Benefits of neoadjuvant treatment for pancreatic cancer with major vessel invasion has been demonstrated through randomized controlled trials; however, the optimal neoadjuvant treatment strategy remains controversial, especially for radiotherapy. Therefore, we aimed to evaluate the efficacy and safety of neoadjuvant radiotherapy followed by chemotherapy and the optimal time interval to undergo surgery after radiotherapy in (borderline) resectable pancreatic cancer.

Between 2013 and 2022, patients with (borderline) resectable pancreatic cancer with vessel contact who received 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan or gemcitabine and nanoparticle albumin-bound paclitaxel as initial treatment following surgery were included. Patients who received radiotherapy after chemotherapy and those who did not were matched using 1:1 nearest-neighbor propensity scores. Propensity scores were measured using the tumor size at initial image, duration of neoadjuvant chemotherapy, and responsiveness to neoadjuvant chemotherapy.

Of 212 patients, 166 patients were retrieved for the matched cohort. Patients who received radiotherapy had significantly better postoperative survival, local control, and R0 resection rates than those who did not. Furthermore, patients who underwent surgery within 4 weeks after completing radiotherapy had lower intraoperative blood loss and a clinically relevant postoperative pancreatic fistula rate than those who underwent surgery after more than 4 weeks.

In patients with (borderline) resectable pancreatic cancer with vessel contact who were scheduled for curative-intent surgery after neoadjuvant chemotherapy, additional radiotherapy was associated with better postoperative survival and local control. Furthermore, our findings suggested that scheduling surgery within 4 weeks following radiation therapy might enhance the perioperative outcomes.

Neoadjuvant therapy is recommended for treating resectable pancreatic ductal adenocarcinoma (PDAC); however, its appropriate use in patients with resectable PDAC remains debatable.

This study aimed to identify independent poor prognostic factors and evaluate the clinical significance of neoadjuvant therapy in patients with resectable PDAC.

We retrospectively reviewed consecutive patients diagnosed with resectable PDAC at our institute between January 2003 and December 2022. We analyzed poor prognostic factors at the time of diagnosis in patients who underwent upfront surgery using the Cox proportional hazards model for overall survival (OS). The prognostic score was calculated by adding the individual prognostic factor scores.

Overall, 359 patients were included in this study, with 308 patients undergoing upfront surgery and the remaining 51 patients receiving neoadjuvant therapy. The R0 resection rate was significantly higher in the neoadjuvant therapy group (70.6%) than in the upfront surgery group (64.0%). Multivariate analysis in the upfront surgery group revealed the following independent poor prognostic factors: tumor size ≥ 35 mm, serum albumin level ≤ .5 g/dL, neutrophil-to-lymphocyte ratio ≥ 3.5, carbohydrate antigen 19-9 level ≥ 250 U/mL, and Duke pancreatic monoclonal antigen type 2 level ≥ 750 U/mL. Among patients with prognostic scores of 0-1 (n = 263), the intention-to-treat OS did not significantly differ between the neoadjuvant therapy and upfront surgery groups. Among those patients with a prognostic score of ≥ 2 (n = 96), the neoadjuvant therapy group had significantly longer intention-to-treat OS than the upfront surgery group.

Prognostic score-based stratification can help identify patients who could benefit from neoadjuvant therapy.

Long-term survival after resection for pancreatic ductal adenocarcinoma (PDAC) is impaired by very high recurrence rates. When recurrence occurs within 6 months (early recurrence: ER) the benefit of surgery is equivalent to palliative chemotherapy in unresectable patients. Therefore, ER is a surrogate of surgical futility in PDAC.

To investigate predictive factors of ER and its impact on survival, a training and a validation cohort of prospectively collected patients who underwent surgery for resectable or borderline-resectable PDAC were analyzed in two independent Pancreas Units during the same period. Logistic regression model on the training cohort identified independent predictors of ER, used to build a prognostic risk-score then tested on the validation cohort.

Out of 176 patients in the training cohort, 21.6 % experienced ER, with significant impact on survival (OS: 9.7 months vs. 32.7 months for ER vs. late/no recurrence, respectively). At multivariable analysis, three independent risk factors for ER were identified: Ca19.9 > 100 U/mL, G3 tumors and lack of adjuvant chemotherapy. Based on such features the derived ER-score stratified three prognostic classes at incremental risk of ER (12 %, 35 % and 53 %) with different OS (31.1, 19.7 and 9.3 months, respectively, p < 0.001). The ER predictive score was then tested on a validation cohort of 242 patients, 22.3 % of whom underwent ER. Despite significant differences in tumor-related features, the score was able to discriminate among the predicted ER-risk classes (15 %, 27 % and 53 %, respectively) and forecast significantly different OS (5.8, 19 and 31.1 months, p > 0.001). The discriminative capability of the score in the two cohorts was similar (training AUC = 0.72 vs. validation AUC = 0.68, p = 0.28).

An externally validated clinical score, able to identify three prognostic classes at incremental risk of developing ER after resection of PDAC is provided. In patients at high risk of ER, prediction of surgical futility may help in decision-making.

Pancreatic cancer is a malignant tumor with poor prognosis and bad curative effect. Previous studies did not confirm the role of radiotherapy in neoadjuvant treatment of borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). By reviewing new findings reported in recent years, we conducted this study to evaluate the survival impact by comparing chemoradiotherapy (CRT) with chemotherapy alone.

PubMed, Embase, MEDLINE, Web of Science, Scopus, and Cochrane Library were searched for studies reporting median overall survival (OS) in patients with BRPC or LAPC treated with neoadjuvant treatment. Secondary outcomes included progression-free survival (PFS) or disease-free survival (DFS) or recurrence-free survival (RFS) and R0 resection rate.

A total of 18 studies were included in the meta-analysis. OS (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.64-0.91, I2 = 61.7%) and PFS/DFS/RFS (HR = 0.72, 95% CI: 0.58-0.91, I2 = 52.3%) are both favored CRT. Although R0 resection rate was increased in CRT group, significant survival benefit of radiotherapy was found in LAPC and low resection rate subgroup in stratification analysis. Regression analysis showed that only tumor resectability was associated with OS.

For patients with LAPC and who are unlikely to receive resection, neoadjuvant radiotherapy seems to improve OS and PFS/DFS/RFS.

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis. Neoadjuvant chemotherapy (NAC) is increasingly used to improve survival in patients with pancreatic cancer; however, it often results in nutritional deterioration, which may negatively impact patient outcomes. Therefore, this study aimed to assess the effect of changes in nutritional status on the long-term outcomes of patients with pancreatic cancer who underwent curative surgery after NAC.

This retrospective single-center study included 148 patients with pancreatic cancer who underwent curative surgery after NAC between 2010 and 2020. The Controlled Nutritional Status (CONUT) score was used to determine the nutritional status of the patients. Patients were categorized into worsened, maintained, and improved groups based on the changes in their CONUT scores before and after NAC. We compared differences in overall survival (OS) and disease-free survival (DFS) between the groups.

The worsened nutritional status group exhibited the shortest median OS (28 months) compared to the maintained and improved groups (39 and 66 months, respectively; p = 0.01). Additionally, the worsened group demonstrated the shortest DFS compared to the other two groups (13, 22, and 39 months, respectively; p = 0.02). Multivariate analysis identified nutritional deterioration as an independent prognostic factor for OS (hazard ratios (HR), 2.11; 95% confidence intervals (CI), 1.31-3.40; p < 0.01).

Nutritional deterioration after NAC is a significant prognostic factor of poor survival outcomes in patients with pancreatic cancer. These findings indicate that serial nutritional assessments and treatment during NAC are crucial for improving patient outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of death worldwide, and its global burden has increased significantly over the past few years. The incidence of pancreatic cancer has also increased in the United States, and most of this increase is attributed to the population's aging process in addition to the rise in the prevalence of risk factors such as obesity, diabetes, smoking, and alcohol intake. Most patients with pancreatic cancer present with advanced unresectable or metastatic disease. Only a few patients present at an early stage with localized disease, and a multidisciplinary approach is required to maximize survival and outcomes. The surgical approach is an option for localized disease, and surgery's safety and efficacy have also been improved in recent years due to the increasing use of minimally invasive surgical techniques. Moreover, systematic chemotherapy has also been used and has had a significant impact on survival. More recently, neoadjuvant therapy has been used for pancreatic cancer along with radiation therapy, optimizing survival among those patients. Targeted therapies have been introduced based on genetic testing in metastatic pancreatic cancer and have shown promising results. Moreover, immune checkpoint inhibitors and targeted agents such as PARP inhibitors and vaccines have emerged with optimal results in terms of survival. To conclude, pancreatic cancer is considered a disease with poor long-term survival; however, recent developments in pharmacotherapy have changed its treatment and have improved outcomes with improved survival. Our review summarizes ongoing therapeutic options for local and metastatic pancreatic cancer. It also summarizes new state-of-the-art therapies that have emerged or are in trials, which can change the pancreatic cancer treatment perspective.

Pancreatic cancer (PC) is a highly aggressive malignancy with poor prognosis and high mortality rate. Identifying reliable biomarkers for the early diagnosis and treatment is urgently needed. This study aims to comprehensively evaluate the diagnostic and prognostic value of DUPAN-2 in PC through a meta-analysis.

We systematically searched PubMed, Embase, and other databases for studies related to DUPAN-2 and its prognostic and diagnostic relevance in PC, covering publications up to August 2024. We used pooled hazard ratios (HRs) to evaluate the prognostic value of DUPAN-2 in PC, the summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) to assess diagnostic performance, while pooled odds ratios (ORs) analyzed associations with clinicopathological features.

A total of 22 studies involving 4765 patients were included in this meta-analysis, with 11 studies focusing on diagnostic analysis, 10 on prognostic analysis, and 3 on clinicopathological features. The diagnostic meta-analysis revealed a pooled sensitivity of 0.63 (95 % CI: 0.56-0.69), a pooled specificity of 0.98 (95 % CI: 0.95-0.99), and an AUC of 0.83 (95 % CI: 0.79-0.86). Subgroup analysis indicated that a DUPAN-2 threshold at 150 U/mL achieved the highest diagnostic performance. The prognostic meta-analysis demonstrated that elevated DUPAN-2 levels were associated with poorer OS (HR = 1.70, 95 % CI: 1.36-2.14) and PFS (HR = 1.33, 95 % CI: 1.14-1.56). Additionally, the clinicopathological features meta-analysis showed that elevated DUPAN-2 levels were associated with vascular invasion (OR = 3.48, 95 % CI: 1.26-9.59), while normalized DUPAN-2 levels were associated with higher resectability (OR = 0.57, 95 % CI: 0.36-0.90) and lower N-stage (OR = 0.39, 95 % CI: 0.24-0.63) CONCLUSION: Serum DUPAN-2 demonstrates significant potential as a biomarker for diagnosis and prognosis in patients with PC.

Evidence demonstrating overall survival benefit of neoadjuvant chemotherapy (NAC) followed by surgical resection over upfront surgical resection for resectable pancreatic ductal adenocarcinoma (PDAC) has been mixed. The time to first therapy (TTFT) variable has not been studied as a contributing factor.

A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T1 and T2 PDACs from 2010 to 2020. Cox proportional hazards model was used to evaluate the impact of NAC followed by definitive surgery compared to upfront surgery on overall survival with and without TTFT.

Total of 43,174 patients were included-9874 patients with clinical stage T1 and 33,300 patients with T2 PDACs. There were increasing trends in the NAC approach from 2.9% in 2010 to more than 25% by 2020 and decreasing trends in the upfront surgery approach from 69.34% in 2010 to 31.87% by 2020. There were significant differences in TTFT according to the treatment choice with upfront surgery group having a significantly shorter TTFT-proportion of those receiving first treatment within the first week was 24.32% in the upfront surgery compared to 4.22% in the NAC group. In the adjusted cox regression without the TTFT variable, there was a 25% higher rate of death in the upfront surgery compared to the NAC group (hazard ratio 1.25, 95% confidence interval 1.19-1.30). When the adjusted regression was performed with addition of a TTFT interaction term, there was survival disadvantage of upfront surgery approach in patients whose TTFT occurred after 1 wk, but not in those with TTFT occurring in less than 1 wk (hazard ratio 1.01, 95% confidence interval 0.86-1.17).

Our study emphasizes the importance of incorporating TTFT variable when comparing NAC versus upfront surgery approach in PDAC. Future studies comparing NAC to upfront surgery in resectable PDAC should consider incorporating the TTFT variable.

The efficacy of neoadjuvant chemoradiotherapy for resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. This study was designed to evaluate neoadjuvant chemoradiotherapy by using intensity-modulated radiotherapy (NAC-IMRT) for R-PDAC compared with upfront surgery (UpS).

Among 198 patients with R-PDAC who were indicated for resection between 2013 and 2021, 130 were included in this study after excluding patients who underwent neoadjuvant chemotherapy and did not meet the NAC-IMRT criteria (Eligible set). NAC-IMRT was planned for 58 patients, and UpS was planned for 72 patients. Additionally, in 105 patients who could undergo the planned treatment (As-treated set), the surgical, pathological, and oncological outcomes were evaluated.

In the Eligible set, median overall survival (OS) was 50.5 months with NAC-IMRT and 34.7 months with UpS and progression-free survival was 20.4 months with NAC-IMRT and 13.9 months with UpS. In the As-treated set, OS was longer in the NAC-IMRT group (66.7 months vs. 34.7 months, p = 0.007). On multivariate analysis, NAC-IMRT was identified as an independent factor for better OS (hazard ratio 0.617, 95% confidence interval 0.382-0.995, p = 0.047, in the Eligible set). The incidence of postoperative complications did not show a difference between the two groups, and NAC-IMRT suppressed local tumor invasion, including lymphatic, venous, perineural invasion, and lymph node metastases.

NAC-IMRT may offer superior survival outcomes and manageable toxicity in R-PDAC patients compared with upfront surgery. This study supports the efficacy and safety of NAC-IMRT and recommends its consideration in R-PDAC treatment protocols.

Pancreatectomy with venous resection (PVR) is nowadays considered standard. However, there is still concern about increased postoperative morbidity and impaired long-term outcome depending on the type of venous resection and reconstruction. The aim was to investigate the predictors of morbidity and long-term survival in patients undergoing PVR in a high-volume center.

All consecutive patients undergoing PVR at a single center between January 2008 and January 2019 were retrieved from a prospectively maintained database. Factors associated with postoperative complications and long-term survival were analyzed.

Of 290 patients with isolated PVRs, 188 (65 %) were performed for pancreatic ductal adenocarcinoma (PDAC). Surgical complications developed in 56 % of patients (n = 163), and 11 % (n = 36) had severe complications (Clavien-Dindo>3a). The 90-day mortality was 4.1 %. Venous thrombosis occurred in 4.8 % (n = 14), resulting in one mortality (0.3 %). No technical factors were predictive for the development of severe complications. Longer vein segments >3 cm could be resected with similar short- and long-term outcome as shorter segments. The survival of patients undergoing PVR for resectable, borderline and locally advanced PDAC was similar (median of 18, 14, and 23 months, p = 0.7). On multivariate analysis, elevated CA19-9>200 U/mL and ASA score≥3 were independent predictors of survival (p = 0.02), but not resectability at diagnosis nor type of venous reconstruction.

The type of venous resection/reconstruction does not influence outcome and should be tailored according to patients' and tumors' characteristics during PVR. The long-term survival after PVR for PDAC is influenced by tumor-and patient-related characteristics, and not technical vascular-resection associated factors.

Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.

To assess the utility of volumetric tumor enhancement on CT to predict tumor treatment response and the overall survival (OS) of patients with PDAC undergoing FOLFIRINOX-based systemic chemotherapy. Additionally, we aim to explore the performance of a novel model that incorporates relevant volumetric CT-derived parameters to the established RECIST 1.1 in predicting both treatment response and OS.

In this retrospective single-institution study, 127 patients with PDAC who received FOLFIRINOX neoadjuvant chemotherapy between December 2012 and November 2021 were included. Manual volumetric segmentation of the single largest tumor was performed on portal venous phase images. Total and enhancing tumor volumes were calculated. Response by RECIST 1.1 was compared to response by tumor volume and enhancing tumor volume on follow-up CT.

There was no association between overall survival and RECIST 1.1 (p-value = 0.284), volumetric RECIST (p-value = 0.402), and other volumetric CT variables, except for a percentage reduction in enhancing tumor volume (p-value = 0.043). Using univariate survival analysis for categorical thresholds defined by CART, the percentage change in enhancing tumor volume was associated with OS (p-value = 0.018). There was also a significant association between baseline enhancing tumor volume and OS (p-value <0.0001). Using these two categories, we defined a multivariable model associated with OS (p-value <0.0001).

Percentage reduction in enhancing tumor volume was related to OS in non-surgical PDAC patients treated with FOLFIRINOX chemotherapy and could potentially be incorporated into patient survival prediction models.

Background: This study aimed to identify the prognostic factors after pancreatectomy for borderline resectable pancreatic cancer abutting major arteries (BR-A).Methods: We retrospectively investigated relationship between preoperative and intraoperative variables and overall survival (OS) through univariate and multivariate analyses. The cut-off points of preoperative therapy duration and response rates of serum carbohydrate antigen 19-9 (CA19-9) levels after preoperative therapy were determined through a minimum P-value approach using the log-rank test for OS. Overall survival was compared among patients stratified according to the independent prognostic factors and the presence or absence of pancreatectomy.Results: After pretreatment, 17 patients underwent pancreatectomy and four patients continued chemotherapy without surgery. Multivariate analysis in 17 resected BR-A patients demonstrated decreased serum CA19-9 levels and preoperative therapy duration of ≥4 months were the independent prognostic factors [hazard ratio (HR) 0.01; P = 0.002, HR 0.13; P = 0.02]. Patients who underwent surgery with decreased serum CA19-9 levels after preoperative therapy of ≥4 months had a significantly better prognosis than those without one or both of independent prognostic factors and those who did not undergo surgery (median survival time: not estimated, 23.3 months, 10.5 months, and 10.8 months; P = 0.02, P = 0.004, and P = 0.001, respectively). Furthermore, the prognosis did not significantly differ between the patients who underwent surgery without meeting either one or both criteria and those without surgery.Conclusions: Preoperative therapy duration of ≥4 months and decreased serum CA19-9 levels are independent prognostic factors among BR-A patients.

This study aimed to generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy [TNT]) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting.

Locoregional recurrences after TNT followed by surgery treated between 2009 and 2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume contour for patients treated with TNT. Recurrence patterns were also compared with existing adjuvant guidelines to assess coverage.

A database of 474 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified 80 patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aorticodiaphragmatic junction, retropancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences.

This is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented in this study can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning.

The incidence of pancreatic cancer is increasing, and up to 55% of patients present with metastatic disease at the time of diagnosis. Many patients also develop metastatic disease following surgical resection. The impact of metastatic patterns on outcomes has not been described. A retrospective chart review was conducted of patients with pancreatic adenocarcinoma treated at a tertiary care center from 2012 to 2023. Patients who presented with metastatic disease or developed metastatic disease during their treatment course were identified. Univariate analysis was performed to identify factors associated with specific metastatic patterns. Kaplan-Meier survival curves were estimated for metastatic sites and stratified by treatment.

Of the 330 patients identified, 192 (58.2%) presented with locoregional disease and underwent curative intent surgery before developing metastases, and 138 (41.8%) presented initially with metastatic disease. Median overall survival (OS) with metastases for all patients was 6 months. For patients who underwent curative intent surgery, OS was significantly worse for those who developed peritoneal metastasis compared to patients who developed other sites of metastases (median OS 5.4 vs. 9.2 months, p = 0.0005).

The development of peritoneal metastases after surgery for pancreatic cancer is associated with worse OS compared to other sites of metastatic disease.

This study aimed to evaluate the safety, efficacy, and long-term outcomes of S-1-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC).

This retrospective study included patients with PDAC who underwent S-1-based NACRT at our institute between 2010 and 2017.

Forty patients were included in the study, including 15 (37.5%) with resectable PDAC and 25 (62.5%) with borderline-resectable PDAC. The NACRT completion and resection rates were 85.0% (n = 34) and 67.5% (n = 27), respectively. Several grade 3 adverse events were observed, including leukopenia (25.0%), anorexia (17.5%), neutropenia (10.0%), thrombocytopenia (7.5%), febrile neutropenia (2.5%), elevated aspartate aminotransferase/alanine aminotransferase (2.5%) levels, and hyponatremia (2.5%). The R0 resection rate was 70.4% (n = 19/27) in patients who underwent pancreatectomy. Grades 1, 2, and 3 according to the College of American Pathologists grading system were observed in 1 (3.7%), 12 (44.4%), and 14 (51.9%) patients, respectively. Over a median follow-up period of 32.9 months (interquartile range, 9.1-68.0), the 1-, 3-, and 5-year OS rates were 81.4%, 45.5%, and 30.3%, respectively, in the intention-to-treat analysis. In the curative-intent surgery cohort (n = 27), the 1-, 3-, and 5-year OS rates were 88.9%, 48.2%, and 37.0%, respectively.

S-1-based NACRT is safe and yields acceptable long-term outcomes for patients with resectable or borderline-resectable PDAC.

This study aimed to compare the minimally invasive pancreatoduodenectomy with venous vascular resection (MI-PDVR) and open pancreatoduodenectomy with venous vascular resection (O-PDVR) for periampullary cancer.

Data of 124 patients who underwent PDVR (45 MI-PDVR, 79 O-PDVR) between January 1, 2016, and December 31, 2023, was retrospectively reviewed.

MI-PDVR is significantly better than O-PDVR in terms of perioperative outcomes (median operation time [452.69 minutes vs. 543.91 minutes; p = 0.004], estimated blood loss [410.44 mL vs. 747.59 mL; p < 0.01], intraoperative transfusion rate [2 cases vs. 18 cases; p = 0.01], and hospital stay [18.16 days vs. 23.91 days; p = 0.008]). The complications until the discharge day showed no significant difference between the two groups (Clavien-Dindo < 3, 84.4% vs. 82.3%; Clavien-Dindo ≥ 3, 15.6% vs. 17.7%; p = 0.809). In terms of long-term oncological outcomes, there was no statistical difference in overall survival (OS, 51.55 months [95% CI: 35.95-67.14] vs. median 49.92 months [95% CI: 40.97-58.87]; p = 0.340) and disease-free survival (DFS, median 35.06 months [95% CI: 21.47-48.65] vs. median 38.77 months [95% CI: 29.80-47.75]; p = 0.585), between the two groups. Long-term oncological outcomes for subgroup analysis focusing on pancreatic ductal adenocarcinoma also showed no statistical differences in OS (40.86 months [95% CI: 34.45-47.27] vs. 48.48 months [95% CI: 38.16-58.59]; p = 0.270) and DFS (24.42 months [95% CI: 17.03-31.85] vs. 34.35 months, [95% CI: 25.44-43.27]; p = 0.740).

MI-PDVR can provide better perioperative outcomes than O-PDVR, and has similar oncological impact.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC.

The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies.

Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed.

While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions.

MicroRNAs (miRNAs) are involved in chemosensitivity through their biological activities in various malignancies, including pancreatic cancer (PC). However, single-miRNA models offer limited predictability of treatment response. We investigated whether a multiple-miRNA prediction model optimized via machine learning could improve treatment response prediction.

A total of 20 and 66 patients who underwent curative resection for PC after gemcitabine-based preoperative treatment were included in the discovery and validation cohorts, respectively. Patients were classified according to their response to preoperative treatment. In the discovery cohort, miRNA microarray and machine learning were used to identify candidate miRNAs (in peripheral plasma exosomes obtained before treatment) associated with treatment response. In the validation cohort, miRNA expression was analyzed using quantitative reverse transcription polymerase chain reaction to validate its ability to predict treatment response.

In the discovery cohort, six and three miRNAs were associated with good and poor responders, respectively. The combination of these miRNAs significantly improved predictive accuracy compared with using each single miRNA, with area under the curve (AUC) values increasing from 0.485 to 0.672 to 0.909 for good responders and from 0.475 to 0.606 to 0.788 for poor responders. In the validation cohort, improved predictive performance of the miRNA combination over single-miRNA prediction models was confirmed, with AUC values increasing from 0.461 to 0.669 to 0.777 for good responders and from 0.501 to 0.556 to 0.685 for poor responders.

Peripheral blood miRNA profiles using an optimized combination of miRNAs may provide a more advanced prediction model for preoperative treatment response in PC.

Pancreatic adenocarcinoma, increasingly diagnosed in the United States, has a disheartening initial resection rate of 15%. Neoadjuvant therapy, particularly FOLFIRINOX and gemcitabine-based regimens, is gaining favor for its potential to improve resectability rates and achieving microscopically negative margins (R0) in borderline resectable cases, marked by intricate arterial or venous involvement. Despite surgery being the sole curative approach, actual benefit of neoadjuvant therapy remains debatable. This study scrutinizes current literature on oncological outcomes post-resection of borderline resectable pancreatic cancer. A MEDLINE/PubMed search was conducted to systematically compare oncological outcomes of patients treated with either neoadjuvant therapy with intent of curative resection or an "upfront resection" approach. A total of 1293 studies were initially screened and 30 were included (n = 1714) in this analysis. All studies included data on outcomes of patients with borderline resectable pancreatic adenocarcinoma being treated with neoadjuvant therapy (n = 1387) or a resection-first approach (n = 356). Patients treated with neoadjuvant therapy underwent resection 52% of the time, achieving negative margins of 43% (n = 601). Approximately 77% of patients who received an upfront resection underwent a successful resection, with 39% achieving negative margins. Neoadjuvant therapy remains marginally efficacious in treatment of borderline resectable pancreatic adenocarcinoma, as patients undergo an operation and successful resection less often when treated with neoadjuvant therapy. Rates of curative resection are comparable, despite neoadjuvant therapy being a primary recommendation in borderline resectable cases and employed more often than upfront resection. Upfront resection may offer improved resection rates by intention-to-treat, which can provide more patients with paths to curative resection.

This study aimed to assess the prognostic value of the National Comprehensive Cancer Network (NCCN) criteria for resection following neoadjuvant therapy for patients with localized pancreatic ductal adenocarcinoma (PDAC).

This retrospective single-center study assessed 193 consecutive patients with localized PDAC (104 males and 89 females; mean age, 61.1 ± 9.4 years) who underwent neoadjuvant therapy followed by surgery between January 2010 and March 2021. Combined resectability and carbohydrate antigen (CA) 19-9 evaluation before and after neoadjuvant therapy was used to determine whether patients were eligible for resection according to the NCCN criteria. Post-surgical overall survival (OS), recurrence free survival (RFS), and pathologic results were evaluated and compared between patients considered eligible according to the NCCN criteria and those considered ineligible. Preoperative factors associated with better OS and RFS also were investigated.

Of the 193 patients, 168 (87.0 %) were eligible for resection according to the NCCN criteria. The patients eligible according to the NCCN criteria showed marginally longer OS than those considered ineligible (p = 0.056). After adjustment of variables, meeting the NCCN criteria for resection was an independent predictor of better OS (hazard ratio, 0.57; 95 % confidence interval, 0.34-0.96; p = 0.034). The two groups had similar RFS. Lower T-staging (T2 or less) and less lympho-vascular invasion and peri-neural invasion were noted in the patients who met the NCCN criteria (p ≤ 0.045).

The patients eligible for resection according to the NCCN criteria showed a trend toward longer OS and better pathologic results than the patients considered ineligible.

To validate endoscopic ultrasound-guided tissue acquisition (EUS-TA) used in conjunction with stereomicroscopic on-site evaluation (SOSE) as a preoperative diagnostic tool for resectable pancreatic cancer (R-PC) and borderline resectable PC (BR-PC).

Seventy-eight consecutive patients who underwent EUS-TA for suspected R-PC or BR-PC were enrolled. The primary endpoint was the sensitivity of EUS-TA together with SOSE based on the stereomicroscopically visible white core (SVWC) cutoff value. One or two sites were punctured by using a 22-gauge biopsy needle for EUS-TA, based on the SOSE findings.

We collected 99 specimens from 56 and 22 patients with R-PC and BR-PC, respectively. Based on the SOSE results, we performed 57 procedures with one puncture. The SVWC cutoff values were met in 73.7% and 73.1% of all specimens and in those obtained during the first puncture, respectively. The final diagnoses were malignant and benign tumors in 76 and two patients, respectively. The overall sensitivity, specificity, and accuracy of EUS-TA for the 78 lesions were 90.8%, 100%, and 91.0%, respectively. The sensitivity for malignant diagnosis based on the SVWC cutoff value were 89.5% and 90.4% for the first puncture and all specimens, respectively.

The sensitivity of EUS-TA in conjunction with SOSE for malignancy diagnosis in patients with suspected R-PC or BR-PC was 90.4%.

Chemotherapy resistance has been a great challenge in pancreatic ductal adenocarcinoma(PDAC) treatments. Current first-line chemotherapy regimens for PDAC include gemcitabine-based regimens such as AG regimen (albumin paclitaxel and gemcitabine), fluorouracil-based regiments such as FOLFIRINOX regimen ((5-fluorouracil5-FU), oxaliplatin, Irinotecan) and platinum-based regimens for patients with BRCA mutations. large amounts of work have been done on exploring the mechanism underlying resistance of gemcitabine-based and platinum-based regimens, while little research has been achieved on the mechanism of FOLFIRINOX regimens resistance. Hence, we identified Polypeptide N-Acetylgalactosaminyltransferase 5, (GALNT5) as a vital regulator and a potential therapeutic target in FOLFIRINOX regimens resistance. Colony formation assays and flow cytometry assays were performed to explore the roles of GALNT5 in cell proliferation and apoptosis in PDAC treated with FOLFIRINOX. IC50 alterations were calculated in GALNT5 knockdown and overexpressed cell lines. RNA-seq followed by GSEA (gene set enrichment analysis) was displayed to explore the potential mechanism. WB (western blotting), real-time PCR, and IF (immunofluorescence) were performed to validate relative pathways. The mouse orthotopic xenograft PDAC model was established to examine GALNT5 functions in vivo. GALNT5 was highly expressed in PDAC tissues and predicted poor prognosis in PDAC. Upregulation of GALNT5 in PDAC cells conferred FOLFIRINOX resistance on PDAC by inhibiting DNA damage. Moreover, GALNT5 interacted with MYH9, thus participating in the activation of the NOTCH pathways, resulting in hampering FOI-induced DNA damage. Functions of GALNT5 promoting FOLFIRINOX resistance were validated in vivo. In this study, we found that aberrantly overexpressed GALNT5 in PDAC took part in the activation of the NOTCH pathway by interacting with MYH9, thus inhibiting the DDR to achieve FOLFIRINOX resistance and causing poor prognosis. We identified GALNT5 as a potential therapeutic target for PDAC patients resistant to FOLFIRINOX chemotherapy.

Stereotactic body radiotherapy (SBRT) is an evolving treatment for the local management of pancreatic cancer (PC). The main purpose of this study is to report our initial experience in terms of local control (LC) and toxicity for PC patients treated with SBRT.

We conducted a retrospective review of patients treated with SBRT using abdominal compression (AC) or an end-expiratory breath-holding (EEBH) technique. The median prescribed dose was 35 Gy, delivered in five fractions. Toxicities were recorded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and survival was estimated using the Kaplan-Meier method.

From 2017 to 2023, 17 PC patients were offered SBRT. Their median age was 69 years. The median follow-up from the date of diagnosis was 22.37 months. The overall survival (OS) was 94% at 1 year and 60.9% at 2 years. The progression-free survival (PFS) was 63.1% at 6 months and 56.1% at 9 months. The median OS was 26.3 months, and the median PFS was 20.6 months. The 6-month and 1-year LC rates were 71% and 50.8%, respectively.

We are successful in implementing the SBRT program at our centre. SBRT appears to be a promising treatment option for achieving LC with limited acute toxicities.

This is a case of a 67-year-old woman diagnosed with a 35-mm pancreatic body cancer with a chief complaint of epigastric discomfort. Computed tomography demonstrated invasion of the common hepatic artery, portal vein, and stomach, and chemotherapy was initiated for locally advanced pancreatic cancer. After 9 months of chemotherapy, the tumor remained stable on imaging, and the tumor markers were within the normal range. After additional chemoradiotherapy, the patient underwent a conversion surgery, a pancreaticoduodenectomy. Magnetic resonance cholangiopancreatography (MRCP) at the time of diagnosis demonstrated main pancreatic duct (MPD) dilatation on the tail side of the tumor; however, most of the MPD signal disappeared on MRCP after chemotherapy. Surgical findings failed to identify MPD on the first pancreatic resection plane, and additional resection was conducted; however, no MPD was found. As a pancreatic duct anastomosis was not available, pancreatic reconstruction was selected for pancreaticogastric anastomosis using the invagination method. Pathologically, the pancreatic tissue on the tail side of the tumor was replaced by fibrotic tissue, and MPD could not be identified. To the best of our knowledge, this is the first case report of the disappearance of a dilated pancreatic duct on the tail side accompanied by exocrine tissue loss during preoperative treatment for pancreatic cancer.

Locally advanced pancreatic cancer (LAPC) represents a unique clinical scenario in which the tumor is considered localized but unresectable due to anatomic factors. Despite a consensus against upfront surgery, no standard approach to induction therapy exists for patients with LAPC. Extended systemic therapy has shown promise in establishing tumor response and remains the standard of care. While associated with improved local control, the timing and role of radiation therapy remain in question. Following adequate response to induction chemotherapy, a safe attempt at margin-negative resection can be considered. Special attention should be given to required vascular skeletonization and/or resection with reconstruction.

Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer.

We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection).

Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%.

A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.

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.

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.

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.

The optimal resection timing following NAT is once a patient undergoes at least 3 months of neoadjuvant chemotherapy or at least eight FOLFIRINOX cycles.

Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response (p < 0.05). ESOP was also associated with a smaller tumor size (p < 0.001), more lymph nodes (p < 0.001), a lower ypN stage (p < 0.001), better differentiation (p = 0.02), and less frequent lymphovascular invasion (p = 0.009). However, since ESOP and ESOT were primarily conducted for cases with no grossly identifiable tumor or minimal residual carcinoma in initial sections, potential bias cannot be excluded. Both ESOT and ESOP were associated with less frequent recurrence/metastasis and better DFS and OS (p < 0.05) in the overall study population. ESOP was associated with better DFS and better OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response (p < 0.05). ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors (p < 0.05). Both ESOT and ESOP were independent prognostic factors for OS according to multivariate survival analyses. Therefore, accurate pathologic evaluation using ESOP and ESOT is associated with the prognosis in PDAC patients with complete or near-complete pathologic response and ypT0/ypT1 tumor after NAT.