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AGA Guidelines for the Management of Pancreatic Cysts [Comment]

Lennon, Anne Marie; Ahuja, Nita; Wolfgang, Christopher L
PMID: 26231607
ISSN: 1528-0012
CID: 4743402

Technical risk factors for portal vein reconstruction thrombosis in pancreatic resection

Glebova, Natalia O; Hicks, Caitlin W; Piazza, Kristen M; Abularrage, Christopher J; Cameron, Andrew M; Schulick, Richard D; Wolfgang, Christopher L; Black, James H
OBJECTIVE:Vascular reconstruction can facilitate pancreas tumor resection, but optimal methods of reconstruction are not well studied. We report our results for portal vein reconstruction (PVR) for pancreatic resection and determinants of postoperative patency. METHODS:We identified 173 patients with PVR in a prospective database of 6522 patients who underwent pancreatic resection at our hospital from 1970 to 2014. There were 128 patients who had >1 year of follow-up with computed tomography imaging. Preoperative, intraoperative, and postoperative factors were recorded. Patients with and without postoperative PVR thrombosis were compared by univariable, multivariable, and receiver operating characteristic curve analyses. RESULTS:The survival of patients was 100% at 1 month, 88% at 6 months, 66% at 1 year, and 39% on overall median follow-up of 310 days (interquartile range, 417 days). Median survival was 15.5 months (interquartile range, 25 months); 86% of resections were for cancer. Four types of PVR techniques were used: 83% of PVRs were performed by primary repair, 8.7% with interposition vein graft, 4.7% with interposition prosthetic graft, and 4.7% with patch. PVR patency was 100% at 1 day, 98% at 1 month, 91% at 6 months, and 83% at 1 year. Patients with PVR thrombosis were not significantly different from patients with patent PVR in age, survival, preoperative comorbidities, tumor characteristics, perioperative blood loss or transfusion, or postoperative complications. They were more likely to have had preoperative chemotherapy (53% vs 9%; P < .0001), radiation therapy (35% vs 2%; P < .0001), and prolonged operative time (618 ± 57 vs 424 ± 20 minutes; P = .002) and to develop postoperative ascites (76% vs 22%; P < .001). Among patients who developed ascites, 38% of those with PVR thrombosis did so in the setting of tumor recurrence at the porta detected on imaging, whereas among patients with patent PVR, 50% did so (P = .73). Patients with PVR thrombosis were more likely to have had prosthetic graft placement compared with patients with patent PVRs (18% vs 2.7%; P = .03; odds ratio [OR], 7.7; 95% confidence interval [CI], 1.4-42). PVR patency overall was significantly worse for patients who had an interposition prosthetic graft reconstruction (log-rank, P = .04). On multivariable analysis, operative time (OR, 1.01; 95% CI, 1.01-1.02) and prosthetic graft placement (OR, 8.12; 95% CI, 1.1-74) were independent predictors of PVR thrombosis (C statistic = 0.88). CONCLUSIONS:Long operative times and use of prosthetic grafts for reconstruction are risk factors for postoperative portal vein thrombosis. Primary repair, patch, or vein interposition should be preferentially used for PVR in the setting of pancreatic resection.
PMID: 25953018
ISSN: 1097-6809
CID: 4743342

The impact of resident involvement on surgical outcomes among patients undergoing hepatic and pancreatic resections

Ejaz, Aslam; Spolverato, Gaya; Kim, Yuhree; Wolfgang, Christopher L; Hirose, Kenzo; Weiss, Matthew; Makary, Martin A; Pawlik, Timothy M
BACKGROUND:Resident participation during hepatic and pancreatic resections varies. The impact of resident participation on surgical outcomes in hepatic and pancreatic operations is poorly defined. METHODS:We identified 25,511 patients undergoing a hepatic or pancreatic resection between 2006 and 2012 using the American College of Surgeons National Surgical Quality Improvement Program database. Multivariate regression models were constructed to determine any association between resident participation and surgical outcomes. RESULTS:Pancreatic resections (n = 16,045; 62.9%) were more common than liver resections (n = 9,466; 37%). Residents participated in the majority of cases (n = 21,857; 86%), with most involvement at the senior level (postgraduate year ≥ 3, n = 21,147; 97%). Resident participation resulted in slightly longer mean operative times (hepatic, 9 minutes; pancreatic, 22 minutes; both P < .01). Need for perioperative transfusion, hospital duration of stay, and reoperation rates were unaffected by resident participation (all P > .05). Resident participation resulted in a higher risk of overall morbidity (odds ratio [OR], 1.14; 95% CI, 1.05-1.24; P = .001), but not major morbidity (OR, 1.05; 95% CI, 0.93-1.20; P = .40) after liver and pancreas resection. Resident participation resulted in lower odds of 30-day mortality after liver and pancreas resections (OR, 0.75; 95% CI, 0.60-0.94; P = .01). CONCLUSION/CONCLUSIONS:Although resident participation resulted in slightly longer operative times and a modest increase in overall complications after liver and pancreatic resection, other metrics such as duration of stay, major morbidity, and mortality were unaffected. These data have important implications for educating patients regarding resident participation in these complex cases.
PMCID:4695984
PMID: 26003913
ISSN: 1532-7361
CID: 4743362

Quality assessment of the guidelines on cystic neoplasms of the pancreas

Falconi, Massimo; Crippa, Stefano; Chari, Suresh; Conlon, Kevin; Kim, Sun-Whe; Levy, Philippe; Tanaka, Masao; Werner, Jens; Wolfgang, Christopher L; Pezzilli, Raffaele; Castillo, Carlos Fernandez-Del
BACKGROUND:Though cystic pancreatic neoplasms (CPNs) are being increasingly detected, their evaluation and management are still debated and have lead to publication of multiple guidelines for diagnostic work-up, indications for resection, and non-operative management with follow-up strategies of CPNs. AIMS/OBJECTIVE:To analyze available guidelines in order to evaluate their overall quality and clinical applicability, indications for surgical resection and its extent, modalities and timing of follow-up when non-operative management is indicated. METHODS:After a systematic search of the English literature, we selected eight guidelines for assessment according to the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) II instrument. RESULTS:One guideline received the lower AGREE score regarding the "scope and purpose", "rigor of development" and "clarity and presentation" domains, whereas one received the best score for "stakeholder involvement" domain. No differences were found among different guidelines regarding the "applicability". The overall quality assessment score showed that only two guidelines were significantly lower than the others. According to the practical utilization recommendation score, four guidelines were considered as having full applicability in clinical practice. CONCLUSION/CONCLUSIONS:Existing guidelines provide adequate guidance, at least with the present knowledge, for the management of cystic pancreatic lesions; however, not any one was satisfactory to all aspects related to the management of CPN. An update of the existing guidelines should be considered if and when more evidence-based data are available.
PMID: 26100659
ISSN: 1424-3911
CID: 4743382

Pancreatic cancer surgery: past, present, and future

Griffin, James F; Poruk, Katherine E; Wolfgang, Christopher L
The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.
PMCID:4560737
PMID: 26361403
ISSN: 1000-9604
CID: 4743462

Comparison of postoperative complications between internal and external pancreatic duct stenting during pancreaticoduodenectomy: a meta-analysis

Ke, Fa-Yong; Wu, Xiang-Song; Zhang, Yong; Zhang, Hong-Cheng; Weng, Ming-Zhe; Liu, Ying-Bin; Wolfgang, Christopher; Gong, Wei
BACKGROUND:Two types of pancreatic duct stents are used to improve postoperative outcomes of pancreatic anastomosis. The aim of this meta-analysis was to evaluate and compare the postoperative outcomes of patients with internal or external stenting during pancreaticoduodenectomy (PD). METHODS:We searched PubMed, EMBASE, the Cochrane Library and Web of Science databases until the end of December, 2014. Studies comparing outcomes of external vs. internal stent placement in PD were eligible for inclusion. Included literature was extracted and assessed by two independent reviewers. RESULTS:Seven articles were identified for inclusion: three randomized controlled trials (RCTs) and four observational clinical studies (OCS). The meta-analyses revealed that use of external stents had advantage on reducing the incidences of pancreatic fistula (PF) in total [odds ratio (OR) =0.69; 95% confidence interval (CI), 0.48-0.99; P=0.04], PF in soft pancreas (OR =0.30; 95% CI, 0.16-0.56; P=0.0002) and delayed gastric emptying (DGE) (OR =0.58; 95% CI, 0.38-0.89; P=0.01) compared with internal stents. There were no significant differences in other postoperative outcomes between two stenting methods, including postoperative morbidity (OR =0.93; 95% CI, 0.39-2.23; P=0.88), overall mortality (OR =0.70; 95% CI, 0.22-2.25; P=0.55), and intra-abdominal collections (OR =0.67; 95% CI, 0.26-1.71; P=0.40). CONCLUSIONS:Based upon this meta-analysis, the use of external pancreatic stents might have potential benefit in reducing the incidence of PF and DGE. Due to the limited number of original studies, more RCTs are needed to further support our result and clarify the issue.
PMCID:4560740
PMID: 26361409
ISSN: 1000-9604
CID: 4743472

The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single-Institution Experience

Moningi, Shalini; Dholakia, Avani S; Raman, Siva P; Blackford, Amanda; Cameron, John L; Le, Dung T; De Jesus-Acosta, Ana M C; Hacker-Prietz, Amy; Rosati, Lauren M; Assadi, Ryan K; Dipasquale, Shirl; Pawlik, Timothy M; Zheng, Lei; Weiss, Matthew J; Laheru, Daniel A; Wolfgang, Christopher L; Herman, Joseph M
BACKGROUND:Stereotactic body radiation therapy (SBRT) is a promising option for patients with pancreatic cancer (PCA); however, limited data support its efficacy. This study reviews our institutional experience of SBRT in the treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA. METHODS:Charts of all PCA patients receiving SBRT at our institution from 2010 to 2014 were reviewed. Most patients received pre-SBRT chemotherapy. Primary endpoints included overall survival (OS) and local progression-free survival (LPFS). Patients received a total dose of 25-33 Gy in five fractions. RESULTS:A total of 88 patients were included in the analysis, 74 with LAPC and 14 with BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively. Median OS from date of diagnosis was 18.4 months (LAPC, 18.4 mo; BRPC, 14.4 mo) and median PFS was 9.8 months (95 % CI 8.0-12.3). Acute toxicity was minimal with only three patients (3.4 %) experiencing acute grade ≥3 toxicity. Late grade ≥2 gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin-negative resections. CONCLUSIONS:Chemotherapy followed by SBRT in patients with LAPC and BRPC resulted in minimal acute and late toxicity. A large proportion of patients underwent surgical resection despite limited radiographic response to therapy. Further refinements in the integration of chemotherapy, SBRT, and surgery might offer additional advancements toward optimizing patient outcomes.
PMCID:4459890
PMID: 25564157
ISSN: 1534-4681
CID: 4743172

Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma

Schueneman, A; Goggins, M; Ensor, J; Saka, B; Neishaboori, N; Lee, S; Maitra, A; Varadhachary, G; Rezaee, N; Wolfgang, C; Adsay, V; Wang, H; Overman, M J
BACKGROUND:Outcomes for ampullary adenocarcinomas are heterogeneous, and numerous methods of categorisation exist. A histomolecular phenotype based on histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We attempt to validate this classification in a large patient population. METHODS:Tissue samples from 163 patients with resected ampullary adenocarcinoma were classified based on histology and immunohistochemical expression of CDX2 and MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a sample with pancreaticobiliary histology, positive MUC1 and negative CDX2 expression. RESULTS:There were 82 deaths; median follow-up of 32.4 months; and median overall survival of 87.7 (95% CI 42.9-109.5) months. PB comprised 28.2% of the cases. Factors associated with overall survival were histological subtype (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT) vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was statistically significant, although MUC1 positivity defined as ⩾10% staining was significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR 2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival. CONCLUSIONS:The prognostic ability of histomolecular phenotype has been validated in an independent cohort of ampullary adenocarcinoma patients.
PMCID:4647538
PMID: 25989273
ISSN: 1532-1827
CID: 5894132

The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma

Wild, Aaron T; Ye, Xiaobu; Ellsworth, Susannah G; Smith, Jessica A; Narang, Amol K; Garg, Tanu; Campian, Jian; Laheru, Daniel A; Zheng, Lei; Wolfgang, Christopher L; Tran, Phuoc T; Grossman, Stuart A; Herman, Joseph M
OBJECTIVES/OBJECTIVE:Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affects clinical outcomes. METHODS:A retrospective analysis of patients with LAPC treated with chemoradiation at a single institution from 1997 to 2011 was performed. Total lymphocyte counts (TLCs) were recorded at baseline and then monthly during and after chemoradiation. The correlation between treatment-induced lymphopenia, established prognostic factors, and overall survival was analyzed using univariate Cox regression analysis. Important factors identified by univariate analysis were selected as covariates to construct a multivariate proportional hazards model for survival. RESULTS:A total of 101 patients met eligibility criteria. TLCs were normal in 86% before chemoradiation. The mean reduction in TLC per patient was 50.6% (SD, 40.6%) 2 months after starting chemoradiation (P<0.00001), and 46% had TLC<500 cells/mm. Patients with TLC<500 cells/mm 2 months after starting chemoradiation had inferior median survival (8.7 vs. 13.3 mo, P=0.03) and PFS (4.9 vs. 9.0 mo, P=0.15). Multivariate analysis revealed TLC<500 cells/mm to be an independent predictor of inferior survival (HR=2.879, P=0.001) along with baseline serum albumin (HR=3.584, P=0.0002), BUN (HR=1.060, P=0.02), platelet count (HR=1.004, P=0.005), and radiation planning target volume (HR=1.003, P=0.0006). CONCLUSIONS:Severe treatment-related lymphopenia occurs frequently after chemoradiation for LAPC and is an independent predictor of inferior survival.
PMCID:3991773
PMID: 23648440
ISSN: 1537-453x
CID: 4742522

Duodenal neuroendocrine tumors: retrospective evaluation of CT imaging features and pattern of metastatic disease on dual-phase MDCT with pathologic correlation

Tsai, Salina D; Kawamoto, Satomi; Wolfgang, Christopher L; Hruban, Ralph H; Fishman, Elliot K
PURPOSE/OBJECTIVE:The purpose of the study is to evaluate the CT appearance and pattern of metastatic disease of patients with surgically resected well-differentiated duodenal neuroendocrine tumors who underwent pre-operative dual-phase CT. METHODS:Clinical and pathologic records and CT images of 28 patients (average age 58.0 years) following Whipple procedure were retrospectively reviewed. The size, morphology (polypoid, intraluminal mass or wall thickening, intramural mass), location, CT attenuation in the arterial and venous phases, and the presence of lymph node or liver metastases were recorded. RESULTS:On CT, 19 patients (67.8%) had neuroendocrine tumors manifested as polypoid or intraluminal masses (38 lesions, multiple tumors in 3 patients), 4 patients (14.3%) had tumors manifested as wall thickening or intramural masses, and in 5 patients (17.9%), the primary tumor was not visualized. Lesions not seen at CT were less than 0.8 cm on pathologic diagnosis. The mean size of polypoid tumors on CT was 1.2 cm (range 0.3-3.8 cm); 24 tumors were 1.0 cm or smaller, and 14 tumors were larger than 1.0 cm. Most lesions were hypervascular in the arterial phase (19/23 patients) with an increase in tumor enhancement in the venous phase in 14 patients (60.9%), decrease in enhancement in 7 patients (30.4%), and no change in enhancement in 2 patients (8.7%). Thirteen patients (46.4%) had metastatic disease from carcinoid tumor, most commonly regional enhancing lymphadenopathy. CONCLUSION/CONCLUSIONS:Duodenal carcinoid tumors commonly appear as an enhancing mass in either the arterial or venous phases. If a primary tumor is not seen in the duodenum, adjacent enhancing lymphadenopathy can be a clue to the presence of a duodenal carcinoid tumor.
PMCID:4450119
PMID: 25504375
ISSN: 1432-0509
CID: 4743122