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The Role of Intraoperative Pancreatoscopy in the Surgical Management of Intraductal Papillary Mucinous Neoplasms: A Scoping Review

Grewal, Mahip; Habib, Joseph R; Paluszek, Olivia; Cohen, Steven M; Wolfgang, Christopher L; Javed, Ammar A
OBJECTIVES/OBJECTIVE:Most patients with intraductal papillary mucinous neoplasms (IPMNs) are diagnosed with a solitary lesion; however, the presence of skip lesions, not appreciable on imaging, has been described. Postoperatively, these missed lesions can continue to grow and potentially become cancerous. Intraoperative pancreatoscopy (IOP) may facilitate detection of such skip lesions in the remnant gland. The aim of this scoping review was to appraise the evidence on the role of IOP in the surgical management of IPMNs. MATERIALS AND METHODS/METHODS:Studies reporting on the use of IOP during IPMN surgery were identified through searches of the PubMed, Embase, and Scopus databases. Data extracted included IOP findings, surgical plan modifications, and patient outcomes. The primary outcome of interest was the utility of IOP in surgical decision making. RESULTS:Ten studies reporting on the use of IOP for IPMNs were identified, representing 147 patients. A total of 46 skip lesions were identified by IOP. Overall, surgical plans were altered in 37% of patients who underwent IOP. No IOP-related complications were reported. CONCLUSIONS:The current literature suggests a potential role of integration of IOP into the management of patients with IPMNs. This tool is safe and feasible and can result in changes in surgical decision making.
PMID: 38277399
ISSN: 1536-4828
CID: 5625432

Anatomical and Biological Considerations to Determine Resectability in Pancreatic Cancer

Rompen, Ingmar F; Habib, Joseph R; Wolfgang, Christopher L; Javed, Ammar A
Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer.
PMCID:10854859
PMID: 38339242
ISSN: 2072-6694
CID: 5632152

Outcomes after distal pancreatectomy with or without splenectomy for intraductal papillary mucinous neoplasm: international multicentre cohort study

Gorris, Myrte; van Bodegraven, Eduard A; Abu Hilal, Mohammad; Bolm, Louisa; Busch, Olivier R; Del Chiaro, Marco; Habib, Joseph; Hasegawa, Kiyoshi; He, Jin; van Hooft, Jeanin E; Jang, Jin-Young; Javed, Ammar A; Kazami, Yusuke; Kwon, Wooil; Lee, Mirang; Liu, Rong; Motoi, Fuyuhiko; Perri, Giampaolo; Saiura, Akio; Salvia, Roberto; Sasanuma, Hideki; Takeda, Yoshinori; Wolfgang, Christopher; Zelga, Piotr; Castillo, Carlos Fernandez-Del; Marchegiani, Giovanni; Besselink, Marc G
BACKGROUND:International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN. METHODS:An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy. RESULTS:Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504). CONCLUSION/CONCLUSIONS:This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS.
PMCID:10776207
PMID: 38195084
ISSN: 1365-2168
CID: 5628612

Accurate non-invasive grading of nonfunctional pancreatic neuroendocrine tumors with a CT derived radiomics signature

Javed, Ammar A; Zhu, Zhuotun; Kinny-Köster, Benedict; Habib, Joseph R; Kawamoto, Satomi; Hruban, Ralph H; Fishman, Elliot K; Wolfgang, Christopher L; He, Jin; Chu, Linda C
PURPOSE/OBJECTIVE:The purpose of this study was to develop a radiomics-signature using computed tomography (CT) data for the preoperative prediction of grade of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs). MATERIALS AND METHODS/METHODS:A retrospective study was performed on patients undergoing resection for NF-PNETs between 2010 and 2019. A total of 2436 radiomic features were extracted from arterial and venous phases of pancreas-protocol CT examinations. Radiomic features that were associated with final pathologic grade observed in the surgical specimens were subjected to joint mutual information maximization for hierarchical feature selection and the development of the radiomic-signature. Youden-index was used to identify optimal cutoff for determining tumor grade. A random forest prediction model was trained and validated internally. The performance of this tool in predicting tumor grade was compared to that of EUS-FNA sampling that was used as the standard of reference. RESULTS:A total of 270 patients were included and a fusion radiomic-signature based on 10 selected features was developed using the development cohort (n = 201). There were 149 men and 121 women with a mean age of 59.4 ± 12.3 (standard deviation) years (range: 23.3-85.0 years). Upon internal validation in a new set of 69 patients, a strong discrimination was observed with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.71-0.90) with corresponding sensitivity and specificity of 87.5% (95% CI: 79.7-95.3) and 73.3% (95% CI: 62.9-83.8) respectively. Of the study population, 143 patients (52.9%) underwent EUS-FNA. Biopsies were non-diagnostic in 26 patients (18.2%) and could not be graded due to insufficient sample in 42 patients (29.4%). In the cohort of 75 patients (52.4%) in whom biopsies were graded the radiomic-signature demonstrated not different AUC as compared to EUS-FNA (AUC: 0.69 vs. 0.67; P = 0.723), however greater sensitivity (i.e., ability to accurately identify G2/3 lesion was observed (80.8% vs. 42.3%; P < 0.001). CONCLUSION/CONCLUSIONS:Non-invasive assessment of tumor grade in patients with PNETs using the proposed radiomic-signature demonstrated high accuracy. Prospective validation and optimization could overcome the commonly experienced diagnostic uncertainty in the assessment of tumor grade in patients with PNETs and could facilitate clinical decision-making.
PMID: 37598013
ISSN: 2211-5684
CID: 5619252

Current state of radiomics in hepatobiliary and pancreatic malignancies

Grewal, Mahip; Ahmed, Taha; Javed, Ammar Asrar
Rising in incidence, hepatobiliary and pancreatic (HPB) cancers continue to exhibit dismal long-term survival. The overall poor prognosis of HPB cancers is reflective of the advanced stage at which most patients are diagnosed. Late diagnosis is driven by the often-asymptomatic nature of these diseases, as well as a dearth of screening modalities. Additionally, standard imaging modalities fall short of providing accurate and detailed information regarding specific tumor characteristics, which can better inform surgical planning and sequencing of systemic therapy. Therefore, precise therapeutic planning must be delayed until histopathological examination is performed at the time of resection. Given the current shortcomings in the management of HPB cancers, investigations of numerous noninvasive biomarkers, including circulating tumor cells and DNA, proteomics, immunolomics, and radiomics, are underway. Radiomics encompasses the extraction and analysis of quantitative imaging features. Along with summarizing the general framework of radiomics, this review synthesizes the state of radiomics in HPB cancers, outlining its role in various aspects of management, present limitations, and future applications for clinical integration. Current literature underscores the utility of radiomics in early detection, tumor characterization, therapeutic selection, and prognostication for HPB cancers. Seeing as single-center, small studies constitute the majority of radiomics literature, there is considerable heterogeneity with respect to steps of the radiomics workflow such as segmentation, or delineation of the region of interest on a scan. Nonetheless, the introduction of the radiomics quality score (RQS) demonstrates a step towards greater standardization and reproducibility in the young field of radiomics. Altogether, in the setting of continually improving artificial intelligence algorithms, radiomics represents a promising biomarker avenue for promoting enhanced and tailored management of HPB cancers, with the potential to improve long-term outcomes for patients.
SCOPUS:85180702556
ISSN: 2771-0408
CID: 5630552

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

Floortje van Oosten, A; Al Efishat, Mohammad; Habib, Joseph R; Kinny-Köster, Benedict; Javed, Ammar A; He, Jin; Fishman, Elliot K; Quintus Molenaar, I; Wolfgang, Christopher L
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/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/CONCLUSIONS: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.
PMID: 37419779
ISSN: 1477-2574
CID: 5539522

Radiologists' Expectations of Artificial Intelligence in Pancreatic Cancer Imaging: How Good Is Good Enough?

Chu, Linda C; Ahmed, Taha; Blanco, Alejandra; Javed, Ammar; Weisberg, Edmund M; Kawamoto, Satomi; Hruban, Ralph H; Kinzler, Kenneth W; Vogelstein, Bert; Fishman, Elliot K
BACKGROUND:Existing (artificial intelligence [AI]) tools in radiology are modeled without necessarily considering the expectations and experience of the end user-the radiologist. The literature is scarce on the tangible parameters that AI capabilities need to meet for radiologists to consider them useful tools. OBJECTIVE:The purpose of this study is to explore radiologists' attitudes toward AI tools in pancreatic cancer imaging and to quantitatively assess their expectations of these tools. METHODS:A link to the survey was posted on the www.ctisus.com website, advertised in the www.ctisus.com email newsletter, and publicized on LinkedIn, Facebook, and Twitter accounts. This survey asked participants about their demographics, practice, and current attitudes toward AI. They were also asked about their expectations of what constitutes a clinically useful AI tool. The survey consisted of 17 questions, which included 9 multiple choice questions, 2 Likert scale questions, 4 binary (yes/no) questions, 1 rank order question, and 1 free text question. RESULTS:A total of 161 respondents completed the survey, yielding a response rate of 46.3% of the total 348 clicks on the survey link. The minimum acceptable sensitivity of an AI program for the detection of pancreatic cancer chosen by most respondents was either 90% or 95% at a specificity of 95%. The minimum size of pancreatic cancer that most respondents would find an AI useful at detecting was 5 mm. Respondents preferred AI tools that demonstrated greater sensitivity over those with greater specificity. Over half of respondents anticipated incorporating AI tools into their clinical practice within the next 5 years. CONCLUSION/CONCLUSIONS:Radiologists are open to the idea of integrating AI-based tools and have high expectations regarding the performance of these tools. Consideration of radiologists' input is important to contextualize expectations and optimize clinical adoption of existing and future AI tools.
PMID: 37948357
ISSN: 1532-3145
CID: 5609982

Oncologic resection of pancreatic cancer with isolated liver metastasis: Favorable outcomes in select patients

Nagai, Minako; Wright, Michael J; Ding, Ding; Thompson, Elizabeth D; Javed, Ammar A; Weiss, Matthew J; Hruban, Ralph H; Yu, Jun; Burkhart, Richard A; He, Jin; Cameron, John L; Wolfgang, Christopher L; Burns, William R
BACKGROUND:Patients with pancreatic ductal adenocarcinoma (PDAC) and liver metastasis are treated with palliative chemotherapy, whereas similar patients with metastatic colorectal cancer are considered for aggressive surgery. METHODS:Using an institutional database, PDAC patients undergoing liver resection for isolated metastasis were identified. Their overall survival (OS), treatment factors, and clinicopathological variables associated with survival were also evaluated. RESULTS:Forty-seven patients underwent curative-intent surgery for metastatic PDAC to the liver between 2000 and 2019. Median OS was 21.9 months from diagnosis. Fourteen patients underwent unplanned resection of radiographically occult liver metastasis during pancreatectomy with median OS of 8.7 months. On the other hand, 29 patients received systemic chemotherapy followed by planned resection; this cohort had the most favorable prognosis following aggressive surgery with median OS being 38.1 months from diagnosis and 24.1 months from surgery. Preoperative chemotherapy (HR = 7.1; p = .002) and moderate to well differentiation of the primary tumor (HR = 3.7; p = .003) were associated with prolonged survival in multivariate analysis, whereas lymph node metastases, response to preoperative therapy, number of liver metastasis, and extent of liver surgery were not. CONCLUSIONS:In select patients with PDAC and isolated liver metastasis, curative-intent surgery can result in meaningful survival. This aggressive approach seems most beneficial in patients following induction chemotherapy.
PMID: 36652559
ISSN: 1868-6982
CID: 5419192

Conduits in Vascular Pancreatic Surgery: Analysis of Clinical Outcomes, Operative Techniques and Graft Performance

Kinny-Köster, Benedict; Habib, Joseph R; van Oosten, A Floortje; Javed, Ammar A; Cameron, John L; Burkhart, Richard A; Burns, William R; He, Jin; Wolfgang, Christopher L
OBJECTIVES/OBJECTIVE:We analyze successes and failures of pushing the boundary in vascular pancreatic surgery to establish safety of conduit reconstructions. SUMMARY BACKGROUND DATA/BACKGROUND:Improved systemic control from chemotherapy in pancreatic cancer is increasing the demand for surgical solutions of extensive local vessel involvement, but conduit-specific data are scarce. METHODS:We identified 63 implanted conduits (41% autologous vessels, 37% allografts, 18% PTFE) in 56 pancreatic resections of highly selected cancer patients between October 2013 and July 2020 from our prospectively maintained database. Assessed parameters were survival, perioperative complications, operative techniques (anatomic and extra-anatomic routes) and conduit patency. RESULTS:For vascular reconstruction, 25 arterial and 38 venous conduits were utilized during 39 pancreatoduodenectomies, 14 distal pancreatectomies and 3 total pancreatectomies. The median postoperative survival was 2 years. A Clavien-Dindo grade ≥IIIa complication was apparent in 50% of the patients with a median Comprehensive Complication Index of 29.6. The 90-day mortality in this highly selected cohort was 9%. Causes of mortality were conduit-related in 3 patients, late postpancreatectomy hemorrhage in 1 patient and early liver metastasis in 1 patient. Image-based patency rates of conduits were 66% and 45% at postoperative days 30 and 90, respectively. CONCLUSIONS:Our perioperative mortality of vascular pancreatic surgery with conduits in the arterial or venous system is 9%. Reconstructions are technically feasible with different anatomic and extra-anatomic strategies, while identifying predictors of early conduit occlusion remains challenging. Optimizing reconstructed arterial and venous hemodynamics in the context of pancreatic malignancy will enable long-term survival in more patients responsive to chemotherapies.
PMID: 35838419
ISSN: 1528-1140
CID: 5269442

Grading Pancreatic Neuroendocrine Tumors via Endoscopic Ultrasound-guided Fine Needle Aspiration: A Multi-Institutional Study

Javed, Ammar A; Pulvirenti, Alessandra; Razi, Samrah; Zheng, Jian; Michelakos, Theodoros; Sekigami, Yurie; Thompson, Elizabeth; Klimstra, David S; Deshpande, Vikram; Singhi, Aatur D; Weiss, Matthew J; Wolfgang, Christopher L; Cameron, John L; Wei, Alice C; Zureikat, Amer H; Ferrone, Cristina R; He, Jin
OBJECTIVES/OBJECTIVE:To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade. BACKGROUND:WHO grading system is prognostic in pancreatic neuroendocrine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 60% and 80%. METHODS: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 between c-grade and h-grade and trends of utilization of EUS-FNA were assessed. RESULTS:Of 1,336 patients included, 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). Highest concordance (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 the 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). However, concordance between c-grade and h-grade did not change significantly (p=0.056). CONCLUSION/CONCLUSIONS: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 near-perfect agreement when assessing PanNETs >2 cm in size.
PMID: 35081574
ISSN: 1528-1140
CID: 5154572