Artificial intelligence for assessment of vascular involvement and tumor resectability on CT in patients with pancreatic cancer.

OBJECTIVE: This study aimed to develop and evaluate an automatic model using artificial intelligence (AI) for quantifying vascular involvement and classifying tumor resectability stage in patients with pancreatic ductal adenocarcinoma (PDAC), primarily to support radiologists in referral centers. Resectability of PDAC is determined by the degree of vascular involvement on computed tomography scans (CTs), which is associated with considerable inter-observer variability. METHODS: We developed a semisupervised machine learning segmentation model to segment the PDAC and surrounding vasculature using 613 CTs of 467 patients with pancreatic tumors and 50 control patients. After segmenting the relevant structures, our model quantifies vascular involvement by measuring the degree of the vessel wall that is in contact with the tumor using AI-segmented CTs. Based on these measurements, the model classifies the resectability stage using the Dutch Pancreatic Cancer Group criteria as either resectable, borderline resectable, or locally advanced (LA). RESULTS: We evaluated the performance of the model using a test set containing 60 CTs from 60 patients, consisting of 20 resectable, 20 borderline resectable, and 20 locally advanced cases, by comparing the automated analysis obtained from the model to expert visual vascular involvement assessments. The model concurred with the radiologists on 227/300 (76%) vessels for determining vascular involvement. The model's resectability classification agreed with the radiologists on 17/20 (85%) resectable, 16/20 (80%) for borderline resectable, and 15/20 (75%) for locally advanced cases. CONCLUSIONS: This study demonstrates that an AI model may allow automatic quantification of vascular involvement and classification of resectability for PDAC. RELEVANCE STATEMENT: This AI model enables automated vascular involvement quantification and resectability classification for pancreatic cancer, aiding radiologists in treatment decisions, and potentially improving patient outcomes. KEY POINTS: • High inter-observer variability exists in determining vascular involvement and resectability for PDAC. • Artificial intelligence accurately quantifies vascular involvement and classifies resectability for PDAC. • Artificial intelligence can aid radiologists by automating vascular involvement and resectability assessments.

Trends in access to minimally invasive pancreaticoduodenectomy for pancreatic cancers.

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD), including robotic (RPD) and laparoscopy (LPD), is becoming more frequently employed in the management of pancreatic ductal adenocarcinoma (PDAC), though the majority of operations are still performed via open approach (OPD). Access to technologic advances often neglect the underserved. Whether disparities in access to MIPD exist, remain unclear. METHODS: The National Cancer Database (NCDB) was queried (2010-2020) for patients who underwent pancreatoduodenectomy for PDAC. Cochran-Armitage tests assessed for trends over time. Social determinants of health (SDH) were compared between approaches. Multinomial logistic models identified predictors of MIPD. RESULTS: Of 16,468 patients, 80.03 % underwent OPD and 19.97 % underwent MIPD (22.60 % robotic; 77.40 % laparoscopic). Black race negatively predicted LPD (vs white (OR 0.822; 95 % CI 0.701-0.964)). Predictors of RPD included Medicare/other government insurance (vs uninsured or Medicaid (OR 1.660; 95 % CI 1.123-2.454)) and private insurance (vs uninsured or Medicaid (OR 1.597; 95 % CI 1.090-2.340)). Early (2010-2014) vs late (2015-2020) diagnosis, stratified by race, demonstrated an increase in Non-White patients undergoing OPD (13.15 % vs 14.63 %; p = 0.016), but not LPD (11.41 % vs 13.57 %;p = 0.125) or RPD (14.15 % vs 15.23 %; p = 0.774). CONCLUSION: SDH predict surgical approach more than clinical stage, facility type, or comorbidity status. Disparities in race and insurance coverage are different between surgical approaches.

Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection.

BACKGROUND: Repurposing existing drugs for use in oncology is more efficient, cost-effective and safe than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance. This study assessed the impact of calcium channel blockers (CCB) in pancreatic cancer. METHODS: Retrospective population study of patients undergoing resection (curative intent) of pancreatic ductal adenocarcinoma (SEER-Medicare, 2007-2017). Cox models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, the impact of CCB was assessed separately in patients receiving neoadjuvant chemotherapy. RESULTS: 6,223 patients were included, of whom 660 were prescribed CCB. In total, 591 received neoadjuvant chemotherapy; in this cohort CCB prescription was associated with improved overall survival when adjusting for multiple prognostic factors (aHR = 0.715, 0.514-0.996, P = 0.047). This effect was not observed in patients not receiving neoadjuvant chemotherapy (aHR = 1.082, 0.982-1.191, P = 0.112). CONCLUSION: CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy, mirroring the chemosensitising effect in laboratory studies. This defines patients receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.

Pancreas CT assessment for pancreatic ductal adenocarcinoma resectability: effect of tube voltage and slice thickness on image quality and diagnostic performance.

OBJECTIVES: To assess the resectability of pancreatic ductal adenocarcinoma (PDAC), the evaluation of tumor vascular contact holds paramount significance. This study aimed to compare the image quality and diagnostic performance of high-resolution (HR) pancreas computed tomography (CT) using an 80 kVp tube voltage and a thin slice (1 mm) for assessing PDAC resectability, in comparison with the standard protocol CT using 120 kVp. METHODS: This research constitutes a secondary analysis originating from a multicenter prospective study. All participants underwent both the standard protocol pancreas CT using 120 kVp with 3 mm slice thickness (ST) and HR-CT utilizing an 80 kVp tube voltage and 1 mm ST. The contrast-to-noise ratio (CNR) between parenchyma and tumor, along with the degree of enhancement of the abdominal aorta and main portal vein (MPV), were measured and subsequently compared. Additionally, the likelihood of margin-negative resection (R0) was evaluated using a five-point scale. The diagnostic performance of both CT protocols in predicting R0 resection was assessed through the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 69 patients (37 males and 32 females; median age, 66.5 years) were included in the study. The median CNR of PDAC was 10.4 in HR-CT, which was significantly higher than the 7.1 in the standard CT (P=0.006). Furthermore, HR-CT demonstrated notably higher median attenuation values for both the abdominal aorta (579.5 HU vs. 327.2 HU; P=0.002) and the MPV (263.0 HU vs. 175.6 HU; P=0.004) in comparison with standard CT. Following surgery, R0 resection was achieved in 51 patients. The pooled AUC for HR-CT in predicting R0 resection was 0.727, slightly exceeding the 0.699 of standard CT, albeit lacking a significant statistical distinction (P=0.128). CONCLUSION: While HR pancreas CT using 80 kVp offered a notably greater degree of contrast enhancement in vessels and a higher CNR for PDAC compared to standard CT, its diagnostic performance in predicting R0 resection remained statistically comparable.

Preoperative assessment of peripheral vascular invasion of pancreatic ductal adenocarcinoma based on high-resolution MRI.

OBJECTIVES: Preoperative imaging of vascular invasion is important for surgical resection of pancreatic ductal adenocarcinoma (PDAC). However, whether MRI and CT share the same evaluation criteria remains unclear. This study aimed to compare the diagnostic accuracy of high-resolution MRI (HR-MRI), conventional MRI (non-HR-MRI) and CT for PDAC vascular invasion. METHODS: Pathologically proven PDAC with preoperative HR-MRI (79 cases, 58 with CT) and non-HR-MRI (77 cases, 59 with CT) were retrospectively collected. Vascular invasion was confirmed surgically or pathologically. The degree of tumour-vascular contact, vessel narrowing and contour irregularity were reviewed respectively. Diagnostic criteria 1 (C1) was the presence of all three characteristics, and criteria 2 (C2) was the presence of any one of them. The diagnostic efficacies of different examination methods and criteria were evaluated and compared. RESULTS: HR-MRI showed satisfactory performance in assessing vascular invasion (AUC: 0.87-0.92), especially better sensitivity (0.79-0.86 vs. 0.40-0.79) than that with non-HR-MRI and CT. HR-MRI was superior to non-HR-MRI. C2 was superior to C1 on CT evaluation (0.85 vs. 0.79, P = 0.03). C1 was superior to C2 in the venous assessment using HR-MRI (0.90 vs. 0.87, P = 0.04) and in the arterial assessment using non-HR-MRI (0.69 vs. 0.68, P = 0.04). The combination of C1-assessed HR-MRI and C2-assessed CT was significantly better than that of CT alone (0.96 vs. 0.86, P = 0.04). CONCLUSIONS: HR-MRI more accurately assessed PDAC vascular invasion than conventional MRI and may contribute to operative decision-making. C1 was more applicable to MRI scans, and C2 to CT scans. The combination of C1-assessed HR-MRI and C2-assessed CT outperformed CT alone and showed the best efficacy in preoperative examination of PDAC.

Impact of Biopsy Attempts, Race, and Access on Time to Initiation of Treatment for Pancreatic Cancer.

BACKGROUND: Biopsy of suspected pancreatic cancer (PDAC) in surgical candidates is informative however not always necessary. Biopsies impact treatment options as histological diagnosis are presently required for neo-adjuvant therapy, but not surgical resection. We explored the impact of pursuing tissue diagnosis by endoscopic ultrasound (EUS) biopsy on time to treatment in patients with resectable and borderline resectable PDAC. METHODS: A retrospective review of surgical patients with ultimately proven PDAC was performed (2011-2021). Milestone dates (cancer suspected, biopsy(ies), surgical or neo-adjuvant treatment) were collected. Mann-Whitney-Wilcoxon tests, Pearson's chi-squared tests, Fisher's exact tests, linear regressions, and Cox proportional hazard models were used for data analysis. RESULTS: Among 131 resectable and 58 borderline resectable patients, the borderline resectable group underwent more biopsies (1.2 vs 0.7, p < 0.0001), were more likely to undergo biopsy at tertiary care centers (67.2% vs 30.5%, p < 0.0001), and trended toward longer time to treatment (49 vs 44 days, p = 0.070). Significant increases in days to treatment were seen in patients with Black race (29 days, p = 0.0002) and Medicare insurance (22 days, p = 0.038) and no biopsies at a tertiary care center (10 days, p = 0.039). After adjusting for covariates, additional biopsies significantly delayed treatment (1 biopsy: 21 days, p = 0.0001; 2 biopsies: 44 days, p < 0.0001; 3 biopsies: 68 days, p < 0.0001). CONCLUSIONS: EUS biopsy significantly impacts time between suspicion and treatment of PDAC. This may be exacerbated by clinical practices increasingly favoring neo-adjuvant therapy that necessitates biopsy-proven disease. Time to treatment may also be impacted by access to tertiary centers and racial disparities.

Determination of "borderline resectable" pancreatic cancer - A global assessment of 30 shades of grey.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. Accurate preoperative assessment using computed tomography (CT) to determine resectability is crucial in ensuring patients are offered the most appropriate therapeutic strategy. Despite the use of classification guidelines, any interobserver variability between reviewing surgeons and radiologists may confound decisions influencing patient treatment pathways. METHODS: In this multicentre observational study, an international group of 96 clinicians (42 hepatopancreatobiliary surgeons and 54 radiologists) were surveyed and asked to report 30 pancreatic CT scans of pancreatic cancer deemed borderline at respective multidisciplinary meetings (MDM). The degree of interobserver agreement in resectability among radiologists and surgeons was assessed and subgroup regression analysis was performed. RESULTS: Interobserver variability between reviewers was high with no unanimous agreement. Overall interobserver agreement was fair with a kappa value of 0.32 with a higher rate of agreement among radiologists over surgeons. CONCLUSION: Interobserver variability among radiologists and surgeons globally is high, calling into question the consistency of clinical decision making for patients with PDAC and suggesting that central review may be required for studies of neoadjuvant or adjuvant approaches in future as well as ongoing quality control initiatives, even amongst experts in the field.

Pancreatic Cystic Lesions: Next Generation of Radiologic Assessment.

Pancreatic cystic lesions are frequently identified on cross-sectional imaging. As many of these are presumed branch-duct intraductal papillary mucinous neoplasms, these lesions generate much anxiety for the patients and clinicians, often necessitating long-term follow-up imaging and even unnecessary surgical resections. However, the incidence of pancreatic cancer is overall low for patients with incidental pancreatic cystic lesions. Radiomics and deep learning are advanced tools of imaging analysis that have attracted much attention in addressing this unmet need, however, current publications on this topic show limited success and large-scale research is needed.

Cost-effectiveness of pancreas surveillance: The CDKN2A-p16-Leiden cohort.

BACKGROUND: CDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis. OBJECTIVE: To assess the cost-effectiveness of surveillance, as compared to no surveillance. METHODS: In 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen-detected tumors and on survival. The Kaplan-Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state-transition model was constructed to estimate lifelong outcomes. RESULTS: A total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long-term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by €13,900 per patient, with a cost-utility ratio of €14,000 per quality-adjusted life year gained. For annual surveillance to have an acceptable cost-effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher. CONCLUSION: The tumor could be resected in most patients with a screen-detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost-effective.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Intraoperative Pancreatic Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in the Era of Neoadjuvant Therapy: A Multi-institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting. The impact of neoadjuvant therapy on this practice and its relationship with overall survival (OS) is incompletely understood. METHODS: We reviewed PDAC patients (80% borderline resectable/locally advanced [BR/LA]) undergoing pancreaticoduodenectomy after neoadjuvant therapy at seven, academic, high-volume centers (2010-2018). Multivariable models examined the association of PS:R0, PS:R1, and converted-R0 margins with OS. RESULTS: Of 272 patients receiving at least 2 (median 4) cycles of neoadjuvant chemotherapy (71% mFOLFIRINOX or gemcitabine/nab-paclitaxel) and undergoing pancreaticoduodenectomy with intraoperative frozen-section assessment of the transected pancreatic neck margin, PS:R0 (n = 220, 80.9%) was observed in a majority of patients; 18 patients (6.6%) had converted-R0 margins following additional resection, whereas 34 patients (12.5%) had persistently positive PS:R1 margins. At a median follow-up of 42 months, PS:R0 resection was associated with improved OS compared with either converted-R0 or PS:R1 resection (median 25 vs. 14 vs. 16 months, respectively; p = 0.023), with no survival difference between the converted-R0 and PS:R1 groups (p = 0.9). On Cox regression, SMA margin positivity (hazard ratio 2.2, p = 0.012), but not neck margin positivity (hazard ratio 1.2, p = 0.65), was associated with worse OS. CONCLUSIONS: In this multi-institutional cohort of predominantly BR/LA PDAC patients undergoing pancreaticoduodenectomy following modern neoadjuvant therapy, pursuing a negative neck margin intraoperatively if the initial margin is positive does not appear to be associated with improved survival.

Opportunity Costs of Surgical Resection and Perioperative Chemotherapy for Locoregional Pancreatic Adenocarcinoma.

PURPOSE: Given the perioperative morbidity and intensity of multimodality treatment, patients with resected pancreatic ductal adenocarcinoma (PDAC) spend a substantial amount of time in clinical care. The primary aim was to determine total time spent in multimodality care for patients with locoregional PDAC. METHODS: A cohort study of all patients who underwent curative-intent resection for PDAC at a single-institution, tertiary care center was performed (2015-2019). Exact times for all relevant visits were abstracted from the primary medical record, and travel time was calculated. Care time was divided into preoperative, surgical, radiation, and systemic therapy phases of care. Primary outcome measures were the percentage of total survival time (TST) and percentage of overall survival (OS) days spent in receipt of care. RESULTS: One hundred seven patients were included. Patients spent a median of 5.0% (interquartile range [IQR] 2.4%-10.1%) of TST and 11.0% (IQR, 5.7%-20.4%) of OS days in receipt of clinical care. Preoperative, surgical, radiation, and systemic therapy phases of care comprised a median of 0.9% (IQR, 0.4%-2.2%), 3.0% (IQR, 1.9%-6.8%), 4.4% (IQR, 3.6%-6.3%), and 10.0% (IQR, 6.2%-14.1%) of OS days. The median per-visit travel time was 60 minutes (IQR, 32-120), and the median cumulative travel time was 22.0 hours (IQR, 12.0-51.5). 12.1% (n = 13) and 7.8% (n = 4) of patients spent > 10% of TST in receipt of surgical and systemic therapy care, respectively. CONCLUSION: Patients with locoregional pancreatic cancer spend a considerable percentage of their survival time in receipt of oncologic care. Further research to determine predictors of increased time burden is warranted to better inform shared decision making.

Imaging Assessment of Pancreatic Cancer Resectability After Neoadjuvant Therapy: AJR Expert Panel Narrative Review.

Despite important innovations in the treatment of pancreatic ductal adenocarcinoma (PDAC), PDAC remains a disease with poor prognosis and high mortality. A key area for potential improvement in the management of PDAC, aside from earlier detection in patients with treatable disease, is the improved ability of imaging techniques to differentiate treatment response after neoadjuvant therapy (NAT) from worsening disease. It is well established that current imaging techniques cannot reliably make this distinction. This narrative review provides an update on the imaging assessment of pancreatic cancer resectability after NAT. Current definitions of borderline resectable PDAC, as well as implications for determining likely patient benefit from NAT, are described. Challenges associated with PDAC pathologic evaluation and surgical decision making that are of relevance to radiologists are discussed. Also explored are the specific limitations of imaging in differentiating the response after NAT from stable or worsening disease, including issues relating to protocol optimization, tumor size assessment, vascular assessment, and liver metastasis detection. The roles of MRI as well as PET and/or hybrid imaging are considered. Finally, a short PDAC reporting template is provided for use after NAT. The highlighted methods seek to improve radiologists' assessment of PDAC treatment response after NAT.

Prospective trial to evaluate the prognostic value of different nutritional assessment scores for survival in pancreatic ductal adenocarcinoma (NURIMAS Pancreas SURVIVAL).

BACKGROUND: Malnutrition is associated with poor survival in pancreatic cancer patients. Nutritional scores show great heterogeneity diagnosing malnutrition. The aim of this study was to find the score best suitable to identify patients with malnutrition related to worse survival after surgery for pancreatic ductal adenocarcinoma (PDAC). This study represents a follow-up study to the prospective NURIMAS Pancreas trial that evaluated short term impact of nutritional score results after surgery. METHODS: Risk of malnutrition was evaluated preoperatively using 12 nutritional assessment scores. Patients were followed-up prospectively for at least 3 years. Patients at risk for malnutrition were compared with those not at risk according to each score using Kaplan-Meier survival statistics. RESULTS: A total of 116 patients receiving a PDAC resection in curative intent were included. Malnutrition according to the Subjective Global Assessment score (SGA), the Short Nutritional Assessment Questionnaire (SNAQ), and the INSYST2 score was associated with worse overall survival (SGA: at-risk: 392 days; not at-risk: 942 days; P = 0.001; SNAQ: at-risk: 508 days; not at-risk: 971 days; P = 0.027; INSYST2: at-risk: 538 days; not at risk: 1068; P = 0.049). In the multivariate analysis, SGA (hazard ratio of death 2.16, 95% confidence interval 1.34-3.47, P = 0.002) was associated with worse overall survival. CONCLUSIONS: Malnutrition as defined by the Subjective Global Assessment is independently associated with worse survival in resected PDAC patients. The SGA should be used to stratify PDAC patients in clinical studies. Severely malnourished patients according to the SGA profit from intensified nutritional therapy should be evaluated in a randomized controlled trial.

Peripheral blood and tissue assessment highlights differential tumor-circulatory gradients of IL2 and MIF with prognostic significance in resectable pancreatic ductal adenocarcinoma.

Various reports have pointed out the potential of cytokines as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDA). Nonetheless, the evidence is contradictory and the role of chronic inflammation and relationship between circulatory and corresponding tumoral cytokine levels remain elusive. Utilizing a broad array of cytokines, we identified two opposing parameters: serum levels of interleukin 2 (IL2) and macrophage migration inhibitory factor (MIF) are diagnostic and prognostic factors. While low IL2 levels are associated with PDA, they also relate to a favorable prognosis of patients. In contrast, high MIF levels are associated with PDA and simultaneously related to an unfavorable outcome. MIF levels are associated with the intratumoral density of M2 macrophages (CD163+). Focusing on the tumor-to-serum gradient, we unveiled a different pattern of compartmental cytokine expression between IL2 and MIF. Our findings indicate that an extra-tumoral source of IL2 exists in PDA patients leading to increased detectability in the circulatory system. In case of MIF, the tumor microenvironment is presumably the main site of production and thereby reflected by serum measurements. Taken together, our study describes IL2 and MIF levels as biomarker candidates for diagnosis and prognosis of PDA, highlighting the need for compartmental cytokine analyses. From the perspective of tumor immunobiology, we identify multiple inflammatory states (proposed as types I-III) and see that systemic chronic dysregulation, independent of tumor microenvironment, can be measured and is a possible tool for stratification. Thus, direct correlation of local cytokine levels to peripheral blood levels needs to be regarded with caution.

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology.

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Contemporary Reappraisal of Intraoperative Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Review.

Importance: Although margin-negative (R0) resection is the gold standard for surgical management of localized pancreatic ductal adenocarcinoma (PDAC), the question of how to manage the patient with a microscopically positive intraoperative neck margin (IONM) during pancreaticoduodenectomy remains controversial. Observations: In the absence of randomized clinical trials, we critically evaluated high-quality retrospective studies examining the oncologic utility of re-resecting positive IONMs during pancreaticoduodenectomy for PDAC (2000-2019). Several studies have concluded that additional pancreatic resection to achieve an R0 margin in IONM-positive cases does not influence survival. The largest is a multi-institutional study of 1399 patients undergoing pancreaticoduodenectomy, which demonstrated that in comparison with patients undergoing R0 resection (n = 1196; median survival, 21 months), those with either final R1 resections (n = 131) or undergoing margin conversion from IONM-positive to R0 resection on permanent section (n = 72) demonstrated similar median survival times (13.7 and 11.9 months, respectively). Conversely, recent reports suggest that the conversion of IONM to R0 resection with additional resection or even total pancreatectomy may be associated with improved survival. The discordance between these conflicting studies could be explained in part by the influence of biologic and physiologic selection on the association of IONM re-resection and survival. Since most studies did not include patients receiving modern combination chemotherapy regimens, the intersection between margin status, tumor biology, and chemoresponsiveness remains unclear. Furthermore, there are no dedicated data to guide surgical management in IONM-positive pancreaticoduodenectomy for patients receiving neoadjuvant chemotherapy. Conclusions and Relevance: Although data regarding the oncologic utility of additional resection to achieve a tumor-free margin following initial IONM positivity during pancreaticoduodenectomy for PDAC are conflicting, they suggest that IONM positivity may be a surrogate for biologic aggressiveness that is unlikely to be mitigated by the extent of surgical resection. The complex relationship between margin status and chemoresponsiveness warrants exploration in studies including patients receiving increasingly effective neoadjuvant chemotherapy.

Diabetes mellitus in intraductal papillary mucinous neoplasms: A systematic review and meta-analysis.

BACKGROUND: Our current knowledge of diabetes mellitus in intraductal papillary mucinous neoplasm is very limited and its prevalence and predictive value for malignant transformation are not clear. This study sought to systematically review the literature to define the prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm and to evaluate the association of diabetes mellitus with the progression to high-grade dysplasia or invasive cancer. METHODS: A PubMed/Medline systematic search was performed to identify studies reporting data on preoperative diabetes mellitus in intraductal papillary mucinous neoplasm. Articles meeting the predefined inclusion criteria were analyzed and a meta-analysis was performed. The study was preregistered (PROSPERO ID: CRD42020153581). RESULTS: From the initially detected 827 studies, 27 studies including resected patients with histologically confirmed intraductal papillary mucinous neoplasm were included. The global prevalence of preoperative diabetes mellitus was 25% (1,112 of 4,412); whereas new-onset/worsening diabetes mellitus was reported in 6% of patients (68 of 1,202). The meta-analysis revealed that patients with pre-existing diabetes mellitus had an increased risk of harboring a main pancreatic duct involvement (risk ratio 1.43, 95% confidence interval: 1.21-1.69, P < .001), high-grade dysplasia (risk ratio 1.27, 95% confidence interval: 1.01-1.59, P = .04), and invasive cancer (risk ratio 1.61, 95% confidence interval: 1.33-1.95, P < .001). CONCLUSION: The prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm is high, and diabetic patients demonstrate an increased risk of a more aggressive disease. Therefore, diabetes mellitus should be increasingly considered in the stratification of patients with intraductal papillary mucinous neoplasm. Further investigations to determine the mechanisms behind the association with progression should be carried out.

Natural history and optimal treatment strategy of intraductal papillary mucinous neoplasm of the pancreas: Analysis using a nomogram and Markov decision model.

BACKGROUND/PURPOSE: With the increase in detection of intraductal papillary mucinous neoplasms (IPMN), a tailored approach is needed. This study was aimed at exploring the natural history of IPMN and suggest optimal treatment based on malignancy risk using a nomogram and Markov decision model. METHODS: Patients with IPMN who underwent surveillance or surgery were included. Changes in worrisome features/high-risk stigmata and malignancy conversion rate were assessed. Life expectancy and quality-adjusted life year (QALY) were compared using a nomogram predicting malignancy. RESULTS: Overall, 2006 patients with histologically confirmed or radiologically typical IPMN were enrolled. Of these, 1773 (88.4%), 81 (4.0%), and 152 (7.6%), respectively, had branch duct (BD)-, main duct-, and mixed-type IPMN at initial diagnosis. The cumulative risk of developing worrisome feature or high-risk stigmata was 19.0% and 35.0% at 5- and 10-year follow-up, respectively. The progression of malignancy rate at 10-year follow-up was 79.9% for main and mixed IPMNs and 5.9% for BD-IPMN. Nomogram-based malignancy risk prediction is well correlated with natural history based on pathologic biopsy and shows good stratification of survival. The decision model recommends surgery to maximize survival and QALY especially in those with >35% malignancy risk. CONCLUSIONS: Compared with main duct- and mixed-type IPMN, which have a high risk of malignancy (79.9%), BD-IPMN is very indolent (5.9%). The nomogram-based decision model suggests surgery rather than surveillance for patients with a high malignancy risk. The optimal treatment strategy between surgery and surveillance should consider patients' health status, malignancy risk, and centers' experience.