Concepts and techniques for revascularization of replaced hepatic arteries in pancreatic head resections.

BACKGROUND: The relationship of pancreatic ductal adenocarcinoma (PDAC) to important peripancreatic vasculature dictates resectability. As per the current guidelines, tumors with extensive, unreconstructible venous or arterial involvement are staged as unresectable locally advanced pancreatic cancer (LAPC). The introduction of effective multiagent chemotherapy and development of surgical techniques, have renewed interest in local control of PDAC. High-volume centers have demonstrated safe resection of short-segment encasement of the common hepatic artery. Knowledge of the unique anatomy of the patient's vasculature is important in surgical planning of these complex resections. Hepatic artery anomalies are common and insufficient knowledge can result in iatrogenic vascular injury during surgery. METHODS AND RESULTS: Here, we discuss different strategies to resect and reconstruct replaced hepatic arteries during pancreatectomy for PDAC to ensure restoration of adequate blood flow to the liver. Strategies include various arterial transpositions, in-situ interposition grafts and the use of extra-anatomic jump grafts. CONCLUSION: These surgical techniques allow more patients to undergo the only available curative treatment currently available for PDAC. Moreover, these improvements in surgical techniques highlight the shortcoming of current resectability criteria, which rely mainly on local tumor involvement and technical resectability, and disregards tumor biology.

Multiinstitutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas.

OBJECTIVE: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. SUMMARY OF BACKGROUND DATA: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). METHODS: This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. RESULTS: Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. CONCLUSIONS: This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

Multimodal radiomics and cyst fluid inflammatory markers model to predict preoperative risk in intraductal papillary mucinous neoplasms.

Purpose: Our paper contributes to the burgeoning field of surgical data science. Specifically, multimodal integration of relevant patient data is used to determine who should undergo a complex pancreatic resection. Intraductal papillary mucinous neoplasms (IPMNs) represent cystic precursor lesions of pancreatic cancer with varying risk for malignancy. We combine previously defined individual models of radiomic analysis of diagnostic computed tomography (CT) with protein markers extracted from the cyst fluid to create a unified prediction model to identify high-risk IPMNs. Patients with high-risk IPMN would be sent for resection, whereas patients with low-risk cystic lesions would be spared an invasive procedure. Approach: Retrospective analysis of prospectively acquired cyst fluid and CT scans was undertaken for this study. A predictive model combining clinical features with a cyst fluid inflammatory marker (CFIM) was applied to patient data. Quantitative imaging (QI) features describing radiomic patterns predictive of risk were extracted from scans. The CFIM model and QI model were combined into a single predictive model. An additional model was created with tumor-associated neutrophils (TANs) assessed by a pathologist at the time of resection. Results: Thirty-three patients were analyzed (7 high risk and 26 low risk). The CFIM model yielded an area under the curve (AUC) of 0.74. Adding the QI model improved performance with an AUC of 0.88. Combining the CFIM, QI, and TAN models further increased performance to an AUC of 0.98. Conclusions: Quantitative analysis of routinely acquired CT scans combined with CFIMs provides accurate prediction of risk of pancreatic cancer progression. Although a larger cohort is needed for validation, this model represents a promising tool for preoperative assessment of IPMN.

Surgical Residents as Certified Bilingual Speakers: A Quality Improvement Initiative.

BACKGROUND: The objective of this quality improvement initiative was to identify general surgery residents proficient in a non-English language and have each attempt the Clinician Cultural and Linguistic Assessment (CCLA) to become qualified bilingual staff speakers. METHODS: General surgery house staff were asked to self-identify as proficient in a language other than English. Fees for the certification examination were waived, and each resident was excused from clinical duties to complete the exam. McNemar's test was used for statistical analysis. RESULTS: All residents responded to the initial survey, with 18/65 reporting a non-English language proficiency. Of the 12 residents who sat for the CCLA exam, 9 (75.0%) passed, with 5 certifying in the most commonly spoken non-English languages at this institution. The number of certified residents increased from 1 to 10 (1.5 % to 15.4%, p = 0.004). CONCLUSION: Language barriers result in health care disparities for patients with limited English proficiency. This reproducible quality improvement initiative significantly increased the number of qualified bilingual speakers, while 25.0% of self-described proficient speakers did not demonstrate adequate language proficiency. These newly certified providers allow for increased language concordant care, which may be associated with improved outcomes.

Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions.

BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.

Endoscopic versus percutaneous drainage of post-operative peripancreatic fluid collections following pancreatic resection.

BACKGROUND: Post-operative peripancreatic fluid collection (PFC) is a common complication following pancreatic resection which can be managed with endoscopic or percutaneous drainage. METHODS: Patients who underwent either endoscopic or percutaneous drainage of post-operative PFC were extracted from a prospectively-maintained database. The two groups were matched for surgery type, presence of a surgical drain and timing of drainage. RESULTS: Thirty-nine matched patients were identified in each group with a median age of 62 years. For primary drainage, technical success was achieved in almost all patients in both endoscopic and percutaneous groups (100% and 97%, p = NS); clinical success was achieved in 67% and 59%, respectively (p = 0.63). At least one "salvage" drainage procedure was required in 13 endoscopic patients versus 16 in the percutaneous group. Clinical success was achieved following the first salvage. Procedure in 85% of the endoscopic patients and 88% of the percutaneous patients (p = 0.62). Stent/drain duration (59 vs 33 days, p < 0.001) and number of post-procedural CT studies (2 vs 1, p = 0.02) were significantly higher in the endoscopic group. There was no difference in length of stay, complication, or recurrence between the two groups. CONCLUSION: Endoscopic drainage of post-operative PFC appears to be safe and effective with comparable success rates and outcomes to percutaneous drainage.

Progression Patterns in the Remnant Pancreas after Resection of Non-Invasive or Micro-Invasive Intraductal Papillary Mucinous Neoplasms (IPMN).

BACKGROUND: Although IPMN are thought to represent a whole-gland disease, segmental resection remains the most frequently performed treatment. We sought to determine the rates, patterns, and predictors of IPMN progression in the pancreatic remnant following segmental resection of noninvasive or microinvasive IPMN. METHODS: A prospectively maintained database was queried to identify all patients who underwent resection of noninvasive or microinvasive IPMN (≤ 10 mm of invasive component) between 1989 and 2015. Progression (recurrence) was defined as either the development of cancer, a new IPMN cystic lesion > 1 cm or ≥ 50% increase in the diameter of residual IPMN lesions in the remnant. Univariate and multivariate cox regression models were created to determine predictors of progression. RESULTS: A total of 319 patients underwent resection for noninvasive and microinvasive IPMN. The median age was 68, 53% had branch-duct (BD) IPMN, and 6% had microinvasive disease. After a median follow-up of 42 months, 71 patients (22%) experienced IPMN progression. Within this group of 71 patients, 11 (16% of recurrence) developed invasive cancer in the pancreatic remnant after a median of 28 months. Twelve patients (17%) experienced progression > 5 years following initial resection. On multivariate analysis, a distal location of the initial lesion was associated with an increased risk of progression (multivariate hazards ratio = 2.43, confidence interval 1.47-4.0, p < 0.001). CONCLUSIONS: In this study, 22% of patients had disease progression following resection of noninvasive or microinvasive IPMN; 16% of these progressions represented invasive disease. These patients represent a high-risk group and should undergo long-term radiographic surveillance.

Development and Validation of a Multi-institutional Preoperative Nomogram for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas: A Report from The Pancreatic Surgery Consortium.

OBJECTIVE: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset. SUMMARY BACKGROUND DATA: IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. METHODS: Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. RESULTS: We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. CONCLUSIONS: For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.

Multi-institutional Validation Study of Pancreatic Cyst Fluid Protein Analysis for Prediction of High-risk Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: Preliminary work by our group suggested that proteins within the pancreatic cyst fluid (CF) may discriminate degree of IPMN dysplasia. We sought to externally validate these markers and determine whether their inclusion in a preoperative clinical nomogram could increase diagnostic accuracy. SUMMARY BACKGROUND DATA: IPMN is the most common radiographically identifiable precursor to pancreatic cancer; however, the timing and frequency of its malignant progression are unknown, and there are currently no reliable preoperative tests that can determine the grade of dysplasia in IPMN. METHODS: Clinical and radiographic data, as well as CF samples, were obtained from 149 patients who underwent resection for IPMN at 1 of 3 institutions. High-risk disease was defined as the presence of high-grade dysplasia or invasive carcinoma. Multianalyte bead array analysis (Luminex) of CF was performed for 4 protein markers that were previously associated with high-risk disease. Logistic regression models were fit on training data, with and without adjustment for a previously developed clinical nomogram and validated with an external testing set. The models incorporating clinical risk score were presented graphically as nomograms. RESULTS: Within the group of 149 resected patients, 89 (60%) had low-risk disease, and 60 (40%) had high-risk disease. All 4 CF markers (MMP9, CA72-4, sFASL, and IL-4) were overexpressed in patients with high-risk IPMN (P < 0.05). Two predictive models based on preselected combinations of CF markers had concordance indices of 0.76 (Model-1) and 0.80 (Model-2). Integration of each CF marker model into a previously described clinical nomogram leads to increased discrimination compared with either the CF models or nomogram alone (c-indices of 0.84 and 0.83, respectively). CONCLUSIONS: This multi-institutional study validated 2 CF protein marker models for preoperative identification of high-risk IPMN. When combined with a clinical nomogram, the ability to predict high-grade dysplasia was even stronger.

Intraductal Papillary Mucinous Neoplasm of the Pancreas in Young Patients: Tumor Biology, Clinical Features, and Survival Outcomes.

AIM: The aim of this paper is to describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in young patients. METHODS: We evaluated 1693 patients from the Pancreatic Surgery Consortium who underwent resection for IPMN and classified them as younger or older than 50 years of age at the time of surgery. We assessed the relationship of age with clinical, radiological, pathological, and prognostic features. RESULTS: We identified 90 (5%) young patients. Age was not associated with differences in main pancreatic duct size (P = 0.323), presence of solid components (P = 0.805), or cyst size (P = 0.135). IPMNs from young patients were less likely to be of gastric type (37 vs. 57%, P = 0.005), and more likely to be of oncocytic (15 vs. 4%, P = 0.003) and intestinal types (44 vs. 26%, P = 0.004). Invasive carcinomas arising from IPMN were less common in young patients (17 vs. 27%, P = 0.044), and when present they were commonly of colloid type (47 vs. 31% in older patients, P = 0.261) and had better overall survival than older patients (5-year, 71 vs. 37%, log-rank P = 0.031). CONCLUSION: Resection for IPMN is infrequent in young patients, but when they are resected, IPMNs from young patients demonstrate different epithelial subtypes from those in older patients and more favorable prognosis.

Therapeutic Approach to Cystic Neoplasms of the Pancreas.

Management of cystic neoplasms of the pancreas is challenging as it relies on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions, however their ability to predict malignancy is limited. While asymptomatic serous cystadenomas can be managed conservatively, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are more difficult to manage. A selective approach, based on the preoperative likelihood of high-grade dysplasia or invasive disease, is the standard of care. Research is focusing on the development of pre-operative markers for identifying high risk lesions, which will spare patients with low-risk or benign lesions the risks of pancreatectomy.

Stage III pancreatic cancer and the role of irreversible electroporation.

About a third of patients with pancreatic cancer present with locally advanced disease that is not amenable to resection. Because these patients have localized disease, conventional ablative therapies (thermal ablation and cryoablation) have the potential to be beneficial, but their use is inherently limited in the pancreas. These limitations could be overcome by irreversible electroporation-a novel, non-thermal ablative method that is gaining popularity for the treatment of many soft tissue tumors, including those of the pancreas. This review summarizes the status of this technique in the treatment of locally advanced pancreatic cancer. Most of the evidence on efficacy and safety is based on non-randomized prospective series, which show that irreversible electroporation may improve overall survival and pain control in locally advanced pancreatic cancer. As experience with this procedure increases, randomized controlled trials are needed to document its efficacy in locally advanced pancreatic cancer more precisely.