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1.
HPB (Oxford) ; 22(3): 398-404, 2020 03.
Article En | MEDLINE | ID: mdl-31416785

BACKGROUND: A triple-row stapler is widely used to divide the pancreas in distal pancreatectomy (DP). However, the selection criteria of the stapler cartridge to prevent postoperative pancreatic fistula (POPF) remain unclear. The objective of this study was to determine if factors concerning pancreatic thickness or staple size affect POPF after DP. METHODS: Datasets of patients from the Mayo Clinic and National Cancer Center Hospital East who underwent DP using a triple-row stapler were merged. Risk of POPF was analyzed using clinicopathological variables, including data for pancreatic thickness and staple height. A compression index was defined as the designated staple height (mm) after closure divided by the pancreatic thickness (mm). RESULTS: Among the 277 patients, POPF occurred in 65 (23%) patients. The median pancreatic thickness was 13.7 mm and the median compression index was 0.137. Multivariable logistic models showed that a greater pancreatic thickness (odds ratio, 1.190, P < 0.001) and a compression index ≤0.160 (odds ratio, 4.754, P < 0.001) were independently related with POPF. CONCLUSION: In patients undergoing DP using a triple-row stapler, the thickness of the pancreas was related with the occurrence of POPF. Selection of the stapler cartridge with a compression index of ≤0.160 may reduce the occurrence of POPF.


Pancreas/pathology , Pancreatectomy/adverse effects , Pancreatic Fistula/epidemiology , Postoperative Complications/epidemiology , Surgical Staplers/adverse effects , Surgical Stapling/adverse effects , Adult , Aged , Aged, 80 and over , Equipment Design/adverse effects , Female , Humans , Male , Middle Aged , Pancreatectomy/instrumentation , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Retrospective Studies , Risk Factors , Surgical Stapling/instrumentation , Treatment Outcome , Young Adult
2.
J Surg Oncol ; 120(6): 976-984, 2019 Nov.
Article En | MEDLINE | ID: mdl-31452208

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.


Adenocarcinoma/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/mortality , Intention to Treat Analysis , Neoadjuvant Therapy/mortality , Pancreatectomy/mortality , Pancreatic Neoplasms/mortality , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Chemotherapy, Adjuvant , Cohort Studies , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Propensity Score , Survival Rate , Young Adult , Pancreatic Neoplasms
3.
J Am Coll Surg ; 227(2): 255-269, 2018 08.
Article En | MEDLINE | ID: mdl-29752997

BACKGROUND: Pancreatectomy with arterial resection (AR) is performed infrequently. As indications evolve, we evaluated indications, outcomes, and predictors of mortality, morbidity, and survival after AR. STUDY DESIGN: We performed a single-institution review of elective pancreatectomies with AR (from July1990 to July 2017). Univariate and multivariate analyses were performed for predictors of outcomes and survival. RESULTS: A total of 111 patients underwent pancreatectomy with AR including any hepatic (54%), any celiac (44%), any superior mesenteric (14%), or multiple ARs (14%), with revascularization in 55%. The majority of cases were planned (77%) and performed post-2010 (78%). Overall 90-day major morbidity (≥grade III) and mortality were 54% and 13%, respectively, due to post-pancreatectomy hemorrhage (PPH), postoperative pancreatic fistula (POPF), or ischemia in the majority of cases. There was a significant decrease in mortality post-2010 (9% vs 29%, p = 0.02), and this was protective on multivariate analysis (odds ratio [OR] 0.1, p = 0.004); PPH increased mortality (OR 6.1, p < 0.001). Post-pancreatectomy hemorrhage was associated with major morbidity (OR 5.1, p = 0.005), reoperation (OR = 23.0, p = 0.004), ICU (OR 5.5, p < 0.001), and readmission (OR 2.6, p = 0.004). Other morbidity predictors were AR with graft (OR 4.0, p = 0.031) and POPF (OR 3.1, p = 0.003). Median survival was 28.5 months and improved for ductal adenocarcinoma after neoadjuvant chemotherapy (p = 0.038). There were no differences in survival based on AR type. CONCLUSIONS: Regardless of indication or type, pancreatectomy with AR is associated with risks greater than standard resections. Mortality has decreased in the modern era; however, morbidity remains high from hemorrhagic, fistula, or ischemia-related complications. Mitigation measures are needed if advanced resections are considered with increasing frequency given the potential oncologic benefit of AR in selected cases after modern chemotherapy.


Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Patient Selection , Vascular Surgical Procedures/methods , Female , Humans , Male , Middle Aged , Pancreatectomy/mortality , Postoperative Complications/mortality , Retrospective Studies , Survival Rate , Treatment Outcome , Vascular Surgical Procedures/mortality
4.
J Gastrointest Surg ; 22(5): 831-839, 2018 05.
Article En | MEDLINE | ID: mdl-29392613

BACKGROUND: The aim of this study was to investigate the impact of decreased skeletal muscle (SM) volume on survival outcomes in patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Between March 2000 and February 2015, 323 patients who underwent upfront surgical resection for PDAC were identified from the Mayo Clinic SPORE in Pancreatic Cancer. Body composition data, including SM area, subcutaneous adipose tissue area, and visceral adipose tissue area were calculated using an abdominal computed tomography (CT) image at the third lumbar spinal level. The body composition data were normalized by patients' height (e.g., SM index, cm2/m2) and analyzed as continuous variables. Clinicopathological findings and body composition data at initial diagnosis were evaluated for association with overall survival and recurrence-free survival. RESULTS: Because the median SM index was significantly different between males vs. females (49.9 cm2/m2 [range, 32.0-70.3] vs. 39.4 cm2/m2 [range, 29.2-66.2], P < 0.001), it was standardized for each sex and used for further analyses. Parameters independently associated with a shorter overall survival were a larger tumor size (P = 0.007), a greater tumor extent (P = 0.037), a higher carbohydrate antigen 19-9 level (P < 0.001), and a smaller sex-standardized SM index (P = 0.011). Parameters independently associated with a shorter recurrence-free survival were female sex (P = 0.029), a larger tumor size (P < 0.001), a higher carbohydrate antigen 19-9 level (P = 0.001), and a smaller sex-standardized SM index (P = 0.007). CONCLUSIONS: A smaller sex-standardized SM index is a predictive factor for shorter overall and recurrence-free survival in PDAC patients undergoing surgery.


Body Composition , Carcinoma, Pancreatic Ductal/surgery , Muscle, Skeletal , Pancreatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , CA-19-9 Antigen/blood , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/pathology , Disease-Free Survival , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Sex Factors , Subcutaneous Fat/diagnostic imaging , Survival Rate , Tomography, X-Ray Computed , Tumor Burden
5.
Surgery ; 163(3): 495-502, 2018 03.
Article En | MEDLINE | ID: mdl-29275974

BACKGROUND: Morbidity and costs after pancreatoduodenectomy remain increased, driven by postoperative pancreatic fistula (POPF). A risk-based pathway for pancreatoduodenectomy (RBP-PD) was implemented and the clinical and cost outcomes compared with that of our historic practice. METHODS: Prospective clinical and cost outcomes for our RBP-PD cohort treated from September 2014 to September 2015 were compared with a previously published cohort of pancreatoduodenectomies from January 2007 to February 2014. RESULTS: A total of 128 RBP-PD cases were compared with 808 historic controls. Apart from less blood loss, there were no significant clinical differences between the 2 groups. Overall POPF rate did not change. Average duration of stay decreased to 10 days from 12 (P < .001) despite similar readmission rates. Postsurgical interventional radiology procedures decreased to 18.0% from 26.4% (P = .048). Utilization of and duration of stay in monitored care decreased to 23.4% from 35.6% (P < .01) and to 1 day from 3 (P < .01). On multivariable analysis RBP-PD was independently associated with decreased odds of higher postoperative pancreatic fistula grade, monitored care, and prolonged duration of stay. Inpatient cost of care decreased $6,387 per patient (-11.1%, P = .016), and total 30-day costs decreased $8,565 per patient (-13.7%, P = .01), representing a total 30-day cost savings of $1.1 million. CONCLUSION: RBP-PD significantly improved patient outcomes, decreased costs of care, and likely has applicability for surgical care beyond pancreatoduodenectomy.


Cost Savings , Critical Pathways , Health Care Costs , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy/economics , Postoperative Complications/prevention & control , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Pancreatic Fistula/economics , Pancreatic Fistula/epidemiology , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/economics , Postoperative Complications/epidemiology , Risk Assessment , Treatment Outcome
6.
Ann Surg Oncol ; 24(6): 1731-1738, 2017 Jun.
Article En | MEDLINE | ID: mdl-28070725

INTRODUCTION: Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). METHODS: The National Cancer Data Base (2004-2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. RESULTS: Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90-1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). CONCLUSION: Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.


Adenocarcinoma/surgery , Chemotherapy, Adjuvant/mortality , Databases, Factual , Pancreatectomy/mortality , Pancreatic Neoplasms/surgery , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Invasiveness , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate
7.
Clin Gastroenterol Hepatol ; 15(2): 299-302.e4, 2017 02.
Article En | MEDLINE | ID: mdl-27539084

Synchronous primary pancreatic adenocarcinoma, defined as the simultaneous presence of 2 or more newly identified and anatomically separate primary adenocarcinomas within the pancreas, is reported rarely. We compared endoscopic ultrasound (EUS) and computed tomography (CT) and magnetic resonance imaging (MRI) findings from patients with synchronous primary pancreatic adenocarcinoma and their effects on cancer staging and treatment. We performed a retrospective analysis of the EUS database at the Mayo Clinic, from September 2008 through May 2016, to collect EUS, CT, MRI, and clinical data from patients with synchronous primary pancreatic adenocarcinoma. EUS and separate fine-needle aspiration of both tumors detected synchronous primary pancreatic adenocarcinoma in 11 patients (70.9 ± 10.4 y; 64% men). Of the 22 cancers, CT (n = 9) and MRI (n = 2) detected 9 (41%) cancers; in only 2 patients did CT detect both cancers. EUS increased cancer stage for 7 of the 11 (64%) patients and changed the status from resectable to unresectable for 3 of the 9 (33%) patients, compared with CT or MRI. EUS findings altered the likely extent of surgical resection for 3 patients. Synchronous primary pancreatic adenocarcinoma is reported rarely and may be undetected by CT or MRI; this could account for the false presumption of early tumor recurrence, rather than actual residual second tumor, leading to incomplete resection.


Adenocarcinoma/diagnosis , Biopsy, Fine-Needle/methods , Endosonography/methods , Pancreatic Neoplasms/diagnosis , Adenocarcinoma/diagnostic imaging , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasm Staging/methods , Pancreatic Neoplasms/diagnostic imaging , Prospective Studies , Retrospective Studies , Tomography, X-Ray Computed/methods
8.
Gastrointest Endosc ; 86(1): 150-155, 2017 Jul.
Article En | MEDLINE | ID: mdl-27773725

BACKGROUND AND AIMS: Malignant vascular invasion usually results from gross direct infiltration from a primary tumor and impacts cancer staging, prognosis, and therapy. However, patients may also develop a remote malignant thrombi (RMT), defined as a malignant intravascular thrombus located remote and noncontiguous to the primary tumor. Our aim was to compare EUS, CT, and magnetic resonance imaging (MRI) findings of RMT and to explore the potential impact on cancer staging. METHODS: Patients with RMT were identified from a prospectively maintained EUS database. Retrospective chart review was performed to obtain EUS, CT/MRI, clinical, and outcome data. RESULTS: A median of 3 FNAs (range, 1-8) was obtained from RMT in 17 patients (60 ± 14.1 years, 56% men) between April 2003 and August 2016, with the finding of malignant cytology in 12 patients (70.6%; 10 positive, 2 suspicious). CT/MRI detected the RMT in 5 patients (29.4%), 4 of whom had positive or suspicious EUS-FNA cytology. Among the 8 newly diagnosed pancreatic adenocarcinoma (PaC) patients, CT did not detect the RMT in 5 (63%), of whom 3 patients had positive or suspicious intravascular EUS-FNA cytology. For newly diagnosed PaC patients (n = 8), the EUS-FNA diagnosis of a biopsy specimen-proven RMT upstaged 3 patients (37.5%) and converted 2 patients (25%) from CT resectable to unresectable disease. No adverse events were reported. The mean follow-up was 18.9 ± 27.7 months. CONCLUSIONS: Our study demonstrates the ability and potential safety of intravascular FNA to detect radiographically occult RMT, which substantially impacts cancer staging and resectability.


Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Neoplastic Cells, Circulating/pathology , Pancreatic Neoplasms/pathology , Vascular Neoplasms/diagnostic imaging , Vascular Neoplasms/pathology , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Endosonography , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Tomography, X-Ray Computed , Vascular Neoplasms/secondary
9.
Gastrointest Endosc ; 86(1): 161-169, 2017 Jul.
Article En | MEDLINE | ID: mdl-27889543

BACKGROUND AND AIMS: Among the greatest hurdles to pancreatic cancer (PC) therapy is the limited tissue penetration of systemic chemotherapy because of tumor desmoplasia. The primary study aim was to determine the toxicity profile of EUS-guided fine-needle injection (EUS-FNI) with gemcitabine. Secondary endpoints included the ability to disease downstage leading to an R0 resection and overall survival (OS) at 6 months, 12 months, and 5 years after therapy. METHODS: In a prospective study from a tertiary referral center, gemcitabine (38 mg/mL) EUS-FNI was performed in patients with PC before conventional therapy. Initial and delayed adverse events (AEs) were assessed within 72 hours and 4 to 14 days after EUS-FNI, respectively. Patients were followed for ≥5 years or until death. RESULTS: Thirty-six patients with stage II (n = 3), stage III (n = 20), or stage IV (n = 13) disease underwent gemcitabine EUS-FNI with 2.5 mL (.7-7.0 mg) total volume of injectate per patient. There were no initial or delayed AEs reported. Thirty-five patients (97.2%) were deceased at the time of analysis with a median 10.3 months of follow-up (range, 3.1-63.9). OS at 6 months and 12 months was 78% and 44%, respectively. The median OS was 10.4 months (range, 2.7-68). Among patients with stage III unresectable disease, 4 (20%) were downstaged and underwent an R0 resection. CONCLUSIONS: Our study suggests the feasibility, safety, and potential efficacy of gemcitabine EUS-FNI for PC. Additional data are needed to verify these observations and to determine the potential role relative to conventional multimodality therapy.


Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Endosonography , Female , Follow-Up Studies , Humans , Injections, Intralesional , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Response Evaluation Criteria in Solid Tumors , Survival Rate , Ultrasonography, Interventional , Gemcitabine
10.
J Surg Res ; 206(1): 32-40, 2016 11.
Article En | MEDLINE | ID: mdl-27916372

BACKGROUND: Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD. METHODS: A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD. RESULTS: Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm (P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD (P = 0.35). There were no statistically significant differences in major or any pancreatic fistula-related morbidity between the two groups. CONCLUSIONS: This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics.


Pancreatectomy/methods , Pancreatic Diseases/prevention & control , Postoperative Complications/prevention & control , Wound Closure Techniques , Adolescent , Adult , Aged , Aged, 80 and over , Catheter Ablation , Early Termination of Clinical Trials , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pancreatectomy/instrumentation , Pancreatic Diseases/epidemiology , Pancreatic Diseases/etiology , Postoperative Complications/epidemiology , Prospective Studies , Surgical Mesh , Surgical Stapling , Treatment Outcome , Wound Closure Techniques/instrumentation , Young Adult
11.
HPB (Oxford) ; 18(11): 886-892, 2016 11.
Article En | MEDLINE | ID: mdl-27546172

BACKGROUND: Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB). METHODS: Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival. RESULTS: The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p < 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p < 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p < 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions. DISCUSSION: cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate.


Bile Duct Neoplasms/pathology , Carcinoma, Hepatocellular/pathology , Cholangiocarcinoma/pathology , Liver Neoplasms/pathology , Neoplasms, Complex and Mixed/pathology , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Chi-Square Distribution , Cholangiocarcinoma/mortality , Cholangiocarcinoma/surgery , Databases, Factual , Female , Hepatectomy , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Neoplasms, Complex and Mixed/mortality , Neoplasms, Complex and Mixed/surgery , Phenotype , Proportional Hazards Models , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
12.
Surgery ; 160(4): 1080-1096, 2016 10.
Article En | MEDLINE | ID: mdl-27522556

BACKGROUND: Outcomes of neoadjuvant systemic therapy versus an upfront operation for clinical, stage III pancreatic adenocarcinoma remain poorly defined. Our aim was to compare survival among patients receiving neoadjuvant chemotherapy versus surgery-first with an intention-to-treat analysis. METHODS: The National Cancer Data Base was reviewed from 2002-2011 for patients with clinical, stage III adenocarcinoma of the head or body of the pancreas. Patients were categorized as neoadjuvant or surgery-first. The intention-to-treat analysis included all neoadjuvant therapy patients in whom a potentially curative operation was planned and all surgery-first patients for whom adjuvant therapy was recommended. Intention-to-treat overall survival was compared by Kaplan-Meier and Cox proportional hazards multivariable regression. RESULTS: A total of 593 patients were identified: 377 (63.6%) in the neoadjuvant cohort, wherein 104 (27.6%) experienced preoperative attrition, and 216 (36.4%) in the surgery-first cohort, of whom 30 (13.9%) failed to receive intended adjuvant chemotherapy. Intention-to-treat Kaplan-Meier analysis demonstrated superior survival for neoadjuvant compared to surgery-first (median overall survival 20.7 months vs 13.7 months, log rank P < .001). Intention-to-treat multivariable regression analysis revealed a decreased mortality hazard (hazard ratio = 0.68, 95% confidence interval 0.53-0.86, P = .0012) for neoadjuvant compared to surgery-first. CONCLUSION: Despite preoperative attrition, neoadjuvant therapy in clinical, stage III pancreatic cancer patients is associated with improved overall survival when compared to patients receiving surgery-first.


Adenocarcinoma/mortality , Adenocarcinoma/therapy , Neoadjuvant Therapy/methods , Pancreatectomy/methods , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Chemotherapy, Adjuvant , Cohort Studies , Databases, Factual , Disease-Free Survival , Female , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Pancreatectomy/mortality , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome , United States
13.
J Surg Oncol ; 114(4): 475-82, 2016 Sep.
Article En | MEDLINE | ID: mdl-27439662

BACKGROUND: Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination. METHODS: The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed. RESULTS: A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased long-term survival. In adjusted analysis, CA19-9 elevation independently predicted increased mortality with impact similar to node-positivity, positive-margin resection, and non-receipt of chemotherapy. Proposed staging system including CA19-9 improved survival discrimination over AJCC 7th edition. CONCLUSION: Elevated CA19-9 is an independent risk factor for mortality in ICCA similar in impact to nodal metastases and positive resection margins. Inclusion of CA19-9 in a proposed staging system increases discrimination. Multi-disciplinary therapy should be considered in patients with ICCA and CA19-9 elevation. J. Surg. Oncol. 2016;114:475-482. © 2016 Wiley Periodicals, Inc.


Bile Duct Neoplasms/therapy , CA-19-9 Antigen/blood , Cholangiocarcinoma/therapy , Aged , Bile Duct Neoplasms/blood , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/blood , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Neoplasm Staging , Proportional Hazards Models
14.
J Am Coll Surg ; 223(1): 52-65, 2016 07.
Article En | MEDLINE | ID: mdl-27049786

BACKGROUND: Patient triage in anatomically resectable, early stage pancreatic ductal adenocarcinoma (PDAC) with elevated carbohydrate antigen 19-9 (CA 19-9) remains unclear. We hypothesized that any CA 19-9 elevation indicates biologically borderline resectability. STUDY DESIGN: The National Cancer Data Base (NCDB 2010 to 2012) was reviewed for PDAC patients with reported CA 19-9. Nonsecretors were analyzed separately. Early stage (I/II) patients were stratified by CA 19-9 above or below normal (37 U/mL). Unadjusted Kaplan-Meier and adjusted Cox proportional hazards survival modeling were performed. RESULTS: Of 113,145 patients, only 28,074 (24.8%) had CA 19-9 measured and reported, and this proportion was stage independent. Among early stage patients (n = 10,806), there were 957 (8.8%) nonsecretors, 2,708 (25.1%) with normal levels, and 7,141 (66.1%) with elevated levels. Demographics and perioperative outcomes were similar between these groups. Survival was worse in all stages in patients with CA 19-9 elevation. Nonsecretors had survival similar to that of patients with normal levels. Early stage patients with elevated CA 19-9 had decreased survival at 1, 2, and 3 years (56% vs 68%, 30% vs 42%, 15% vs 25%, all p < 0.001) relative to patients with normal levels. Adjusted modeling confirmed this finding (hazard ratio [HR] 1.26, p < 0.001). Repeat modeling in the neoadjuvant cohort demonstrated this to be the only treatment sequence to completely abrogate increased mortality due to CA 19-9 elevation (p = 0.11). CONCLUSIONS: The minority of PDAC patients have CA 19-9 measured and reported in NCDB. The CA 19-9 nonsecretors and normal-level patients achieve equivalent survival. Elevation of CA 19-9 is associated with decreased stage-specific survival, with the greatest difference in early stages. Neoadjuvant systemic therapy followed by curative intent surgery best mitigates the increased mortality hazard. Patients with PDAC who have elevated CA 19-9 levels at diagnosis are biologically borderline resectable regardless of anatomic resectability, and neoadjuvant systemic therapy is suggested.


CA-19-9 Antigen/blood , Carcinoma, Pancreatic Ductal/therapy , Pancreatectomy , Pancreatic Neoplasms/therapy , Pancreaticoduodenectomy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Chemotherapy, Adjuvant , Databases, Factual , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Radiotherapy, Adjuvant , Retrospective Studies , Survival Analysis , Treatment Outcome
16.
Pancreatology ; 16(3): 391-6, 2016.
Article En | MEDLINE | ID: mdl-27107633

OBJECTIVE: Autoimmune pancreatitis (AIP) responds dramatically to corticosteroids treatment. We reviewed our experience to determine the safety and effectiveness of treating obstructive jaundice in definitive AIP with corticosteroids alone without biliary stenting. METHODS: From our AIP database, we retrospectively identified type 1 AIP subjects whose jaundice was treated with corticosteroids alone without biliary stenting. Their medical records were reviewed and clinical data were evaluated to determine the outcomes. RESULTS: Fifteen AIP subjects (87% male, mean age 68.4 years) were treated with corticosteroids at initial presentation (n = 8), first (n = 5) or subsequent (n = 2) relapse. Mean values (upper limit of normal, ULN) of liver tests prior to corticosteroids were aspartate aminotransferase (AST) 203.5u/l (4 × ULN), alanine aminotransferase (ALT) 325.8u/l (6 × ULN), alkaline phosphatase (ALP) 567.4u/l (5 × ULN), and total bilirubin (TB) 5.9 mg/dl (5.9 × ULN). At first follow-up (mean 4 days) the decrease was 54.9% for AST, 51.6% for ALT, 33% for ALP and 47.2% for TB (all p < 0.05). After 15-45 days, all patients had normal AST, 3/15 had ALT > 1.5 × ULN, 1/15 had ALP > 1.5 × ULN, 1/15 had TB > 1.5 × ULN. No patient required biliary stent placement, or developed cholangitis or other infectious complications during steroid treatment. CONCLUSION: Under the supervision of an experienced pancreatologist and with close monitoring of patients, obstructive jaundice secondary to definitive AIP can be safely and effectively managed with corticosteroids alone, without the need for biliary stenting.


Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Autoimmune Diseases/complications , Jaundice, Obstructive/drug therapy , Pancreatitis, Chronic/complications , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Jaundice, Obstructive/etiology , Male , Middle Aged , Retrospective Studies , Stents , Treatment Outcome
17.
J Gastrointest Surg ; 20(5): 891-8, 2016 05.
Article En | MEDLINE | ID: mdl-26925796

Efficacy and outcomes of resection for pancreatic neuroendocrine tumors (pNET) are well established; specific data on outcomes for pancreaticoduodenectomy (PD), either alone or with combined procedures, are limited. A retrospective review of PDs for pNET (1998-2014) at our institution was conducted. Patients were categorized into standard PD (SPD) alone or combined PD (CPD) defined as patients undergoing concurrent vascular reconstruction or additional organ resection for curative intent. Kaplan-Meier survival analyses were performed. PD for pNET was performed for 95 patients. Tumors were functional in 11 patients (9 %). Twenty-six patients (28 %) underwent CPD. The 30/90-day mortality was 1.1/5.3 % respectively and similar between SPD and CPD (p = 0.61/p = 0.24). Five-year overall survival after PD for pNET was 85.1/71.9 % and similar between SPD/CPD groups (p = 0.17). Recurrence-free and overall survival for low-grade tumors was 74.7/93.9 % at 5 years compared to only 14.8/49.7 % for high-grade tumors (p < 0.001) and not predicted by extent of resection (SPD/CPD, respectively). PD with or without concurrent resection provides an acceptable, perioperative and long-term oncologic, outcome for pNET. CPD is justified treatment modality, particularly for patients with low-grade tumors. The need for combinatorial procedures during PD is not contraindication alone for otherwise resectable patients with pNET.


Carcinoma, Neuroendocrine/surgery , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
18.
J Gastrointest Surg ; 20(1): 189-98; discussion 198, 2016 Jan.
Article En | MEDLINE | ID: mdl-26553267

PURPOSE: In patients undergoing elective partial pancreatectomy, our aim was to evaluate the effect of metabolic syndrome (MS) on postoperative mortality, morbidity, and utilization of hospital resources. Our hypothesis was that MS is associated with worse surgical outcomes after pancreatectomy. METHODS: Fifteen thousand eight hundred thirty-one patients undergoing elective pancreatectomy from 2005 to 2012 were identified in the Participant User File of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Univariable and multivariable analyses were performed examining the association of MS (defined as body mass index ≥30 kg/m(2), hypertension requiring medications, and diabetes requiring medications and/or insulin) and risk of 30-day mortality, morbidity, and utilization of hospital resources (risk of blood transfusion in the first 72 h after pancreatectomy and prolonged hospital stay, defined as ≥13 days, which was the 75th percentile of this cohort). Multivariable logistic regression models controlled for age, sex, race, pancreatectomy type (distal versus proximal), smoking status, alcohol consumption, functional status, dyspnea, cardiovascular disease, hematocrit, INR, serum albumin, bilirubin, and creatinine. Stratified analyses were conducted by type of pancreatectomy and indication for pancreatectomy (benign versus malignant). RESULTS: On univariate analysis, 1070 (6.8%) patients had MS. MS was associated with increased postoperative morbidity, major morbidity, surgical site infection, septic shock, cardiac event, respiratory failure, pulmonary embolism, blood transfusion, and prolonged duration of hospital stay (P < 0.05 for all analyses). After controlling for potentially confounding variables, there was a 26% increased odds of postoperative morbidity (P < 0.001), 17% increased odds of major morbidity (P = 0.034), 32% increased odds of surgical site infection (P < 0.001), 34% increased odds of respiratory failure (P = 0.023), 68% increased odds of pulmonary embolism (P = 0.045), 26% increased odds of blood transfusion (P = 0.018), and 21% increased odds of prolonged hospital stay (P = 0.011) in patients with MS compared to patients without MS. MS was not associated with 30-day mortality after elective pancreatectomy (P = 0.465). When stratified by distal versus proximal pancreatectomy and benign versus malignant disease, the effect of MS on outcomes appears to be modified by type of pancreatectomy and indication with poorer outcomes observed for distal pancreatectomies and benign indications for resection. CONCLUSION: MS is an under-emphasized predictor of increased postoperative morbidity and utilization of hospital resources in patients undergoing elective pancreatectomy. The effect of MS on these postoperative outcomes appears to be more pronounced for patients with benign rather than malignant indications for pancreatectomy and in patients undergoing distal rather than proximal pancreatectomy. These results may inform patient selection, optimization of comorbidities prior to elective pancreatectomy, and strategies for postoperative management.


Metabolic Syndrome/complications , Pancreatectomy , Postoperative Complications , Aged , Blood Transfusion , Elective Surgical Procedures , Female , Humans , Length of Stay , Logistic Models , Male , Middle Aged , Pancreatectomy/mortality , Patient Selection , Postoperative Care , Risk Factors
19.
J Gastrointest Surg ; 19(12): 2146-53, 2015 Dec.
Article En | MEDLINE | ID: mdl-26334250

BACKGROUND: Over the last 30 years, numerous developments in the management of chronic pancreatitis have occurred, leading to multiple surgical and non-surgical options. PATIENTS AND METHODS: All patients who underwent pancreatoduodenectomy for chronic pancreatitis from January 1976 to July 2013 were reviewed. Surviving patients were contacted for a follow-up questionnaire and Short Form (SF)-12 Quality of Life Survey administration. RESULTS: A total of 166 patients were identified (cohort 1:1976-1997(N = 105) and cohort 2:1998-2013(N = 61)). Prior to pancreatoduodenectomy, a higher proportion of patients in cohort 2 had undergone endoscopic stenting, 67 vs 10 % (p < 0.001) and/or celiac plexus block 15 and 5 % (p = 0.026). Median follow-up for all survey respondents was 15 years. On the SF-12, mean physical component score was 43.8 ± 11.8 and mental component score was 54.3 ± 7.9. Patients were significantly lower on the physical component score (p < 0.001) and significantly better on the mental component score (p = 0.001) than the general US population. Mean pain score out of 10 was significantly lower after surgery 1.6 ± 2.6 than before surgery 7.9 ± 3.5 (p < 0.001). Diabetes developed in 28 % of patients who were not diabetic prior to surgery. CONCLUSION: Although practice has changed so that patients have a longer time from presentation until surgery as less-invasive techniques are attempted, pancreatoduodenectomy appears to provide effective long-term pain relief and acceptable quality of life in appropriately selected patients with chronic pancreatitis and intractable pain.


Pain, Intractable/prevention & control , Pancreaticoduodenectomy , Pancreatitis, Chronic/surgery , Quality of Life , Adult , Aged , Chronic Disease , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Management , Pain, Intractable/diagnosis , Pain, Intractable/etiology , Pancreatitis, Chronic/complications , Patient Selection , Surveys and Questionnaires , Time Factors , Treatment Outcome
20.
HPB (Oxford) ; 17(10): 909-18, 2015 Oct.
Article En | MEDLINE | ID: mdl-26294338

BACKGROUND: Elderly patients undergoing open pancreatoduodenectomy (OPD) are at increased risk for surgical morbidity and mortality. Whether totally laparoscopic pancreatoduodenectomy (TLPD) mitigates these risks has not been evaluated. METHODS: A retrospective review of outcomes in patients submitted to pancreatoduodenectomy during 2007-2014 was conducted (n = 860). Outcomes in elderly patients (aged ≥70 years) were compared with those in non-elderly patients with respect to risk-adjusted postoperative morbidity and mortality. Differences in outcomes between patients submitted to OPD and TLPD, respectively, were evaluated in the elderly subgroup. RESULTS: In elderly patients, the incidences of cardiac events (odds ratio [OR] 3.21, P < 0.001), respiratory events (OR 1.68, P = 0.04), delayed gastric emptying (DGE) (OR 1.73, P = 0.003), increased length of stay (LoS, 1 additional day) (P < 0.001), discharge disposition other than home (OR 8.14, P < 0.001) and blood transfusion (OR 1.48, P = 0.05) were greater than in non-elderly patients. Morbidity and mortality did not differ between the OPD and TLPD subgroups of elderly patients. In elderly patients, OPD was associated with increased DGE (OR 1.80, P = 0.03), LoS (1 additional day; P < 0.001) and blood transfusion (OR 2.89, P < 0.001) compared with TLPD. CONCLUSIONS: Elderly patients undergoing TLPD experience rates of mortality, morbidity and cardiorespiratory events similar to those in patients submitted to OPD. In elderly patients, TLPD offers benefits by decreasing DGE, LoS and blood transfusion requirements.


Laparoscopy/methods , Pancreaticoduodenectomy/methods , Postoperative Complications/epidemiology , Risk Assessment , Age Factors , Aged , Female , Follow-Up Studies , Humans , Laparoscopy/adverse effects , Length of Stay/trends , Male , Middle Aged , Minnesota/epidemiology , Morbidity/trends , Pancreaticoduodenectomy/adverse effects , Retrospective Studies , Risk Factors , Survival Rate/trends , Treatment Outcome
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