Publications by authors named "David M Nagorney"

200 Publications

Safety and Outcomes of Combined Pancreatic and Hepatic Resections for Metastatic Pancreatic Neuroendocrine Tumors.

Ann Surg Oncol 2022 Jun 22. Epub 2022 Jun 22.

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

Background: Approximately 40-50% of patients with pancreatic neuroendocrine tumors (pNETs) initially present with distant metastases. Little is known about the outcomes of patients undergoing combined pancreatic and hepatic resections for this indication.

Methods: Patients who underwent hepatectomy for metastatic pNETs at Mayo Clinic Rochester from 2000 to 2020 were retrospectively reviewed. Major pancreatectomy was defined as pancreaticoduodenectomy or total pancreatectomy, and major hepatectomy as right hepatectomy or trisegmentectomy. Characteristics and outcomes of patients who underwent pancreatectomy with simultaneous hepatectomy were compared with those of patients who underwent isolated hepatectomy (with or without prior history of pancreatectomy).

Results: 205 patients who underwent hepatectomy for metastatic pNETs were identified: 131 underwent pancreatectomy with simultaneous hepatectomy and 74 underwent isolated hepatectomy. Among patients undergoing simultaneous hepatectomy, 89 patients underwent minor pancreatectomy with minor hepatectomy, 11 patients underwent major pancreatectomy with minor hepatectomy, 30 patients underwent minor pancreatectomy with major hepatectomy, and 1 patient underwent major pancreatectomy with major hepatectomy. Patients undergoing simultaneous hepatectomy had more numerous liver lesions (10 or more lesions in 54% vs. 34%, p = 0.008), but the groups were otherwise similar. Rates of any major complications (31% versus 24%, p = 0.43), hepatectomy-specific complications such as bile leak, hemorrhage, and liver failure (0.8-7.6% vs. 1.4-12%, p = 0.30-0.99), and 90-day mortality (1.5% vs. 2.7%, p = 0.62) were similar between the two groups. 5-year overall survival was 64% after combined resections and 65% after isolated hepatectomy (p = 0.93).

Conclusion: For patients with metastatic pNETs, combined pancreatic and hepatic resections can be performed with acceptable morbidity and mortality in selected patients at high-volume institutions.
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http://dx.doi.org/10.1245/s10434-022-12029-7DOI Listing
June 2022

Hepatocellular carcinoma as predominant cancer subgroup accounting for sex differences in post-hepatectomy liver failure, morbidity and mortality.

HPB (Oxford) 2022 Feb 26. Epub 2022 Feb 26.

Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria. Electronic address:

Background: Experimental evidence suggests sex dependent differences in liver regeneration. Limited evidence is available examining sex differences in post-hepatectomy liver failure (PHLF) and postoperative outcomes. Our aim was to assess the influence of sex on the outcomes after liver resection.

Methods: The hepatectomy targeted National Surgical Quality Improvement Program (NSQIP) database was assessed for associations between sex and outcomes.

Results: A total of 13,401 patients underwent elective hepatic resection between 2014-2017. PHLF was highest among male patients with hepatocellular carcinoma (HCC) (OR = 2.81,95%CI:1.40-5.62). Male sex was independently associated with increased PHLF (OR = 1.47,95%CI:1.15-1.88), major complications (OR = 1.25,95%CI:1.08-1.45), mortality (OR = 1.61,95%CI:1.03-2.50), and if only major resections were assessed (OR = 1.38,95%CI:1.03-1.84). Diagnosis specific subgroup analyses revealed that effects of sex were predominantly HCC associated.

Conclusions: This is the largest series investigating the effects of gender on outcomes after hepatic resection. We documented that women undergoing liver resection have significantly lower risk of PHLF. This difference seemed influenced by the striking increase of PHLF in male HCC patients. These hypothesis suggest that sex might play a role in preoperative risk stratification.
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http://dx.doi.org/10.1016/j.hpb.2022.02.009DOI Listing
February 2022

Contemporary outcomes of pancreaticoduodenectomy for benign and precancerous cystic lesions.

HPB (Oxford) 2022 Jan 23. Epub 2022 Jan 23.

Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

Background: The decision to undertake pancreaticoduodenectomy for benign and precancerous lesions has historically relied on outcomes data from operations for cancer. We aimed to describe risks for these specific patients and identify the highest risk groups.

Methods: The ACS-NSQIP pancreatic targeted data was queried for pancreaticoduodenectomies for benign and pre-cancerous neoplasms from 2014 to 2018. Baseline characteristics, operative techniques and outcomes were examined. Multivariate regression was performed to identify predictors of major complications.

Results: 748 patients underwent pancreaticoduodenectomy for (n = 541,72.3%) IPMN, (n = 87,11.6%) MCN, (n = 78,10.4%) serous cystadenoma, and (n = 42,5.6%) solid pseudopapillary neoplasm. Median LOS was 8 days. Major complications (n = 135,18.0%), non-home discharges (n = 83,11.1%) and readmissions (n = 153,20.5%) occurred frequently. In patients ≥ 80 years of age (n = 37), major complications (n = 11,29.7%) and non-home discharge (n = 9,24.3%) were quite common. 5-item modified frailty index ≥ 0.4 (OR 1.84,95%CI 1.06-3.19,p = 0.030), Male sex (OR 1.729,95%CI 1.152-2.595,p = 0.008), Age ≥ 65 (OR 1.63,95%CI 1.05-2.54,p = 0.29) and African-American race (OR 2.50,95%CI 1.22-5.16,p = 0.013) were independent predictors of major morbidity.

Conclusions: Pancreaticoduodenectomies in this setting have high rates of major complications. Morbidity extends beyond the index hospitalization, with frequent readmission and non-home discharge. Patient specific factors, rather than technical or disease factors predicted outcomes. In certain patients, particularly those older than 80, the morbidity of this operation may exceed the cancer prevention benefits.
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http://dx.doi.org/10.1016/j.hpb.2022.01.007DOI Listing
January 2022

Outcomes of pancreatectomy with portomesenteric venous resection and reconstruction for locally advanced pancreatic neuroendocrine neoplasms.

HPB (Oxford) 2021 Dec 31. Epub 2021 Dec 31.

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

Background: While pancreatectomy with portomesenteric venous resection and reconstruction is commonly performed for locally advanced pancreatic adenocarcinoma, little is known regarding outcomes for pancreatic neuroendocrine neoplasms (panNENs).

Methods: Patients who underwent non-parenchyma-sparing pancreatectomy for panNENs at Mayo Clinic from 2000 to 2020 were retrospectively reviewed. Propensity score matching was performed and patient characteristics and outcomes compared.

Results: Of 867 eligible patients, 41 (4.7%) required vascular resection, including 38 patients who underwent portomesenteric venous resection only. Of these, 23 underwent pancreaticoduodenectomy or total pancreatectomy and 15 distal pancreatectomy. Patients who required portomesenteric venous resection had larger tumors, higher tumor grade, and higher disease stage. After propensity score matching to patients undergoing standard resection, the portomesenteric venous resection group had longer operative times, greater blood loss, and higher transfusion rates. While portomesenteric venous thrombosis was more common after venous resection, major complication rates and perioperative mortality were similar between the two groups, as were 5-year overall and progression-free survival.

Conclusion: For patients with locally advanced panNENs, pancreatectomy with portomesenteric venous resection and reconstruction can be performed in selected patients at high-volume centers with acceptable perioperative morbidity and short- and long-term survival.
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http://dx.doi.org/10.1016/j.hpb.2021.12.016DOI Listing
December 2021

"Answers in hours": A prospective clinical study using nanopore sequencing for bile duct cultures.

Surgery 2022 03 29;171(3):693-702. Epub 2021 Dec 29.

Division of Surgical Research, Department of Surgery; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN. Electronic address:

Background: Surgical site infection is a major source of morbidity in patients undergoing pancreatic head resection and is often from organisms in intraoperative bile duct cultures. As such, many institutions use prolonged prophylactic antibiotics and tailor based on bile duct cultures. However, standard cultures take days, leaving many patients unnecessarily on prolonged antibiotics. Nanopore sequencing can provide data in hours and, thus, has the potential to improve antibiotic stewardship. The present study investigates the feasibility of nanopore sequencing in intraoperative bile samples.

Methods: Patients undergoing pancreatic head resection were included. Intra-operative bile microbial profiles were determined with standard cultures and nanopore sequencing. Antibiotic recommendations were generated, and time-to-results determined for both methods. Organism yields, resistance patterns, antibiotic recommendations, and costs were compared.

Results: Out of 42 patients, 22 (52%) had samples resulting in positive standard cultures. All positive standard cultures had microbes detected using nanopore sequencing. All 20 patients with negative standard cultures had negative nanopore sequencing. Nanopore sequencing detected more bacterial species compared to standard cultures (10.5 vs 4.4, p < 0.05) and more resistance genotypes (10.3 vs 2.7, p < 0.05). Antimicrobial recommendations based on nanopore sequencing provided coverage for standard cultures in 27 out of 44 (61%) samples, with broader coverage recommended by nanopore sequencing in 13 out of 27 (48%) of these samples. Nanopore sequencing results were faster (8 vs 98 hours) than standard cultures but had higher associated costs ($165 vs $38.49).

Conclusion: Rapid microbial profiling with nanopore sequencing is feasible with broader organism and resistance profiling compared to standard cultures. Nanopore sequencing has perfect negative predictive value and can potentially improve antibiotic stewardship; thus, a randomized control trial is under development.
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http://dx.doi.org/10.1016/j.surg.2021.09.037DOI Listing
March 2022

Synchronous colorectal liver metastases: therapeutic considerations.

Hepatobiliary Surg Nutr 2021 Oct;10(5):711-713

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

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http://dx.doi.org/10.21037/hbsn-21-239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527413PMC
October 2021

Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer.

Ann Surg Oncol 2022 Mar 1;29(3):1579-1591. Epub 2021 Nov 1.

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

Background: Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC.

Methods: We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded.

Results: Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p < 0.0001). On multivariable analysis, carbohydrate antigen (CA) 19-9 and pathologic treatment responses were predictors of RFS and OS.

Conclusion: CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.
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http://dx.doi.org/10.1245/s10434-021-10991-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810469PMC
March 2022

Surgical and reconstructive outcomes in primary venous leiomyosarcoma.

J Vasc Surg Venous Lymphat Disord 2022 Jul 2;10(4):901-907. Epub 2021 Aug 2.

Division of Vascular Surgery, Mayo Clinic Rochester, Rochester, Minn.

Objective: Primary venous leiomyosarcomas (PVL) are rare and pose challenges in surgical management. This study evaluates the clinical outcomes and identifies predictors of survival in our surgical series of PVL.

Methods: A retrospective review was performed of patients who had resection of PVL at three centers between 1990 and 2018. Patient demographics, comorbidities, intraoperative data, survival, and graft-related outcomes were recorded. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression.

Results: Seventy patients with a diagnosis of PVL were identified between 1990 and 2018. Fifty-four patients (77%) had PVL of the inferior vena cava (IVC) and 16 (23%) had peripheral PVL. The mean follow-up for the series was 55.0 months (range, 1-217 months). Fifty-one patients (96%) with IVC-PVL needed caval reconstruction and 3 (4%) had resection only. There were no deaths within 30 days of surgery. Five patients (9%) required early reintervention including one (2%) IVC stent. Sixteen peripheral PVL were identified. Eight patients (50%) had venous reconstructions performed and 8 (50%) had the vein resected without reconstruction. There were no deaths within 30 days. Five-year survival was 57.5% for IVC-PVL and 70.0% for peripheral PVL. Kaplan-Meier survival analysis for IVC and peripheral PVL revealed no difference in overall survival (P = .624) at 5 years.

Conclusions: PVL is a rare and aggressive disease even with surgical resection. We found no difference in survival between IVC and peripheral lesions, suggesting that aggressive management is warranted for PVL of any origin. Management of PVL requires a multidisciplinary approach to provide patients with the best long-term outcomes.
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http://dx.doi.org/10.1016/j.jvsv.2021.07.010DOI Listing
July 2022

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

J Surg Oncol 2021 Dec 26;124(7):1077-1084. 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
December 2021

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

Cancer Med 2021 09 21;10(17):5925-5935. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419760PMC
September 2021

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

Surgery 2021 12 3;170(6):1794-1798. Epub 2021 Jul 3.

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
December 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 07 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

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

HPB (Oxford) 2021 08 18;23(8):1277-1284. 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
August 2021

Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery.

Hepatology 2021 05 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 01 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

Current Indications and Long-Term Outcomes of Surgical Portosystemic Shunts in Adults.

J Gastrointest Surg 2021 06 18;25(6):1437-1444. Epub 2020 May 18.

Department of Vascular and Endovascular Surgery, Gonda Vascular Center, Hepatobiliary Pancreatic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Surgical portosystemic shunts are rare. We reviewed indications, operative details, and outcomes of patients undergoing surgical portosystemic shunt procedures.

Methods: We retrospectively reviewed clinical data of consecutive patients between 1997 and 2018 from a single institution. Clinical characteristics and outcomes were compared between two groups: patients with portomesenteric venous thrombosis (PMVT) vs those with cirrhosis. Endpoints included 30-day mortality, shunt-related complications, patency, and survival.

Results: There were 99 patients, 45 male and 54 female, with a mean age of 46 ± 18 years, enrolled in the study. There were 63 patients (63%) with PMVT and 36 patients (36%) with cirrhosis. Both groups had similar demographics, cardiovascular risk factors, and aneurysm extent, except for more diabetes among those with cirrhosis (p < 0.05). There were no significant differences in procedural metrics and intra-procedure complications between groups, except that patients with PMVT underwent more non-selective shunts than those with cirrhosis (63% vs. 30%, p < 0.001). There were two 30-day deaths (2%), with no difference in mortality and MAEs between groups. On univariate analysis, cholangiopathy and PMVT were associated with graft thrombosis (HR = 9.22, 95% CI 1.22-70.27) while race, smoking, cardiac comorbidity, type of operative shunt, configuration of the shunt, and use of conduit were not (p > 0.05). Patients with PMVT had significantly lower 1-, 5-, and 10-year primary (77%, 71%, and 71% vs. 97%, p = 0.009) and secondary patency (88%, 76%, and 72% vs. 96%, p = 0.027) compared with those with cirrhosis. The 1-, 5-, and 10-year survival rates were 94%, 84%, and 61% for patients with PMVT compared with 88%, 58%, and 26% for those with cirrhosis (non-adjusted HR 0.40, 95% CI 0.19-0.84, p = 0.01, age-adjusted HR 0.51, 95% CI 0.24-1.09, p = 0.08). The survival of patients with PMVT without liver disease trended higher than those with liver disease; however, when adjusted for age, the survival gap narrowed, and the difference was not statistically significant (p = 0.19), survival being lowest for those with PMVT and liver disease.

Conclusions: Surgical portosystemic shunts are safe and effective for symptom relief in selected patients with portal hypertension. The odds of graft thrombosis is 9 times higher in patients with PMVT. Overall survival is similar in patients with PMVT or cirrhosis.
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http://dx.doi.org/10.1007/s11605-020-04643-1DOI Listing
June 2021

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

Symptom relief and quality of life after combined partial hepatectomy and cyst fenestration in highly symptomatic polycystic liver disease.

Surgery 2020 07 8;168(1):25-32. Epub 2020 May 8.

Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN; Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN. Electronic address:

Background: Polycystic liver disease can cause severe symptomatic hepatomegaly. Combined partial hepatectomy and cyst fenestration can be performed to reduce liver volume and symptom burden. We aimed to assess change in symptom relief and quality of life 6 months after partial hepatectomy and cyst fenestration in polycystic liver disease patients.

Method: We established a prospective cohort between 2014 and 2018 at a referral center in the United States. Patients who underwent partial hepatectomy and cyst fenestration for volume-related symptoms were included. Primary outcome was change in polycystic liver disease-related symptoms, measured with Polycystic Liver Disease Questionnaire. Secondary outcomes were change in liver volume (computed tomography/ magnetic resonance imaging) and change in quality of life, measured with the 12-Item Short Form Survey and the EuroQoL Visual Analogue Scale. Questionnaire scores range from 0 to 100 and were assessed before and 6 months after partial hepatectomy and cyst fenestration. Surgical complications were scored according to Clavien-Dindo (grade 1 to 5).

Results: We included 18 patients (mean age 52 years, 82% female). Partial hepatectomy and cyst fenestration reduced median liver volume (4,917 to 2,120 mL). Symptoms, measured with Polycystic Liver Disease Questionnaire, decreased (76.9 to 34.8 points; P < .001) 6 months after surgery; 15/16 symptoms declined after treatment, with the most impact seen on early satiety and dyspnea. Quality of life also improved after surgery: median physical and mental component scales of the 12-Item Short Form Survey and EuroQoL Visual Analog Scale increased (24.9 to 45.7, P = .004; 40.5 to 55.4, P = .02; and 40.0 to 72.5, P = .003). Major complications (grade 4) occurred in 2 patients. There was no procedure-related mortality.

Conclusion: Partial hepatectomy and cyst fenestration substantially improves symptom burden and quality of life in highly symptomatic polycystic liver disease patients.
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http://dx.doi.org/10.1016/j.surg.2020.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347464PMC
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

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

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

Is There a Role for Liver Transplantation in the Treatment of Patients With Metastatic Colorectal Cancer?

Ann Surg 2020 02;271(2):219-220

Division of Medical Oncology, Mayo Clinic Rochester and Mayo College of Medicine, Rochester, MN.

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http://dx.doi.org/10.1097/SLA.0000000000003713DOI Listing
February 2020

Survival benefit of neoadjuvant therapy in patients with non-metastatic pancreatic ductal adenocarcinoma: A propensity matching and intention-to-treat analysis.

J Surg Oncol 2019 Nov 26;120(6):976-984. Epub 2019 Aug 26.

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

Background And Objectives: Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC.

Methods: The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis.

Results: In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001).

Conclusions: The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC.
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http://dx.doi.org/10.1002/jso.25681DOI Listing
November 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

Bacterial Cholangitis in Autosomal Dominant Polycystic Kidney and Liver Disease.

Mayo Clin Proc Innov Qual Outcomes 2019 Jun 27;3(2):149-159. Epub 2019 May 27.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.

Objective: To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD).

Patients And Methods: We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD.

Results: We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio [OR], 21.6; 95% CI, 3.17-927; <.001), prior cholecystectomy (OR, 12.2; 95% CI, 1.59-552; =.008), duodenal diverticulum (OR, 13.5; 95% CI, 2.44 to not estimable; =.004), type 2 diabetes mellitus (OR, 6.41; 95% CI, 1.01 to not estimable; =.05), prior endoscopic retrograde cholangiopancreatography (OR, 14.0; 95% CI, 1.80-631; =.005), and prior kidney transplant (OR, 8.06; 95% CI, 1.72-76.0; =.004) were higher in patients with ADPKD-associated PLD with definite cholangitis compared to controls.

Conclusion: Gallstones, prior cholecystectomy, duodenal diverticulosis, type 2 diabetes mellitus, prior endoscopic retrograde cholangiopancreatography, and prior kidney transplant constituted risk factors for cholangitis among patients with ADPKD-associated PLD.
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http://dx.doi.org/10.1016/j.mayocpiqo.2019.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543502PMC
June 2019

Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma.

Clin Colorectal Cancer 2019 09 15;18(3):218-225. Epub 2019 May 15.

Division of Medical Oncology, Mayo Clinic, Rochester, MN. Electronic address:

Background: Small bowel adenocarcinoma (SBA) is a rare malignancy affecting approximately 3000 patients per year in the United States, and there is limited evidence prognosticating patients with resected SBA. We aimed to evaluate prognostic factors and the role of adjuvant therapy in patients with resected SBA.

Patients And Methods: Two hundred forty-one patients who had resected stage I-III SBA were retrospectively identified at a single tertiary referral institution. Overall survival (OS) analysis was performed by the Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed to identify significant variables by univariate and multivariate analysis.

Results: Median OS for the entire group was 54.5 months (95% confidence interval [CI], 37.2-81.2 months), with 5- and 10-year OS of 48% and 35%. Median follow-up was 113.7 months (95% CI, 97.9-126.6 months). For patients with stage III disease who received adjuvant therapy, the median OS was 33.8 months (95% CI, 27.8-78.8) compared to 24.7 months (95% CI, 11.5-37.8) for patients with no adjuvant therapy (P < .01). Male sex, advanced T stage, advanced N stage, increased positive lymph node ratio, lymphocyte-to-monocyte ratio < 1.56, presence of residual disease, and earlier date of diagnosis predicted worse survival on univariate analysis. Age > 60 years, lymphocyte-to-monocyte ratio < 1.56, and advanced T stage were identified as independent negative predictors of OS for all patients by multivariate analysis.

Conclusion: Advanced age, advanced T stage, and lymphocyte-to-monocyte ratio < 1.56 independently predicted survival in resected SBA. Adjuvant therapy is associated with improved survival in patients with resected stage III SBA.
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http://dx.doi.org/10.1016/j.clcc.2019.05.002DOI 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
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