Surgery For Pancreatic Cancer Research Articles

BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

Periarterial and Sub-adventitial Divestment Along with Triangle Operation and RAMPS for Pancreatic Body Cancer.

Locally advanced cancers of the pancreatic body can abut or involve the celiac axis, hepatic artery, or superior mesenteric artery. Recent evidence suggests that these tumors are amenable to surgery after neoadjuvant chemotherapy (Hackert et al., Locally advanced pancreatic cancer: neoadjuvant therapy with FOLFIRINOX results in resectability in 60 % of the patients. Ann Surg 264:457-463, 2016; Rangelova et al., Surgery improves survival after neoadjuvant therapy for borderline and locally advanced pancreatic cancer: a single-institution experience. Ann Surg 273:579-86, 2021). An arterial divestment technique can be used for these cancers to get an R0 clearance, thereby avoiding morbid arterial resections (Miao et al., Arterial divestment instead of resection for locally advanced pancreatic cancer (LAPC). Pancreatology 16:S59, 2016; Habib et al., Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: surgical planning with the "halo sign" and "string sign." Surgery 169(5):1026-1031, 2021; Diener et al., Periarterial divestment in pancreatic cancer surgery. Surgery 169(5):1026-31, 2020). Two techniques are described for arterial divestment. In the periarterial divestment technique, the plane of the dissection is between the tumor and the adventitia (Habib et al., Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: surgical planning with the "halo sign" and "string sign." Surgery 169(5):1026-1031, 2021; Diener et al., Periarterial divestment in pancreatic cancer surgery. Surgery 169(5):1026-31, 2020). In sub-adventitial dissection, the plane of dissection is between the tunica adventitia and the external elastic lamina (Gao et al., Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study. Langenbecks Arch Surg 406:691-701, 2021). The TRIANGLE operation also is one of the surgical techniques to achieve R0 resection in locally advanced pancreatic cancer (Hackert et al., The TRIANGLE operation: radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single-arm observational study. HPB Oxford 19:1001-1007, 2017). This multimedia article aims to demonstrate peri-arterial and sub-adventitial divestment techniques as well as the TRIANGLE operation for a locally advanced cancer of the body of the pancreas. The video also highlights the technique of posterior radical antegrade modular pancreato-splenectomy (RAMPS) together with lymph node clearance. A 57-year-old women was detected to have pancreatic body adenocarcinoma with tumor contact of the artery and superior mesenteric artery. After neoadjuvant chemotherapy, she was planned to undergo surgical resection. The surgical technique consisted of peri-arterial and sub-adventitial divestment, the TRIANGLE operation and RAMPS (Fig. 1). The procedure was performed within 240 min and involved blood loss of 250 mL. After the procedure, pancreatic leak (POPF-B), chyle leak and diarrhea developed, which were managed conservatively. The final histopathology showed residual, viable, moderately differentiated adenocarcinoma (ypT2N1M0) with all resection margins free. The surgical technique consisting of peri-arterial and sub-adventitial divestment, the TRIANGLE operation and RAMPS helps in R0 resection of locally advanced pancreatic body cancer without any compromise in oncologic outcomes and offers an alternative surgical approach to morbid arterial resection.

Skeletal Muscle Mass Index Reduction Rate as a Prognostic Indicator for Patients Undergoing Pancreatectomy for Pancreatic Cancer.

There have been many studies on skeletal muscle depletion before surgery, and skeletal muscle depletion is a known risk factor for poor prognosis. However, reports on the association between changes in skeletal muscle mass and prognosis after surgery for pancreatic cancer are very few. The data of 137 patients who underwent pancreatectomy for pancreatic cancer between 2005 and 2022 were reviewed. Muscle areas were measured at the third lumbar vertebral level, and skeletal muscle mass index (SMI) reduction rates were calculated. Patients were divided into two groups using receiver operating characteristic (ROC) curve analysis based on the SMI reduction rate with a cutoff of 14% reduction rate. The clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) were compared between the two groups. Survival rates were analyzed both univariately and multivariately to clarify the factors associated with poor prognosis after pancreatectomy. A total of 102 patients met the inclusion criteria. SMI reduction rate ≥14% significantly correlated with advanced age and higher incidence of postoperative complications. In the multivariate Cox regression analysis, preoperative prognostic nutritional index (PNI) <40 and SMI reduction rate ≥14% were significantly associated with poor OS. Tumor size ≥3.0 cm, preoperative neutrophile-lymphocyte ratio ≥3.0, and SMI reduction rate ≥14% were significantly associated with poor RFS. The rate of skeletal muscle mass reduction after pancreatic surgery is an independent prognostic factor for survival in patients with pancreatic cancer.

Comparison of Hospital Volume and Risk-Standardized Mortality Rate as a Proxy for Hospital Quality in Complex Oncologic Hepatopancreatobiliary Surgery.

Centralization of hepatopancreatobiliary procedures to more experienced centers has been recommended but remains controversial. Hospital volume and risk-stratified mortality rates (RSMR) are metrics for interhospital comparison. We compared facility operative volume with facility RSMR as a proxy for hospital quality. Patients who underwent surgery for liver (LC), biliary tract (BTC), and pancreatic (PDAC) cancer were identified in the National Cancer Database (2004-2018). Hierarchical logistic regression was used to create facility-specific models for RSMR. Volume (high versus low) was determined by quintile. Performance (high versus low) was determined by RSMR tercile. Primary outcomes included median facility RSMR and RSMR distributions. Volume- and RSMR-based redistribution was simulated and compared for reductions in 90-day mortality. A total of 106,217 patients treated at 1282 facilities were included; 17,695 had LC, 23,075 had BTC, and 65,447 had PDAC. High-volume centers (HVC) had lower RSMR compared with medium-volume centers and low-volume centers for LC, BTC, and PDAC (all p < 0.001). High-performance centers (HPC) had lower RSMR compared with medium-performance centers and low-performance centers for LC, BTC, and PDAC (all p < 0.001). Volume-based redistribution required 16.0 patients for LC, 11.2 for BTC, and 14.9 for PDAC reassigned to 15, 22, and 20 centers, respectively, per life saved within each US census region. RSMR-based redistribution required 4.7 patients for LC, 4.2 for BTC, and 4.9 for PDAC reassigned to 316, 403, and 418 centers, respectively, per life saved within each US census region. HVC and HPC have the lowest overall and risk-standardized 90-day mortality after oncologic hepatopancreatobiliary procedures, but RSMR may outperform volume as a measure of hospital quality.

Response Evaluation Criteria in Gastrointestinal and Abdominal Cancers: Which to Use and How to Measure.

As the management of gastrointestinal malignancy has evolved, tumor response assessment has expanded from size-based assessments to those that include tumor enhancement, in addition to functional data such as those derived from PET and diffusion-weighted imaging. Accurate interpretation of tumor response therefore requires knowledge of imaging modalities used in gastrointestinal malignancy, anticancer therapies, and tumor biology. Targeted therapies such as immunotherapy pose additional considerations due to unique imaging response patterns and drug toxicity; as a consequence, immunotherapy response criteria have been developed. Some gastrointestinal malignancies require assessment with tumor-specific criteria when assessing response, often to guide clinical management (such as watchful waiting in rectal cancer or suitability for surgery in pancreatic cancer). Moreover, anatomic measurements can underestimate therapeutic response when applied to molecular-targeted therapies or locoregional therapies in hypervascular malignancies such as hepatocellular carcinoma. In these cases, responding tumors may exhibit morphologic changes including cystic degeneration, necrosis, and hemorrhage, often without significant reduction in size. Awareness of pitfalls when interpreting gastrointestinal tumor response is required to correctly interpret response assessment imaging and guide appropriate oncologic management. Data-driven image analyses such as radiomics have been investigated in a variety of gastrointestinal tumors, such as identifying those more likely to respond to therapy or recur, with the aim of delivering precision medicine. Multimedia-enhanced radiology reports can facilitate communication of gastrointestinal tumor response by automatically embedding response categories, key data, and representative images. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Healthcare utilization and expenditures among patients with venous thromboembolism following gastrointestinal cancer surgery

BackgroundWe sought to assess healthcare utilization and expenditures among patients who developed venous thromboembolism (VTE) after gastrointestinal cancer surgery. MethodsPatients who underwent surgery for esophageal, gastric, hepatic, biliary duct, pancreatic, and colorectal cancer between 2013 and 2020 were identified using the MarketScan database. Entropy balancing was performed to obtain a cohort that was well balanced relative to different clinical covariates. Generalized linear models were used to compare 1-year postdischarge costs among patients who did and did not develop a postoperative VTE. ResultsAmong 20,253 individuals in the analytical cohort (esophagus [n = 518 {2.6%}], stomach [n = 970 {4.8%}], liver [n = 608 {3.0%}], bile duct [n = 294 {1.5%}], pancreas [n = 1511 {7.5%}], colon [n = 12,222 {60.3%}], and rectum [n = 4130 {20.4%}]), 894 (4.4%) developed VTE. Overall, most patients were male (n = 10,656 [52.6%]), aged between 55 and 64 years (n = 10,372 [51.2%]), and were employed full time (n = 11,408 [56.3%]). On multivariable analysis, VTE was associated with higher inpatient (mean difference [MD], $17,547; 95% CI, $15,141-$19,952), outpatient (MD, $8769; 95% CI, $7045-$10,491), and pharmacy (MD, $2811; 95% CI, $2509-$3113) expenditures (all P < .001). Furthermore, patients who developed VTE had higher out-of-pocket costs for inpatient (MD, $159; 95% CI, $66-$253) and pharmacy (MD, $122; 95% CI, $109-$136) services (all P < .001). ConclusionAmong privately insured patients aged <65 years, VTE was associated with increased healthcare utilization and expenditures during the first year after discharge.

Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer.

Pancreatic cancer surgery triggered pronounced accumulation of NOX2+ myeloid-derived suppressor cells that inhibited NK cell function and negatively prognosticated postoperative patient survival. We propose the targeting of M-MDSC as a conceivable strategy to reduce postoperative immunosuppression in pancreatic cancer.

Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

Early and Long-Term Morbidity and Mortality Following Pancreaticoduodenectomy for Periampullary Tumors in Elderly Patients.

The growing elderly population is facing an increasing risk of cancers, consequently raising the pancreatic cancer surgery rate. This study aimed to determine whether advanced age is a risk factor for morbidity and mortality following pancreaticoduodenectomy (PD) for periampullary tumors. The present study included 90 patients who underwent PD for periampullary tumors. Patients were divided into two age-related groups, including those aged 60-74 years (n = 60) (Group 1) and those aged ≥75 years (n = 30) (Group 2). Each patient's characteristics, perioperative features, morbidity, and long-term results were evaluated retrospectively. In both univariate and multivariate logistic regression analyses, old age (≥75 years) was not a risk factor for morbidity and hospital mortality. The multivariate analysis demonstrated that male gender (p = 0.008), pancreatic duct diameter (<3 mm) (p < 0.001), and length of hospital stay (p = 0.005) were independent risk factors for pancreatic fistula post-operation and reoperation. Additionally, hospital mortality was significantly associated with reoperation (p = 0.011). The overall median survival was 27 ± 4.1 (18.8-35.1) months. Lymph node positivity (p < 0.001), neural tumor invasion (p = 0.026), and age ≥75 years (p = 0.045) were risk factors affecting the overall survival rate. Moreover, there was no statistically significant difference in terms of PD rates during the Coronavirus disease-19 (COVID-19) period among groups, and PD during this period was not related to the occurrence of pancreatic fistula. PD can be performed effectively in selected elderly patients with tolerable morbidity and mortality rates.

Neoadjuvant chemotherapy may be the best neoadjuvant therapy modality for non-metastatic pancreatic cancer: a population based study.

Currently, there are no studies showing which neoadjuvant therapy modality can provide better prognosis for patients after pancreatic cancer surgery. This study explores the optimal neoadjuvant therapy model by comparing the survival differences between patients with non-metastatic pancreatic cancer (cT1-4N0-1M0) who received neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NARCT). We retrospectively analyzed the clinical data of 723 patients with cT1-4N0-1M0 pancreatic cancer who received neoadjuvant therapy before surgery from the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), we compared the effects of NACT and NARCT on overall survival (OS) and cancer-specific survival (CSS) in patients with non-metastatic pancreatic cancer, and then performed subgroup analyze. Finally, we used univariate and multivariate Cox regression analysis to explore potential risk factors for OS and CSS in patients with non-metastatic pancreatic cancer treated with preoperative neoadjuvant therapy. Before PSM, mOS (30.0 months VS 26.0 months, P=0.122) and mCSS (30.0 months VS 26.0 months, P=0.117) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, but this was not statistically significant (P>0.05). After PSM, mOS (30.0 months VS 25.0 months, P=0.032) and mCSS (33.0 months VS 26.0 months, P=0.028) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, and this difference was statistically significant (P<0.05). Multivariate Cox regression analysis results showed that age, lymph node positivity, and NARCT were independent adverse prognostic factors for OS and CSS in patients with non-metastatic pancreatic cancer. The study results show that compared with NARCT, NACT is the best preoperative neoadjuvant therapy mode for patients with non-metastatic pancreatic cancer. This result still needs to be confirmed by more prospective randomized controlled trials.

The role of national population-based registries in pancreatic cancer surgery research.

Research and innovation are critical for advancing the multidisciplinary management of pancreatic cancer. Registry-based studies (RBSs) are a complement to randomized clinical trials (RCTs). Compared with RCTs, RBSs offer cost-effectiveness, larger sample sizes, and representation of real-world clinical practice. National population-based registries (NPBRs) aim to cover the entire national population, and studies based on NPBRs are, compared to non-NPBRs, less prone to selection bias. The last decade has witnessed a dramatic increase in NPBRs in pancreatic cancer surgery, which has undoubtedly added invaluable knowledge to the body of evidence on pancreatic cancer management. However, several methodological shortcomings may compromise the quality of registry-based studies. These include a lack of control over data collection and a lack of reporting on the quality of the source registry or database in terms of validation of coverage and data completeness and accuracy. Furthermore, there is a significant risk of double publication from the most commonly used registries as well as the inclusion of historical data that is not relevant or representative of research questions addressing current practices.

Abstract 2514: Adjuvant chemotherapy drug response-related gene detection using JASPAC01 pancreatic cancer resection cohort

Abstract Background of Purpose: Although various multidisciplinary treatments have been attempted for pancreatic cancer, sufficient improvement in prognosis has not been achieved. It is necessary to establish biomarkers that can predict the malignant potential for each patient and the therapeutic effect of chemotherapy in order to select the optimal treatment for each individual case.This study was designed as a companion study to the phase III comparative study (JASPAC 01 of gemcitabine (GEM) and S-1 therapy as adjuvant chemotherapy after pancreatectomy. Among the 22 candidate biomarker genes that have been reported to be involved in pancreatic cancer treatment prognosis, we focused on E2F transcription factor 7 (E2F7), which is associated with a significantly poor overall survival rate when highly expressed. E2F7 is one of the target proteins of p53 and has been reported to be involved in cell cycle regulation. We examined the possibility of E2F7 expression in pancreatic cancer surgery and the effect of adjuvant chemotherapy. Patients and Methods: After optimizing the E2F7 imunostaining protocol, we scored E2F7 protein expression using the slides from excised tissues from JASPAC 01 registered cases. We investigated the relationship between malignancy and treatment efficacy using the case cohort treatment allocation information, clinicopathological information, and prognosis data. Results: Immunostaining was performed on approximately 330 resected pancreatic cancer specimens from 24 facilities nationwide. Of the 311 patients for whom E2F7 protein expression could be scored, 202 patients who completed the assigned treatment were included in the analysis. In 88 cases with high E2F7 expression, no significant difference in clinicopathological factors was observed between the S-1 treatment group and the GEM treatment group, but the S-1 treatment group showed better recurrence-free survival (RFS, P=0.066) and overall survival (OS, P=0.015) were observed. On the other hand, in the 114 patients with low E2F7 expression, there was no significant difference in clinicopathological factors between the two groups (RFS, P=0.168, OS: P=0.276). High E2F7 expression in pancreatic cancer tissues may affect S-1 sensitivity, GEM resistance, or both. Conclusions: It is considered that high expression E2F7 in pancreatic cancer may affect the therapeutic efficacy of GEM and S-1, which are frequently used in adjuvant chemotherapy for pancreatic cancer. Citation Format: Yukiyasu Okamura, Tomohisa Otsu, Masamichi Hayashi, Ryo Ashida, Katsuhiko Uesaka. Adjuvant chemotherapy drug response-related gene detection using JASPAC01 pancreatic cancer resection cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2514.

Abstract 5659: Origin of synchronous or metachronous multiple pancreatic cancers

Abstract [Introduction] The majority of patients with pancreatic cancer are inoperable at the time of diagnosis and even those cases with successful tumor resection for early-stage tumors frequently had second tumors within the remaining pancreas shortly after the surgery, contributing to a poor clinical outcome. Additionally, synchronous multiple pancreatic cancers have been frequently documented. One of the long-standing issues about such synchronous and/or metachronous multiple pancreatic cancers is their clonal origins. This study is designed to elucidate the origin of multiple pancreatic cancers through an unbiased detection of somatic mutations in primary and metachronous cancers, along with adjacent precursor lesions. [Methods] Serially obtained formalin-fixed paraffin-embedded surgical specimens from 20 patients who had undergone curative surgery for an early-stage pancreatic cancer were subjected to laser microdissection for the enrichment of tumor and precancerous lesions, from which DNA was extracted and analyzed for somatic mutations using whole-exome sequencing (WES) with matched normal DNA. The investigation into the shared and private mutations across different samples aimed to unveil the clonal evolution history of these lesions. [Results] We analyzed 20 patients with multiple pancreatic cancers of 2 metachronous and synchronous, 16 metachronous, and 2 synchronous tumors. In metachronous cases, all patients exhibited margin-negative pathology for the primary cancer, with a median interval of 38.9 months (ranging from 7 to 85 months) between the initial and second surgery. In addition, a total of 20 pancreatic intraepithelial neoplasia (PanIN) from 5 of these cases were analyzed. We identified a median of 66 (range: 31-232) and 20 (14-42) somatic mutations in cancer and PanIN lesions, respectively. None of the patients have known pathogenic germline variants. All samples had one or more driver mutations. In most cases (N=19), sharing many somatic mutations, multiple tumors had a common clonal origin. In another synchronous case, the synchronous tumors shared only one mutation, suggesting that they were clonally independent tumors. By contrast, none of the mutations other than hotspot KRAS mutations were shared between precursor and cancer lesions. While multiple independent clones were observed in precancerous lesions, most of multiple cancers originated from a common ancestor. Moreover, negative pathology of the margins at the initial surgery suggested that those multiple lesions arose from distant dissemination or metastasis, rather than contiguous, intraductal invasion. [Conclusions] In conclusion, our study suggests that even in early pancreatic cancer, dissemination within the pancreas may occur, contributing to the development of synchronous and metachronous cancers. Citation Format: Tomonori Hirano, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Takayuki Anazawa, Kazuyuki Nagai, Toshihiko Masui, Sachiko Minamiguchi, Hironori Haga, Takeshi Tanaka, Atsuhiro Masuda, Yuzo Kodama, Norimitsu Uza, Hiroshi Seno, Satoru Miyano, Hiroko Tanaka, Seishi Ogawa. Origin of synchronous or metachronous multiple pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5659.

Abstract 2399: Stage-matched prognosis comparison between ypTNM and pTNM stage in pancreatic cancer

Abstract Introduction: The prognostic significance of pathological stage in pancreatic cancer is well-established. The 8th American Joint Commission on Cancer (AJCC) TNM staging introduced the ypTNM stage for neoadjuvant treatment (NAT) patients responding to the increased use of NAT. Despite this, there has been no comparative assessment of the prognosis between ypTNM and pTNM stages in pancreatic cancer. This study aimed to evaluate and compare the prognoses between ypTNM and pTNM stages in surgically resected pancreatic cancer. Method: A cohort of 586 patients who underwent pancreatic cancer surgery at a tertiary center from January 2018 to March 2022 was analyzed. Exclusions comprised those with prior pancreatectomy, suspicious liver metastasis or peritoneal seeding before NAT, those with open biopsy, R2 resection, and distant metastasis during operation, and postoperative mortalities or immediate follow-up losses. Clinicopathologic demographics underwent analysis, and a propensity score-matched (PSM) analysis (1:3) was conducted based on factors influencing overall survival (OS) in multivariate analysis. Subgroup analyses, categorized by stage, compared survival between ypTNM and pTNM stages. Results: The analysis included 541 patients, with 100 undergoing NAT (ypTNM) and 441 opting for upfront surgery (pTNM). Comparable OS was observed between ypTNM and pTNM patients (median 51.0 vs. 46.0 months, 3-year survival rate (YSR) 68.7% vs 56.3%, p = 0.094). Subgroup analysis by stages I (3YSR 76.8% vs 67.5%, p = 0.577), II (56.2% vs 53.0%, p = 0.715), and III (26.5% vs 28.7%, p = 0.596) revealed similar survival between ypTNM and pTNM. Multivariate analysis identified factors such as age &amp;gt;65 (HR 1.651, p = 0.002), CA19-9 &amp;gt;150 (HR 1.476, p = 0.010), preoperative biliary drainage (HR 1.372, p = 0.048), pathologic T2 stage (HR 2.188, p = 0.002) and T3, 4 stage (HR 3.178, p &amp;lt; 0.001) compared to T0, 1 stage, lymphovascular invasion (HR 2.087, p &amp;lt; 0.001), and adjuvant treatment (HR 0.243, p &amp;lt; 0.001) associated with OS. After PSM analysis, stages I (3YSR 76.8% vs 71.7%, p = 0.923), II (56.2% vs 46.6%, p = 0.886), and III (26.5% vs 31.4%, p = 0.856) exhibited no significant difference in OS between ypTNM and pTNM stages. Conclusions: Our study underscores comparable survival outcomes between ypTNM and pTNM stages in surgically resected pancreatic cancer, affirming the applicability of the TNM staging system after NAT. Consistent survival results, even following PSM analysis, highlight the reliability of TNM staging for guiding therapeutic decisions even in patients with NAT. Citation Format: Hyeong Seok Kim, Hochang Chae, Soo Yeun Lim, Hye Jeong Jeong, So Jeong Yoon, Sang Hyun Shin, In Woong Han, Jin Seok Heo, Hongbeom Kim. Stage-matched prognosis comparison between ypTNM and pTNM stage in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2399.

Trends Over Time in Recurrence Patterns and Survival Outcomes after Neoadjuvant Therapy and Surgery for Pancreatic Cancer.

We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival. Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018. The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6mo; 3-year rate, 7%, 10%, and 20%; P < 0.005). We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.

Robotic Pancreaticoduodenectomy with 'SMA-First Approach (Posterior and Right Medial)' and 'Triangle Operation'.

Notable improvements in pancreatic cancer surgery have been due to utilization of the superior mesenteric artery (SMA)-first approach1 and triangle operation (clearance of triangle tissue between origin of SMA and celiac artery).2 The SMA-first approach was originally defined to assess resectability before taking the irreversible surgical steps. However, in the present era, resectability is judged by the preoperative radiology, and the benefit of the SMA-first approach is by improving the R0 resection rate and reducing blood loss. The basic principle is to identify the SMA at its origin and in the distal part, to guide the plane of uncinate dissection. This video demonstrates the combination of the posterior and right medial SMA-first approach along with triangle clearance during robotic pancreaticoduodenectomy (RPD). The technique consisted of early dissection of SMA from the posterior aspect, by performing a Kocher maneuver using the 'posterior SMA-first approach'. The origin of the celiac artery, along with the SMA, was defined early in the surgery. During uncinate process dissection, the 'right/medial uncinate approach' was used to approach the SMA. 'Level 3 systematic mesopancreatic dissection' was performed along the SMA,3 culminating in the 'triangle operation'.2 RESULTS: The procedure was performed within 600min, with a blood loss of 150mL and no intraoperative or postoperative complications. The final histopathology report showed a moderately differentiated adenocarcinoma (pT2, pN2), with all resection margins free. The standardized technique of the SMA-first approach and triangle clearance during RPD is demonstrated in the video. Prospective studies should further evaluate the benefits of this procedure.

Effectiveness of Preoperative Immunonutrition in Improving Surgical Outcomes after Radical Cystectomy for Bladder Cancer: Study Protocol for a Multicentre, Open-Label, Randomised Trial (INu-RC).

Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for patients with limited-stage muscle-invasive bladder cancer. RC is associated with a complication rate of approximately 50-88%. Immunonutrition (IMN) refers to the administration of substrates, such as omega-3 fatty acids, arginine, glutamine, and nucleotides, that modulate the immune response. IMN has been associated with improved outcomes following surgery for esophagogastric, colorectal and pancreatic cancer. In this paper, we describe a study protocol for a multicentre, randomised, open-label clinical trial to evaluate the effect of IMN in patients undergoing RC for bladder cancer. A 7-day preoperative course of IMN is compared with a standard high-calorie high-protein oral nutritional supplement. The primary outcome of this study is the rate of complications (infectious, wound-related, gastrointestinal, and urinary complications) in the first 30 days after RC. Secondary outcomes include time to recovery of bowel function and postoperative mobilisation, changes in muscle strength and body weight, biochemical modifications, need for blood transfusion, length of stay, readmission rate, and mortality. The results of this study may provide new insights into the impact of IMN on postoperative outcomes after RC and may help improve IMN prescribing based on patient nutritional status parameters.

Surgery for Oligometastatic Pancreatic Cancer: Defining Biologic Resectability.

Pancreatic ductal adenocarcinoma (PDAC) is most often metastatic at diagnosis. As systemic therapy continues to improve alongside advanced surgical techniques, the focus has shifted toward defining biologic, rather than technical, resectability. Several centers have reported metastasectomy for oligometastatic PDAC, yet the indications and potential benefits remain unclear. In this review, we attempt to define oligometastatic disease in PDAC and to explore the rationale for metastasectomy. We evaluate the existing evidence for metastasectomy in liver, peritoneum, and lung individually, assessing the safety and oncologic outcomes for each. Furthermore, we explore contemporary biomarkers of biological resectability in oligometastatic PDAC, including radiographic findings, biochemical markers (such as CA 19-9 and CEA), inflammatory markers (including neutrophil-to-lymphocyte ratio, C-reactive protein, and scoring indices), and liquid biopsy techniques. With careful consideration of existing data, we explore the concept of biologic resectability in guiding patient selection for metastasectomy in PDAC.

Morphology of the Dorsal Pancreatic Artery and Its Oncological Significance in Pancreatic Cancer.

Although the dorsal pancreatic artery (DPA) is an important artery that supplies the pancreas, its morphology has not been sufficiently studied. We investigated the morphology of the DPA and the progression of pancreatic cancer along this vessel. Overall, 142 patients with pancreatic cancer who underwent surgical resection at Kanazawa University Hospital between 2004 and 2015 were enrolled. We examined the morphology of the DPA using preoperative computed tomography and cancer progression along the DPA using resected specimens. We investigated the anatomical structures surrounding the DPA through cadaveric examination. The analysis of computed tomography images revealed the presence of the DPA in 141 patients. In typical cases, the DPA divides into a head and a body branch. Histopathological examination revealed cancer progression along the DPA in 32 patients. Cancer progression along the DPA was identified as a factor associated with a poor prognosis in pancreatic head or body cancer. Cadaveric examination showed the presence of abundant nerve and lymphatic tissues along the DPA. It is important to remove the soft tissue surrounding the DPA during surgery for pancreatic head or body cancer because it may serve as an important route for cancer progression.

Perioperative factors associated with survival following surgery for pancreatic cancer – a nationwide analysis of 473 cases from Denmark.

BackgroundPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers worldwide, with an overall 5-year survival rate of only 5%. The effect of perioperative treatment factors including duration of surgery, blood transfusions as well as choice of anesthesia and analgesia techniques on overall survival (OS) following pancreatic resections for PDAC, is currently not well known. We hypothesized that these perioperative factors might be associated with OS after pancreatic resections for PDAC.MethodsThis is a retrospective study from a nationwide cohort of patients who underwent surgery for PDAC in Denmark from 2011 to 2020. Kaplan-Meier 1, 2 and 5-year survival estimates were 73%, 49% and 22%, respectively. Data were obtained by joining the national Danish Pancreatic Cancer Database (DPCD) and the Danish Anaesthesia Database (DAD). Associations between the primary endpoint (OS) and perioperative factors including duration of surgery, type of anesthesia (intravenous, inhalation or mixed), use of epidural analgesia and perioperative blood transfusions were assessed using Hazard Ratios (HRs). These were calculated by Cox regression, controlling for relevant confounders identified through an assessment of the current literature. These included demographics, comorbidities, perioperative information, pre and postoperative chemotherapy, tumor staging and free resection margins.ResultsOverall, data from 473 resected PDAC patients were available. Multivariate Cox regression indicated that perioperative blood transfusions were associated with shorter OS (HR 2.53, p = 0.005), with survival estimates of 8.8% in transfused vs. 28.0% in non-transfused patients at 72 months after surgery. No statistically significant associations were identified for the duration of surgery or anesthesia/analgesia techniques.ConclusionIn this study, the use of perioperative blood transfusions was associated with shorter OS.