Faculty Bibliography

BACKGROUND:The introduction of multi-agent chemotherapy and radiation therapy has facilitated potential resection with curative intent in selected locally advanced pancreatic cancer (LAPC) patients with excellent outcomes. Nevertheless, there remains a remarkable lack of consensus on the management of LAPC. We sought to describe the outcomes of patients with LAPC and objectively define the multidisciplinary selection process for operative exploration based on anatomical factors. METHODS:Consecutive patients with LAPC were evaluated for pancreatic surgery in the multidisciplinary clinic of a high-volume institution, between 2013 and 2018. Prospective stratification (LAPC-1, LAPC-2, and LAPC-3), based on the involvement of regional anatomical structures, was performed at the time of presentation prior to the initiation of treatment. Resection rates and patient outcomes were evaluated and correlated with the initial anatomic stratification system. RESULTS:Overall, 415 patients with LAPC were included in the study, of whom 84 (20%) were successfully resected, with a median overall survival of 35.3 months. The likelihood of operative exploration was associated with the pretreatment anatomic LAPC score, with a resection rate of 49% in patients classified as LAPC-1, 32% in LAPC-2, and 11% in LAPC-3 (p < 0.001). Resected patients with improvement of the LAPC score at the time of exploration had significantly longer median overall survival compared with those with no change or progression of LAPC score (60.7 vs. 29.8 months, p = 0.006). CONCLUSIONS:Selected patients with LAPC can undergo curative-intent surgery with excellent outcomes. The proposed Johns Hopkins anatomic LAPC score provides an objective system to anticipate the probability of eventual surgical resection after induction therapy.

BACKGROUND:The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS:We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS:Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION:These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.

PURPOSE:may also mutate and confer the HR-DDR deficiency in pancreatic ductal adenocarcinoma (PDAC). METHODS:We conducted a study to examine the genetic alterations using a companion diagnostic 15-gene HR-DDR panel in PDACs. HR-DDR gene mutations were identified and characterized by whole-exome sequencing and whole-genome sequencing. Different HR-DDR gene mutations are associated with variable homologous recombination deficiency (HRD) scores. RESULTS:is not the gene panel for germline tests. CONCLUSION:in the germline test of HR-DDR pathway genes.

Introduction: World Health Organization (WHO) grading system is prognostic in pancreatic neuroendocrine tumors (PanNETs). Concordance between WHO-grade on cytology (c-grade) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and histopathological analysis (h-grade) of surgical specimen is reported between 60% and 80%. Factors associated with concordance and trends of utilization of EUS-FNA remain poorly understood.
Method(s): A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance and trends of utilization of EUS-FNA were assessed.
Result(s): Of 1,329 patients, 682 (51.1%) underwent EUS-FNA; 567(83.1%) were diagnostic of PanNETs and WHO-grade was reported for 293 (51.7%) patients. The concordance between c-grade and h-grade was 78.2% with moderate inter-rater agreement (Kc=0.48,p<0.001). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. >=2 cm, 88.9% vs. 72.7%,p=0.001). The highest concordance of 97.9% was observed in patients with small tumors undergoing assessment between 2015-2019 with near perfect inter-rater agreement (Kc=0.88, p<0.001) An increase in utilization of EUS-FNA (46.7% to 62.1%) was observed over the last 2 decades (p<0.001). EUS-FNA was more frequently diagnostic of PanNETs (p<0.001), and WHO-grade was more frequently reported (<0.001). Concordance between c-grade and h-grade did not change significantly (p=0.056).
Conclusion(s): Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with strong agreement when assessing PanNETs >2cm in size.
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Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ("field defect") in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect"may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression; thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.

BACKGROUND:Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. METHODS:A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. RESULTS:Nodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71-7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03-1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63-0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. CONCLUSION/CONCLUSIONS:Our model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.

BACKGROUND:Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare with low-grade malignancy and unclarified clinicopathological features. This study aimed to examine their characteristics and re-evaluate current treatments. METHODS:Databases from three sources were screened for patients with SPNs. We compared the perioperative variables, clinical data, overall survival (OS), and prognostic factors for recurrence among the three corresponding cohorts. RESULTS:We identified 286 patients diagnosed with SPNs between 1988 and 2020. Patients were mostly women (81%; median age: 38 years), and peak incidence was observed in women of 20-29 years of age. SPNs had a peak incidence in Asian men at 50-59 years of age (p = 0.002) and a delayed peak incidence in Asian women at 30-39 years of age (p < 0.001). Treatment strategies differed significantly across the institutions and included variations in the number of harvested lymph nodes and rates of vascular resection. Lymph node positivity was the only predictor of postoperative recurrence (odds ratio, 2.2; 95% confidence interval, 1.38-2.99; p = 0.007). Higher rates of lymphovascular invasion (p = 0.02), perineural invasion (p < 0.001), and R1 margin involvement (p < 0.001), as seen in one institution, did not result in poorer long-term survival in terms of the overall (p = 0.43), SPN-specific (p = 0.69), and recurrence-free survivals (p = 0.067). CONCLUSIONS:In contrast to previous findings that SPNs are prevalent in young women, a racial predilection for middle-aged Asian men and a delayed female peak incidence were noted. Parenchyma-preserving pancreatectomy may be an acceptable treatment. Non-radical surgery may be appropriate in patients with multiple comorbidities.

Background/UNASSIGNED:Recent literature suggests wide variations exist in the international management of locally advanced pancreatic cancer. This study sought to evaluate how geography contributes to variations in management of locally advanced pancreatic cancer. Methods/UNASSIGNED:An electronic survey investigating preferences for the evaluation and management of locally advanced pancreatic cancer was distributed to an international cohort of pancreatic surgeons. Surgeons were classified according to geographic location of practice, and survey responses were compared across locations. Results/UNASSIGNED:A total of 153 eligible responses were received from 4 continents: North and South America (n = 94, 61.4%), Europe (n = 25, 16.3%), and Asia (n = 34, 22.2%). Preferences for the use and duration of neoadjuvant chemotherapy and radiotherapy varied widely. For example, participants in Asia commonly preferred 2 months of neoadjuvant chemotherapy (61.8%), whereas North and South American participants preferred 4 months (52.1%), and responses in Europe were mixed (P = .006). Participants in Asia were less likely to consider isolated liver or lung metastases contraindications to exploration and consequently had a greater propensity to consider exploration in a vignette of oligometastatic disease (56.7% vs North and South America: 25.6%, Europe: 43.5%; P = .007). Conclusion/UNASSIGNED:In an international survey of pancreatic surgeons, attitudes regarding locally advanced pancreatic cancer and metastatic disease management varied widely across geographic locations. Better evidence is needed to define optimal management of locally advanced pancreatic cancer.

PURPOSE/OBJECTIVE:A wide array of benign and malignant lesions of the pancreas can be cystic and these cystic lesions can have overlapping imaging appearances. The purpose of this study is to compare the diagnostic accuracy of a radiomics-based pancreatic cyst classifier to an experienced academic radiologist. METHODS:In this IRB-approved retrospective single-institution study, patients with surgically resected pancreatic cysts who underwent preoperative abdominal CT from 2003 to 2016 were identified. Pancreatic cyst(s) and background pancreas were manually segmented, and 488 radiomics features were extracted. Random forest classification based on radiomics features, age, and gender was evaluated with fourfold cross-validation. An academic radiologist blinded to the final pathologic diagnosis reviewed each case and provided the most likely diagnosis. RESULTS:214 patients were included (64 intraductal papillary mucinous neoplasms, 33 mucinous cystic neoplasms, 60 serous cystadenomas, 24 solid pseudopapillary neoplasms, and 33 cystic neuroendocrine tumors). The radiomics-based machine learning approach showed AUC of 0.940 in pancreatic cyst classification, compared with AUC of 0.895 for the radiologist. CONCLUSION/CONCLUSIONS:Radiomics-based machine learning achieved equivalent performance as an experienced academic radiologist in the classification of pancreatic cysts. The high diagnostic accuracy can potentially maximize the efficiency of healthcare utilization by maximizing detection of high-risk lesions.