PVE. Non-tumour total liver volume decreased (median 1440 to 1394 cm; p = 0.031), while tumour (median 161-240 cm; p < 0.001) and FLR volumes (median 430-574 cm; p < 0.001) increased. The treatment plan changed in 15/31 patients: more extensive resection (n = 6), less extensive resection (n = 1), no resection as scheduled (n = 8). Tumour progression accounted for a clinically relevant change in treatment plan in 8/31 patients.

Conclusion: Following PVE in the setting of HCC, tumour progression accounts for a change in treatment plan in approximately a quarter of patients. Further research is warranted to determine whether additional liver directed therapy should routinely be used to slow the growth of HCC post-PVE.
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http://dx.doi.org/10.1016/j.hpb.2018.12.009DOI Listing
August 2019

Liberating Native Mass Spectrometry from Dependence on Volatile Salt Buffers by Use of Gábor Transform.

Chemphyschem 2019 02 30;20(4):519-523. Epub 2019 Jan 30.

Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, OR 97403-1253, USA.

Volatile salts, such as ammonium acetate, are commonly used in buffers for the analysis of intact proteins and protein complexes in native electrospray ionization mass spectrometry. Although these solutions are not technically buffers near pH 7, the volatile nature of the salt minimizes ion adduction to proteins upon transfer to vacuum. Conversely, common biochemical salt buffers, such as Tris/NaCl, are not traditionally used in native mass spectrometry because of the tendency of sodium and other ions to adduct to proteins or form large cluster ions, severely frustrating accurate mass assignment. Here, we demonstrate a Gábor transform method for extracting signal from native-like protein ions even in the presence of a large salt-cluster background. We further show the utility of this method in characterizing polymers and show that the measured average mass of long-chain polyethylene glycol ions from a commercial polymer sample is ∼30 % higher than the manufacturer-estimated average mass. It is expected that this method will enable more widespread use of conventional biochemical buffers in native mass spectrometry and decrease dependence on volatile salts.
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http://dx.doi.org/10.1002/cphc.201900022DOI Listing
February 2019
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