Development of a Fit-For-Purpose Multi-Marker Panel for Early Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

Diagnostic Performance of Surgical Indication for Branch-duct or Mixed-type Intraductal Papillary Mucinous Neoplasms of the Revised International Association of Pancreatology (IAP) 2023 Guidelines.

OBJECTIVE: To evaluate the diagnostic performance of surgical indications of the revised International Association of Pancreatology (IAP) 2023 guidelines compared to the IAP 2017 and European 2018 guidelines. SUMMARY BACKGROUND DATA: The revised IAP guidelines for surgical indications for branch duct (BD) intraductal papillary mucinous neoplasms (IPMN) include the presence of at least two worrisome features without mandatory endoscopic ultrasound. METHODS: Among 663 patients who underwent resection for pathologically confirmed IPMN in a tertiary hospital between 2013 and 2023, 556 patients with BD or mixed-type IPMN were retrospectively reviewed. Diagnostic performances of the three guidelines for predicting high-grade dysplasia or IPMN with invasive carcinoma were compared. The primary outcome was the malignancy rate. Clinicopathological and radiological imaging data were analyzed. RESULTS: A total of 540, 451, and 490 patients met the surgical indications of the IAP, 2017, 2023, and European guidelines, respectively. Malignant IPMN was observed in 229 (41.2%) patients (high-grade dysplasia, n=99; invasive carcinoma, n=130). Surgical indication by the IAP 2023 guidelines showed higher specificity (29.1 vs. 4.9%, P<0.001), positive predictive value (48.6 vs. 42.4%, P=0.031), and accuracy (55.5 vs. 44.1%, P<0.001) than the IAP 2017 guidelines. It also had higher specificity than the European guidelines (18.7%, P=0.024). The IAP 2023 guidelines showed a superior AUC of surgical indication (0.623 vs. 0.582 for the European guidelines, P<0.001; and 0.524 for the IAP guidelines, P=0.008). CONCLUSIONS: The IAP 2023 guidelines showed better malignancy prediction than the IAP 2017 and European guidelines, potentially reducing unnecessary surgeries.

In Neoadjuvant FOLFIRINOX Chemotherapy for Pancreatic Ductal Adenocarcinoma, Which Response is the More Reliable Indicator for Prognosis, Radiologic or Biochemical?

BACKGROUND: In this era of increasing neoadjuvant chemotherapy, methods for evaluating responses to neoadjuvant chemotherapy are still diverse among institutions. Additionally, the efficacy of adjuvant chemotherapy for patients undergoing neoadjuvant chemotherapy remains unclear. Therefore, this retrospective study was performed to evaluate the effectiveness of methods for assessing response to neoadjuvant chemotherapy and the need for adjuvant chemotherapy in treating patients with non-metastatic pancreatic ductal adenocarcinoma. METHODS: The study identified 150 patients who underwent neoadjuvant FOLFIRINOX chemotherapy followed by curative-intent pancreatectomy. The patients were stratified by biochemical response based on the normalization of carbohydrate antigen 19-9 and by radiologic response based on size change at imaging. RESULTS: The patients were classified into the following three groups based on their response to neoadjuvant chemotherapy and prognosis: biochemical responders (BR+), radiology-only responders (BR-/RR+), and non-responders (BR-/RR-). The 3-year overall survival rate was higher for BR+ (71.0%) than for BR-/RR+ (53.6%) or BR-/RR- (33.1%) (P < 0.001). Response to neoadjuvant chemotherapy also was identified as a significant risk factor for recurrence in a comparison between BR-/RR+ and BR+ (hazard ratio [HR], 2.15; 95% confidence interval [CI] 1.19-3.88; P = 0.011) and BR-/RR- (HR, 3.82; 95% CI 2.41-6.08; P < 0.001). Additionally, regardless of the response to neoadjuvant chemotherapy, patients who completed adjuvant chemotherapy had a significantly higher 3-year overall survival rate than those who did not. CONCLUSIONS: This response evaluation criterion for neoadjuvant chemotherapy is feasible and can significantly predict prognosis. Additionally, completion of adjuvant chemotherapy could be helpful to patients who undergo neoadjuvant chemotherapy regardless of their response to neoadjuvant chemotherapy.

Long-Term Outcome of Proximal Gastrectomy for Upper-Third Advanced Gastric and Siewert Type II Esophagogastric Junction Cancer Compared With Total Gastrectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.

Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer.

BACKGROUND: Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. METHODS: In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. RESULTS: Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77-1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. CONCLUSIONS: We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.

Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature. METHODS: This review was guided by PRISMA. Research questions were framed in PICO format "CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?". PubMed was searched from January-April 2022. RESULTS: The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0-2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice. CONCLUSIONS: For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.

Inadequacy of the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system for invasive carcinoma associated with premalignant lesions in the pancreas: an analysis using the National Cancer Database.

BACKGROUND: Invasive carcinomas arising from premalignant lesions are currently staged by the same criteria as conventional pancreatic ductal adenocarcinoma. METHODS: Clinicopathologic information and survival data were extracted through a thorough search of histology codes from National Cancer Database (2006-2016). A total of 723 patients with invasive intraductal papillary mucinous neoplasm and mucinous cystic neoplasm were analyzed. RESULTS: The median age was 67 years, and 351 patients (48.5%) were male. There were 212 (29.3%), 232 (32.1%), 272 (37.6%), and 7 (1.0%) patients with T1, T2, T3, and T4 classification. Extrapancreatic extension (EPE) was present in 284 (39.3%). Age (HR = 1.504, 95% CI 1.196-1.891), R1 or R2 resection (HR = 1.585, 95% CI 1.175-2.140), and EPE (HR = 1.598, 95% CI 1.209-2.113) were independent prognostic factors for overall survival. Size criteria did not significantly affect survival. The median survival was 115.9 months for patients without EPE, compared to 34.2 months for those with EPE. EPE discriminated survival better than tumor size. DISCUSSION: The T classification of the eighth edition AJCC staging system is not adequate for invasive carcinomas associated with premalignant lesions of the pancreas. They merit a separate, dedicated staging system that uses appropriate prognostic factors.

Oncologic safety of robotic extended cholecystectomy for gallbladder cancer.

BACKGROUND: Although laparoscopic cholecystectomy is applicable for the treatment of early gallbladder cancer (GBC), minimally invasive surgery is not widely used for advanced GBC. This is because advanced GBCs necessitate complicated surgical techniques, including lymph node dissection and liver resection. Robotic extended cholecystectomy (REC) is thought to overcome the limitations of laparoscopic surgery, but oncological safety studies are lacking. Therefore, in this study, we aimed to evaluate the oncologic outcomes of REC compared with those of open extended cholecystectomy (OEC). METHODS: A total of 125 patients, who underwent extended cholecystectomy for GBC with tentative T2 or higher stage between 2018 and 2021, were included and stratified by surgical methods. To minimize the confounding factors, 1:1 propensity-score matching was performed between the patients who underwent REC and those who underwent OEC. RESULTS: Regarding short-term outcomes, the REC group showed significantly lower estimated blood loss (382.7 vs. 717.2 mL, P = 0.020) and shorter hospital stay (6.9 vs. 8.5 days, P = 0.042) than the OEC group. In addition, the REC group had significantly lower subjective pain scores than the OEC group from the day of surgery through the 5th postoperative day (P = 0.006). Regarding long-term outcomes, there were no significant differences in the 3-year [5-year] overall survival (OS) and disease-free survival (DFS) rates between the REC group [OS, 92.3% (92.3%); DFS, 84.6% (72.5%)] and the OEC group [OS, 96.8% (96.8%); DFS, 78.2% (78.2%)] (P = 0.807 for OS and 0.991 for DFS). CONCLUSIONS: In this study, REC showed superior short-term outcomes to OEC and no difference in long-term survival outcomes. Additionally, REC was superior to OEC in terms of postoperative pain. Therefore, REC may be a feasible option with early recovery compared with OEC for patients with advanced GBC.

Parallel Analysis of Pre- and Postoperative Circulating Tumor DNA and Matched Tumor Tissues in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for early tumor detection and minimal residual disease (MRD) assessment in early-stage cancer, but quantifying minute amounts of ctDNA is challenging and well-designed studies on ctDNA in early-stage cancer are still lacking. Here, we adapted a sensitive next-generation sequencing (NGS) technology and performed parallel analysis of pre- and postoperative ctDNA and matched tumor tissues in a prospective cohort of patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: In total, 70 consecutive patients undergoing curative resection for resectable PDAC were enrolled. We performed integrated digital error suppression-enhanced cancer personalized profiling by deep sequencing NGS of triple-matched samples (pre/postoperative plasma cell-free DNA [cfDNA], tumor tissue, and genomic DNA) targeting 77 genes. RESULTS: Preoperative ctDNA was detected in 37.7% of the evaluable patients, with a median variant allele frequency of 0.09%. Twelve additional oncogenic mutations were detected exclusively in preoperative ctDNA but not in tissue. When quantitative concentrations of ctDNA were estimated in haploid genome equivalents per milliliter (hGE/mL), the risk of early recurrence was high in patients with postoperative ctDNA >1 hGE/mL. cfDNA variants from 24.5% of patients had features compatible with clonal hematopoiesis. CONCLUSIONS: An optimized NGS approach might add value beyond tissue analysis through the highly sensitive detection of minute amounts of ctDNA in resectable PDAC. Postoperative ctDNA concentration could be a tool for MRD assessment. Moreover, parallel analyses of matched tissues and leukocytes might be required to accurately detect clinically relevant ctDNA.

Oncological outcome of proximal and middle extrahepatic bile duct cancer according to surgical extent (Is hilar resection oncologically acceptable in proximal and middle extrahepatic bile duct cancer?).

BACKGROUND: For proximal to middle bile duct cancer, it is controversial whether bile duct resection alone is sufficient, or whether hepatic or pancreatic resection should be accompanied by initial planning. This study aimed to determine the optimal surgical extent based on oncological outcomes in patients with proximal to middle bile duct cancer. METHODS: Patients who underwent surgery for proximal to middle extrahepatic bile duct cancer, hilar resection, or combined resection of other organs were included. Clinicopathological characteristics and survival analyses were compared according to operation type. RESULTS: Among 156 patients in total, R0 rate was 56.7% for hilar resection and 82.7% for other organ resection. Although hilar resection was associated with shorter hospital stay and fewer overall complications, operation type did not affect overall survival (p = 0.259) and disease-free-survival (p = 0.774). Overall survival differed according to R status (5YSR 49.8 vs. 27.1%; p = 0.012). CONCLUSION: In proximal to middle extrahepatic bile duct cancer, surgery should be tailored to achieve R0 resection according to the extent of the disease rather than uniformly resecting extensively with other organ resections. Hilar resection could be selected if R0 resection is feasible, considering the lower morbidity with similar long-term survival.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. METHODS: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. RESULTS: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). CONCLUSIONS: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Efficacy of local treatment for isolated liver metastasis after pancreatectomy in pancreatic ductal adenocarcinoma: A propensity score-matched analysis.

BACKGROUND: Although attempts of local treatment for isolated liver recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) have increased, the efficacy remains unclear. Therefore, we aimed to evaluate the effect of local treatment for recurrent liver lesions after pancreatectomy on the survival of patients with PDAC. METHODS: Patients who were diagnosed with isolated liver recurrence after pancreatectomy at a high-volume center were included. We classified these patients based on the treatment options after recurrence and performed propensity score matching to minimize confounding. RESULTS: Median with interquartile range survival after recurrence was significantly longer for patients who underwent local treatment for recurrent liver lesions plus chemotherapy (22.0 [17.0-29.0] months) than those treated with chemotherapy alone (13.0 [7.0-21.0] months, p = .027). In multivariate analysis, not only local treatment for recurrent liver lesions plus chemotherapy (hazard ratio [95% confidence interval], 0.55 [0.32-0.94]; p = .030) but also indicators for systemically controlled tumor such as late recurrence (0.57 [0.35-0.92]; p = .021), chemotherapy for ≥6 months (0.25 [0.15-0.42]; p < .001), and disease control by chemotherapy (0.36 [0.22-0.60]; p < .001) were identified as favorable prognostic factors. CONCLUSIONS: PDAC patients with stable recurrent liver lesions should be considered a candidate for local treatment.

Re-evaluation of risk and oncological outcomes of resection of veins and arteries in the resection of pancreatic cancer.

BACKGROUND: Advances in chemotherapy have led to increasing major vascular resection during pancreatectomy which has been contraindicated due to high morbidity. This study aimed to verify the safety and oncological outcomes of vascular resection during pancreatectomy in the era of neoadjuvant therapy. METHODS: Data from patients who underwent surgery for pancreatic cancer at Seoul National University Hospital between 2001 and 2021 were reviewed. Clinicopathological outcomes were analyzed according vessel resection. A propensity-score-matched (PSM) analysis was performed to evaluate survival outcomes. RESULTS: Of 1596 patients, the proportion of those who underwent vascular resection increased from 9.2% to 23.4% over time divided into 5-year intervals. There were no differences in major complications (15.6% vs. 13.0%; p = .266) and 30-day mortality rate (0.3% vs. 0.6%; p = .837) between the vascular and nonvascular resection groups. After PSM, the vascular resection group demonstrated comparable survival outcome with the nonvascular resection group (5 year-survival-rate 20.4 vs. 23.7%; p = .194). Arterial resection yielded comparable survival outcome with nonvascular resection (5 year-survival-rate 38.1% vs. 23.7%; p = .138). CONCLUSIONS: Appropriate vascular resection-even arterial-is safe and effective in patients carefully selected for radical surgery in the era of neoadjuvant therapy. Further studies are needed to determine the optimal indication and method for vascular resection in patients with pancreatic cancer.

Clinical outcomes of preservation versus resection of portal/superior mesenteric vein during pancreaticoduodenectomy in pancreatic cancer patients who respond to neoadjuvant treatment: A retrospective cohort study.

BACKGROUND: R0 rates have increased as neoadjuvant treatment (NAT) has become the primary treatment for pancreatic ductal adenocarcinoma (PDAC) with venous involvement, suggesting a decrease in venous tumor infiltration. The aim of this study was to investigate the clinical outcomes of preserving the portal/superior mesenteric vein (PV/SMV) during pancreaticoduodenectomy (PD) in PDAC patients who underwent NAT. MATERIAL AND METHODS: The 113 patients with resectable and borderline resectable PDAC with venous involvement who responded to NAT and underwent curative PD between 2012 and 2022 were retrospectively reviewed. RESULTS: Among the 113 patients, PV/SMV preservation (PVP) was performed in 68 patients (60.2%), and PV/SMV resection (PVR) was performed in 45 patients (39.8%). There was no significant difference in the R0 rate, 5-year overall survival (OS) and recurrence-free survival between the two groups. PV/SMV stenosis within 3 months after surgery was more common in the PVR group than in the PVP group (1.5% versus 22.2%; P < 0.001), and 5-year PV/SMV stenosis-free survival was significantly higher in the PVP group than in the PVR group (76.5% versus 53.4%; P=0.014). Multivariate analysis showed that gemcitabine-based neoadjuvant chemotherapy was associated with poor OS. PVR, clinically relevant postoperative pancreatic fistula, and locoregional recurrence were independent risk factors for PV/SMV stenosis. CONCLUSION: The PVP group had similar oncologic outcomes and better vessel-functional outcomes than the PVR group. Therefore, if dissection is possible and there is a high likelihood of achieving R0 resection after NAT, routine PVR may be unnecessary in PDAC patients with venous involvement.

Examining neoadjuvant treatment candidates in resectable pancreatic cancer based on tumor-vessel interactions and CA 19-9 levels: a retrospective cohort study.

INTRODUCTION: The applicability of neoadjuvant treatment (NAT) for resectable pancreatic ductal adenocarcinoma (PDAC) has arisen, however, high-level evidence is lacking. This study aimed to explore patient subgroups with high-risk resectable PDAC for selecting candidates who may benefit from NAT. METHODS: The 1132 patients with resectable or borderline resectable PDAC who underwent surgery between 2007 and 2021 were retrospectively reviewed. Patients with resectable PDAC without contact of major vessels (R-no contact) ( n =651), with contact of portal vein or superior mesenteric vein (PV/SMV) ≤180° (R-contact) ( n =306), and borderline resectable PDAC without arterial involvement (BR-V) ( n =175) were analyzed. RESULTS: The mean age was 64.3±9.8 years, and 647 patients (57.2%) were male. The median follow-up was 26 months in the entire cohort. Patients with resectable PDAC without vascular contact had the most improved overall survival (OS) (median; 31.5 months). OS did not significantly differ between NAT and upfront surgery in the entire resectable PDAC cohort. However, in R-contact group, NAT showed significantly improved OS compared to upfront surgery (33 vs. 23 months). Neoadjuvant FOLFIRINOX was showed a better OS than gemcitabine-based regimens in patients who underwent NAT (34 vs. 24 months). NAT was associated with a better survival in the patients with CA 19-9 level ≥150 U/ml, only when the tumor has PV/SMV contact in resectable disease (40 vs. 19 months, P =0.001). CONCLUSIONS: NAT can be considered as an effective treatment in patients with resectable PDAC, particularly when the tumor is in contact with PV/SMV and CA 19-9 ≥150 U/ml.

Optimal timing of surgery after neoadjuvant treatment in borderline resectable pancreatic cancer.

BACKGROUND: Neoadjuvant treatment (NAT) is standard for borderline resectable pancreatic cancer (BRPC). However, consensus is lacking on the optimal surgical timing for patients with BRPC undergoing NAT. The aim of this study was to investigate the long-term outcomes of patients undergoing NAT for BRPC and suggest optimal resection timing. METHODS: Prospectively collected data for 282 patients with BRPC between January 2007 and December 2019 were retrospectively reviewed. There were 164 patients who underwent NAT followed by surgery, 45 for chemotherapy only, and 73 for upfront surgery. Among them, 150 patients who underwent R0 or R1 resection following NAT were investigated to identify prognostic factors. RESULTS: Patients receiving NAT followed by surgery showed the best survival (median overall survival [OS]; NAT followed by surgery vs. upfront surgery vs. chemotherapy only; 35 vs. 23 vs. 16 months). In the NAT group, 54 (36.0%) patients received less than 3 months of NAT, 68 (45.3%) received ≥3, <6 months, and 28 (18.7%) received longer than 6 months. Patients receiving ≥3 months of NAT showed an improved OS compared to <3 months (median; not reached vs. 27 months). In the FOLFIRINOX group, patients who received more than eight FOLFIRINOX cycles showed a good prognosis (<6 vs. 6-7 vs. ≥8 cycles; median survival, 26 vs. 41 months vs. not-reached). However, >12 cycles did not carry a survival benefit compared to 8-11 cycles. CONCLUSION: The optimal resection timing following NAT is once a patient undergoes at least 3 months of neoadjuvant chemotherapy or at least eight FOLFIRINOX cycles.

Prospective Comparison of [18F]FDG and [18F]AIF-FAPI-74 PET/CT in the Evaluation of Potentially Resectable Pancreatic Ductal Adenocarcinoma.

PURPOSE: Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [18F]FDG and [18F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC. PROCEDURES: Between 2021 and 2022, twenty participants with newly diagnosed potentially resectable PDAC were enrolled. After the initial evaluation with pancreatic CT, [18F]FDG PET/CT, and [18F]AIF-FAPI-74 PET/CT, treatment strategies were determined considering the participant's general status, clinical staging, and resectability. Pathological information from the surgical specimens was only available in 17 participants who underwent curative-intent surgery. Head-to-head comparisons of quantitative radiotracer uptake and diagnostic performance were performed among imaging modalities. RESULTS: [18F]AIF-FAPI-74 PET/CT showed a significantly higher maximum standardized uptake value than [18F]FDG PET/CT did in evaluating primary pancreatic lesions (median [interquartile range]; 12.6 [10.7-13.7] vs. 6.3 [4.8-9.2]; P < 0.001). In contrast, [18F]AIF-FAPI-74 PET/CT showed a significantly lower mean standardized uptake value than [18F]FDG PET/CT did in evaluating background organ (median [interquartile range]) 0.8 [0.7-0.9] vs. 2.6 [2.3-2.7]; P < 0.001). In addition, the sensitivity of [18F]AIF-FAPI-74 PET/CT in detecting metastatic lymph nodes was higher than that of [18F]FDG PET/CT (50.0% vs. 0.0%; P = 0.026). CONCLUSION: This study demonstrated that [18F]AIF-FAPI-74 PET/CT could improve the clinical staging of potentially resectable PDAC.

Optimal Surveillance Interval of Branch Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Importance: Despite the increasing prevalence of intraductal papillary mucinous neoplasm (IPMN), data on the growth and malignant conversion rates based on long-term surveillance cohorts are limited. Many international guidelines recommend surveillance for benign lesions, but the optimal interval and duration are unclear. Objective: To determine the optimal surveillance protocol for IPMN and propose which patients may be exempted from surveillance. Design, Setting, and Participants: This large-scale, international cohort study examined data of 3825 patients with IPMN treated at 5 tertiary pancreatic centers. Included were patients with branch duct (BD) IPMN who underwent surveillance or surgery between January 1, 1988, and December 31, 2020. After a thorough review, 3656 patients were included in the analytic sample. Changes in cyst size, worrisome features or high-risk stigmata, and malignant conversion rates were assessed. Patients who underwent surveillance over 5 years were compared to suggest discontinuation of surveillance protocol. Clinical data collection began in January 1, 2021, and the mean (SD) follow-up duration was 84 (47.7) months. The data analysis was performed from May 2, 2022, through September 14, 2022. Exposure: The patients with BD-IPMN were followed up based on International Association of Pancreatology guidelines. Patients with suspicious malignant neoplasms during surveillance underwent surgical resection. Main Outcome and Measures: The main outcome of this study was the optimal follow-up interval and duration of BD-IPMN surveillance. The association among cyst size, growth rate, and progression was examined using descriptive statistics. Results: Of the 3656 patients with BD-IPMN in the analytic sample (1973 [54.0%] female; mean [SD] age, 63.7 [10.2] years), 172 (4.7%) were confirmed to have malignant lesions through surgery. Considering cyst growth, the time to develop worrisome features, and malignant conversion, a 1.5-, 1-, and 0.5-year surveillance interval could be optimal for cysts smaller than 20 mm, 20 to 30 mm, and 30 mm, respectively, after initial short-term (6-month) follow-up. Patients with cysts smaller than 20 mm, no worrisome features, and no growth during 5-year surveillance did not show malignant conversion after 5 years of follow-up and had time to progression of greater than 10 years. Conclusions: These findings suggest that BD-IPMN surveillance may depend on the size of the cyst and morphologic changes at the initial 6-month follow-up. For patients with small cysts (ie, <20 mm) with no morphologic changes during the initial 5-year surveillance period, surveillance may be discontinued for those unfit for surgery or who have a limited life expectancy of 10 years or less.

The role of local treatment including pancreatectomy for pancreatic ductal adenocarcinoma patients with isolated synchronous liver metastasis: Propensity score-matched analyses.

BACKGROUND: In an era of more effective chemotherapy for pancreatic ductal adenocarcinoma (PDAC), the paradigm of local treatment is changing. However, the efficacy of local treatment in patients with isolated liver metastasis remains unclear. Therefore, we aimed to evaluate the effectiveness of pancreatectomy ± local treatment for metastasis (cytoreductive surgery) in PDAC patients with isolated synchronous liver metastasis. METHODS: In total, 239 patients with isolated liver metastasis were extracted from Seoul National University Hospital (SNUH). For comparison, another 12 637 patients were extracted from the National Cancer Database (NCDB). Propensity score matching was performed to minimize confounding in both cohorts. Survival analyses stratified by the treatment delivered were performed using Kaplan-Meier estimates and log-rank tests. RESULTS: In the SNUH cohort, the median (interquartile range) survival was 20.5 (13.0-42.0) months for patients who underwent cytoreductive surgery plus chemotherapy versus 12.0 (10.0-18.0) months for those who received chemotherapy alone (P < .001). With the NCDB cohort, the median (interquartile range) survival was 15.6 (8.9-31.2) months for patients who underwent cytoreductive surgery plus chemotherapy versus 7.4 (3.4-13.2) months for those who received chemotherapy alone (P < .001). CONCLUSION: Patients with isolated synchronous liver metastasis should be considered for cytoreductive surgery in addition to effective chemotherapy.