Survival and surgical benefits of neoadjuvant treatments (NAT) in resectable pancreatic cancer (RPC) remains unclear. The role of NAT in providing additional benefits to reduce biological aggressiveness and recurrence is worth elucidating. We assessed the latest randomized controlled trials (RCTs).

A systematic review and meta-analysis was performed including trials published from inception to February 2024 to evaluate survival, surgical, and short-term oncological benefits with RCTs for RPC, comparing NAT with upfront surgery.

Eight RCTs with 982 patients were analyzed. RPC treated with NAT conferred better median disease-free survival (DFS) compared to upfront surgery (HR = 0.66, p = 0.01) with a significantly improved R0 resection (RR = 1.20, p = 0.04) and pN0 rate (RR = 1.68, p < 0.001). These benefits did not translate into overall survival benefits (HR = 0.81, p = 0.06). Postoperative major morbidity and mortality did not differ significantly between treatment approaches. No significant difference was noted in resection rate (RR = 0.95, p = 0.21). However, a significantly lower surgical exploration rate was exhibited in the NAT group (RR = 0.84, p = 0.007).

NAT conferred better DFS with significantly improved R0 resection rate and pN0 rate compared with upfront surgery. Our findings highlight the potential benefits of NAT in enhancing survival, surgical, and short-term oncological outcomes without increasing postoperative risks.

Pancreatic cancer comes with one of the poorest prognoses of all cancers and as such it is crucial that new therapies are developed to improve on the current statistics. Currently, chemotherapy is the cornerstone of pancreatic cancer treatment with several drugs, and combinations of drugs being utilised for their anti-cancer effect. However, pancreatic cancer has a dense stroma around the tumour and intratumoral bacteria which result in drugs having difficulty penetrating the tumour or being metabolised by bacteria rendering them inactive. The utilisation of nanotechnology in chemotherapy for pancreatic cancer has been a huge area of focus for researchers worldwide with most of the focus being on lipid-based, inorganic and polymer-based nanoparticles. Solid lipid nanoparticles which have been studied since being first published in the 1990s, have been poorly researched for pancreatic cancer applications. Being composed of physiological lipids, solid lipid nanoparticles offer a greatly reduced risk of acute or chronic toxicities arising compared to inorganic or polymeric nanoparticles. They also possess the ability to improve on circulation time, permeability, and bioavailability of many first-line chemotherapeutics.

Despite limited RCTs, neoadjuvant chemotherapy (NAC) shows promise for resectable pancreatic adenocarcinoma (rPAC). Few prospective results are available on completing the full therapeutic sequence and oncologic outcomes with NAC.

The PANACHE01-PRODIGE48 phase II trial randomly assigned 153 patients with rPAC (2:2:1) to four cycles of NAC (modified leucovorin, fluorouracil, irinotecan, and oxaliplatin [mFOLFIRINOX], arm 1; leucovorin, fluorouracil, and oxaliplatin [FOLFOX], arm 2) or up-front surgery (control) across 28 French centers (February 2017-July 2020). The primary objective was to evaluate the feasibility and efficacy of these NAC regimens. Two binary primary end points included 1-year overall survival (OS) postrandomization and the rate of patients completing the full therapeutic sequence. Event-free survival (EFS) assessed time to failure, defined as progression before surgery, unresectable/metastatic disease at surgery, recurrence, or death.

The primary objective was achieved for arm 1. In the intention-to-treat population, 70.8% (90% CI, 60.8 to 79.6) and 68% (90% CI, 55.5 to 78.8) completed the therapeutic sequence in arm 1 and arm 2, respectively. Within 12 months postrandomization, 84.3% (90% CI, 75.3 to 90.9) and 71.4% (90% CI, 59.0 to 81.8) of the patients were alive in arm 1 and arm 2, respectively. Treatment was safe and well-tolerated in both NAC arms. Arm 2 was stopped after interim analysis for lack of efficacy (H0 rejection for 1-year OS). One-year EFS rates were 51.4% (95% CI, 41.0 to 64.3), 43.1% (95% CI, 31.3 to 59.5), and 38.7% (95% CI, 24.1 to 62.0) in arm 1, arm 2, and control arm, respectively.

The feasibility and efficacy of mFOLFIRINOX in the perioperative setting are confirmed concerning therapeutic sequence completion and oncologic outcomes, supporting ongoing trials (PREOPANC3, Alliance AO21806). Further research is needed to identify patients who benefit from NAC (ClinicalTrials.gov identifier: NCT02959879; EudraCT: 2015-001851-65).

Background: Pancreatoduodenectomy with venous resection (PDVR) may be performed to achieve tumour clearance in patients with a pancreatic ductal adenocarcinoma (PDAC) with venous involvement. This study aimed to evaluate the impact of PDVR on PDAC outcomes. Methods: In total, 435 PDAC patients with either R0 status (n = 322) or R1 status within the superior mesenteric vein groove (n = 113) were extracted from the Recurrence After Whipple's (RAW) study dataset. PDVR patients were matched in a 1:2 ratio with standard PD patients. Comparisons were then made between the two groups (surgical radicality and survival). Results: A total of 81 PDVRs were matched with 162 PDs. Neoadjuvant chemotherapy (5.7% vs. 13.6%, p = 0.032) and R1 resection rates (17.9% vs. 42%, p < 0.001) were higher in the PDVR group. Risk factors for R1 resection included venous resection (p < 0.001 for sleeve and p = 0.034 for segmental resection), pT3 (p = 0.007), and pN1 stage (p = 0.045). PDVR patients had lower median overall survival (OS, 21 vs. 30 months (m), p = 0.023) and disease-free survival (DFS, 17 m vs. 24 m, p = 0.043). Among PDVR patients, R status did not impact on OS (R0: 23 m, R1: 21 m, p = 0.928) or DFS (R0: 18 m, R1: 17 m, p = 0.558). Irrespective of R status, systemic recurrence was higher in the PDVR group (p = 0.034). Conclusions: Independent of R status, the PDVR group had lower overall survival and higher systemic recurrence rates.

Covered self-expandable metallic stents (CSEMS) are effective for managing malignant distal biliary obstruction (MDBO). However, migration is a significant problem, which requires prevention. The novel multi-hole fully CSEMS (MHSEMS), which features multiple small holes on the covered membrane, is expected to prevent migration. This study aimed to evaluate the efficacy and safety of MHSEMS for MDBO.

This multicenter retrospective cohort study included 111 patients with MDBO who underwent MHSEMS placement between September 2022 and August 2023. The primary outcome was the recurrent biliary obstruction (RBO) rate. The secondary outcomes were adverse event (AE) rates, removability, technical and clinical success rates, and time to RBO.

The technical success rate was 100%, and the clinical success rate was 94.6%. AEs occurred in 34.2% of patients, with RBO in 21.0% and non-RBO AEs in 17.1%. RBO included stent migration in 1.9%, stent occlusion in 11.7% (including ingrowth in 5.7%, biliary debris in 2.9%, hemobilia in 1.9%, and food impaction in 1.0%), and nonocclusion cholangitis (requiring biliary drainage) in 5.7%. Non-RBO AEs included post-endoscopic retrograde cholangiopancreatography pancreatitis in 11.7%, cholecystitis in 2.7%, and nonocclusion cholangitis in 2.7%. Stent removal was successful in 88.9% of attempts. The median time to RBO was 446 days.

The placement of MHSEMS for MDBO was effective and feasible, demonstrating low migration rates, acceptable AEs, and removability.

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.

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.

Few studies compared laparoscopic and open pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy.

Retrospective cohort of patients who underwent laparoscopic or open pancreatoduodenectomy for resectable or borderline resectable pancreatic ductal adenocarcinoma after chemoradiotherapy between 2012 and 2023 was analyzed. Open pancreatoduodenectomy patients could theoretically benefit from the laparoscopic approach. We used a 1:2 (laparoscopic-to-open pancreatoduodenectomy) propensity score matching analysis stratified on age, gender, and body mass index.

We included 128 patients (33 laparoscopic and 95 open pancreatoduodenectomy), and after propensity score matching, 33 laparoscopic pancreatoduodenectomy and 66 open pancreatoduodenectomy were compared. There was no difference in demographic data except for lower tobacco use in laparoscopic pancreatoduodenectomy group (9% vs 30%, P = .023) with similar clinical presentation. Laparoscopic pancreatoduodenectomy compared to open pancreatoduodenectomy showed a longer median operative duration (380 vs 255 minutes, P < .001), shorter median length of resected vein (15 vs 23 mm, P = .01), longer median venous clamping time (29 vs 15 minutes, P = .005), similar median blood loss (300 vs 300 mL, P = .223), similar rate of hard pancreas (97% vs 85%, P = .094), and a larger median size of Wirsung duct (5 vs 4 mm, P = .02). Postoperative outcomes showed similar 90-day mortality rates (3% vs 3%, P > .99), Clavien-Dindo III-IV complications (6% vs 14%, P = .158), median lengths of hospital stay (12 vs 13 days, P = .409), and readmission rates (9% vs 18%, P = .366). Pathologic data showed similar R0 resection rates (88% vs 82%, P = .568). With a similar rate of adjuvant chemotherapy (P = .324) and shorter median follow-up with laparoscopic pancreatoduodenectomy (18 vs 34 months, P = .004), 3-year overall (P = .768) and disease-free (P = .839) survival rates were similar.

In selected patients, laparoscopic pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy appears to be safe and feasible when performed in experienced centers.

For preoperative biliary drainage of pancreatic cancer (PC), a 10-mm diameter metal stent (MS) is commonly used; however, the rate of pancreatitis is high. It is hypothesized that smaller-diameter MS may reduce the rate of pancreatitis. Therefore, we conducted a multicenter prospective study to evaluate the efficacy and safety of 7-mm MS.

Patients requiring initial biliary drainage for obstructive jaundice caused by PC and scheduled for surgery from six facilities were included. After endoscopic retrograde cholangiography, a 7-mm MS was placed at the site of biliary obstruction. The primary endpoint was the rate of pancreatitis, and the secondary endpoints included early and late adverse events (AEs). The pancreatitis rate was assumed to be 18% and 5% with 10- and 7-mm MS, respectively; with a power of 80% and one-sided significance level of 10%, the planned enrollment was 38 patients. If pancreatitis occurred in no more than three patients, this indicates that the 7-mm MS effectively reduced incidence of pancreatitis.

Overall, 38 patients were enrolled, and 35 patients in whom a 7-mm MS was successfully placed were analyzed. All MS were placed after sphincterotomy. Pancreatitis occurred in four patients (11.4%) and no early AEs were observed. Surgery was performed in 24 patients and late AEs included stent occlusion in eight patients (23%) and cholecystitis in four patients (11%).

The 7-mm MS did not reduce incidence of pancreatitis among surgical candidates for PC.

Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT.

Patients with clinical T4M0 disease in the National Cancer Database from 2010 to 2017 were included. Potential predictors were assessed by relative risk regression with Poisson distribution and compared by log-link function.

In total, 28 056 patients met the criteria. Among 17 059 (67.67%) patients treated primarily with chemotherapy, 41.19% also had radiation and 8.89% went onto resection. Many received no cancer-directed treatment or failed to receive GRT. Another 710 patients had radiation (±surgery) without chemotherapy despite few contraindications to chemotherapy. Over time, patients were more likely to undergo resection after chemotherapy (aRR = 1.58; p < 0.0001) and less likely to have chemoradiation (aRR = 0.78; p < 0.0001) or go untreated (aRR = 0.90; p < 0.0001). Socioeconomic factors (race, education, income, and insurance status) affected the likelihood of receiving chemotherapy and surgery. Median overall survival (OS) was significantly improved for patients treated with chemotherapy and particularly in those patients who went on to receive RT or undergo surgical resection. OS was also longer for patients treated at high-volume academic centers. Patients insured by Medicaid, Medicare, or those without insurance had worse OS.

Despite improvement over time, many patients go untreated. Clinical factors were influential, but the impact of vulnerable social standing suggests persistent inequity in access to care.

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.

Indicators, such as mortality and complications, are commonly used to measure the quality of care. However, a more comprehensive assessment of surgical quality is captured using composite outcome measures such as Textbook Outcome (TO), Optimal Pancreatic Surgery, and a newer 'Ideal Outcome' (IO) measure. We reviewed our institutional experience to assess the impact of demographics, comorbidities, and operative variables on IO after pancreatoduodenectomy (PD).

A retrospective study was conducted on PD patients at Northwell Health between 2009 and 2023. IO was determined by the absence of six adverse outcomes, including in-hospital mortality, Clavien-Dindo ≥ III complications, clinically-relevant postoperative pancreatic fistula, reoperation, hospital stay > 75th percentile, and readmission within 30 days. Logistic regression analyzed the effects of various factors on achieving IO.

Of the 578 patients who underwent PD, 248 (42.91%) achieved the IO. On multivariable analysis, factors associated with increased odds of achieving IO included neoadjuvant chemotherapy (OR 1.30, 95% CI 1.05-1.62) and the presence of neuroendocrine tumors (OR 3.37, 95% CI 1.35-8.41). Percutaneous transhepatic biliary drainage (PTBD) (OR 0.34, 95% CI 0.14-0.80) and older age (≥ 70 years) (OR 0.48, 95% CI 0.32-0.74) were associated with decreased odds of achieving IO. Patients with IO had significantly improved survival on Kaplan-Meier log-rank test (p = 0.001) as well as adjusted Cox analysis (HR 0.62 95% CI: 0.39-0.97).

IO may offer a comprehensive metric for assessing PD outcomes, highlighting the impact of age, chemotherapy, biliary drainage, and tumor types. These findings suggest targeted interventions and quality improvements could enhance PD outcomes by addressing modifiable factors and refining clinical strategies.

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.

This study aimed to compare the long-term effects of neoadjuvant therapy and upfront surgery on overall survival (OS) and progression-free survival (PFS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC).

We retrospectively analyzed 202 patients, including 167 who had upfront surgery and 35 who received neoadjuvant therapy followed by surgery. Surgical outcomes and survival rates were compared using propensity score matching to minimize selection bias.

Neoadjuvant therapy showed significantly longer 75% OS (72.7 months vs. 28.3 months, p = 0.032) and PFS (29.6 months vs. 13.2 months, p < 0.001) compared to upfront surgery. Additionally, neoadjuvant therapy demonstrated significant improvements in surgical outcomes, including higher R0 resection rates (74.3% vs. 49.5%, p = 0.034), reduced tumor size (22.0 mm vs. 28.0 mm, p = 0.001), and decreased lymphovascular invasion (20.0% vs. 52.4%, p = 0.001).

Our study demonstrates the potential benefits of neoadjuvant therapy for resectable PDAC. The improved survival rates, delayed disease progression, and enhanced surgical outcomes underscore the potential of neoadjuvant therapy in addressing this aggressive disease. Despite limitations such as the retrospective design and small sample size, these findings support the effectiveness of neoadjuvant therapy in improving treatment outcomes for PDAC patients in real-world settings. Further prospective studies are required to validate these results.

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite the improvement of multi-modality treatment strategies, the prognosis of pancreatic cancer was not improved dramatically. For resectable or borderline resectable patients, the surgical strategy centered on improving R0 resection rate is consensus; however, the role of neoadjuvant therapy in resectable patients and the optimal neoadjuvant therapy of chemotherapy with or without radiotherapy in borderline resectable patients were debated. Postoperative adjuvant chemotherapy of gemcitabine/capecitabine or mFOLFIRINOX is recommended regardless of the margin status. Chemotherapy as the first-line treatment strategy for advanced or metastatic patients included FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan was the only standard of care second-line therapy. Immunotherapy is an innovative therapy although anti-PD-1 antibody is currently the only agent approved by for MSI-H, dMMR, or TMB-high solid tumors, which represent a very small subset of pancreatic cancers. Combination strategies to increase the immunogenicity and to overcome the immunosuppressive tumor microenvironment may sensitize pancreatic cancer to immunotherapy. Targeted therapies represented by PARP and KRAS inhibitors are also under investigation, showing benefits in improving progression-free survival and objective response rate. This review discusses the current treatment modalities and highlights innovative therapies for pancreatic cancer.

The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations.

This research aimed to assess the value of radiomics combined with multiple machine learning algorithms in the diagnosis of pancreatic ductal adenocarcinoma (PDAC) lymph node (LN) metastasis, which is expected to provide clinical treatment strategies.

A total of 128 patients with pathologically confirmed PDAC and who underwent surgical resection were randomized into training (n=93) and validation (n=35) groups. This study incorporated a total of 13 distinct machine learning algorithms and explored 85 unique combinations of these algorithms. The area under the curve (AUC) of each model was computed. The model with the highest mean AUC was selected as the best model which was selected to determine the radiomics score (Radscore). The clinical factors were examined by the univariate and multivariate analysis, which allowed for the identification of factors suitable for clinical modeling. The multivariate logistic regression was used to create a combined model using Radscore and clinical variables. The diagnostic performance was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA).

Among the 233 models constructed using arterial phase (AP), venous phase (VP), and AP+VP radiomics features, the model built by applying AP+VP radiomics features and a combination of Lasso+Logistic algorithm had the highest mean AUC. A clinical model was eventually constructed using CA199 and tumor size. The combined model consisted of AP+VP-Radscore and two clinical factors that showed the best diagnostic efficiency in the training (AUC = 0.920) and validation (AUC = 0.866) cohorts. Regarding preoperative diagnosis of LN metastasis, the calibration curve and DCA demonstrated that the combined model had a good consistency and greatest net benefit.

Combining radiomics and machine learning algorithms demonstrated the potential for identifying the LN metastasis of PDAC. As a non-invasive and efficient preoperative prediction tool, it can be beneficial for decision-making in clinical practice.

Erythrocytes and fibroblasts in the pancreatic cancer tumor microenvironment promote tumor cell growth and invasion by providing nutrients and promoting immunosuppression. Additionally, they form a barrier against the penetration of chemotherapeutic drugs. Therefore, the search for diversified tumor-targeting materials plays an essential role in solving the above problems.

Physicochemical characterization of Graphene fluorescent nanoparticles (GFNPs) and nanomedicines were analyzed by transmission electron microscopy (TEM), elemental analyzers and ultraviolet fluorescence (UV/FL) spectrophotometer. Localization of GFNPs in cell and tissue sections imaged with laser confocal microscope, fluorescence scanner and small animal in vivo imager. Qualitative detection and quantitative detection of GFNPs and GFNPs-GEM were performed using High performance liquid chromatography (HPLC).

Based on the 3 nm average dimensions, GFNPs penetrate vascular endothelial cells and smooth muscle cells, achieve up to label 30% tumor cells and 60% cancer-associated fibroblasts (CAFs) cells, and accurately label mature red blood cells in the tumor microenvironment. In orthotopic transplanted pancreatic cancer models, the fluorescence intensity of GFNPs in tumors showed a positive correlation with the cycle size of tumor development. The differential spatial distribution of GFNPs in three typical clinical pancreatic cancer samples demonstrated their diagnostic potential. To mediate the excellent targeting properties of GFNPs, we synthesized a series of nanomedicines using popular chemotherapeutic drugs, in which complex of GFNPs and gemcitabine (GFNPs-GEM) possessed stability in vivo and exhibited effective reduction of tumor volume and fewer side effects.

GFNPs with multiple targeting tumor microenvironments in pancreatic cancer possess diagnostic efficiency and therapeutic potential.

The purpose of preoperative biliary drainage (PBD) is to reduce complications during the perioperative period. The extrahepatic bile duct comprises distal and hilar bile ducts and assessing the need for PBD must be considered separately for each duct, as surgical procedures and morbidities vary. The representative disease-causing distal bile duct obstruction is pancreatic cancer. A randomized controlled trial has revealed that PBD carries the risk of recurrent cholangitis and pancreatitis before surgery, thus eliminating the need for PBD when early surgery is feasible. However, neoadjuvant therapy has seen a rise in recent years, resulting in longer preoperative waiting periods and an increased demand for PBD. In such cases, metal stents are preferable to plastic stents due to their lower stent occlusion rates. When endoscopic transpapillary biliary drainage (EBD) is not viable, endoscopic ultrasound-guided biliary drainage may be a suitable substitute. In the hilar bile duct, the representative disease-causing obstruction is hilar cholangiocarcinoma. PBD's necessity has long been a subject of contention. In spite of earlier criticisms of routine PBD, recent views have emerged recommending PBD, particularly when major hepatectomy is required, to prevent postoperative liver failure. Given the risk of tumor seeding associated with percutaneous transhepatic biliary drainage, EBD is preferable. Nevertheless, as its shortcomings involve recurrent cholangitis until surgery due to stent or tube obstruction, it is necessary to seek out novel approaches to circumvent complications. In this review we summarize the current evidence for PBD in patients with distal and hilar biliary obstruction.

Pancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT).

We analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD.

The occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct-parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08-4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10-3.72, p = 0.023), in multivariate analysis.

Pancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition.

Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC.

A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI).

Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference).

Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.

Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown.

We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model.

Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02).

NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use.

The authors reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, The Cochrane Library, Web of Science from 2009 to 2023 to estimate relative odds ratios for resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials.

A total of nine studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer (RPC) patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline RPC. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer.

The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline RPC. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.

Pancreatic ductal adenocarcinoma (PDAC), which is notorious for its aggressiveness and poor prognosis, remains an area of great unmet medical need, with a 5-year survival rate of 10% - the lowest of all solid tumours. At diagnosis, only 20% of patients have resectable pancreatic cancer (RPC) or borderline RPC (BRPC) disease, while 80% of patients have unresectable tumours that are locally advanced pancreatic cancer (LAPC) or have distant metastases. Nearly 60% of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy (CHT) because of postoperative complications and early cancer recurrence. An important paradigm shift to achieve better outcomes has been the sequence of therapy, with neoadjuvant CHT preceding surgery. Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers: RPC, BRPC, and LAPC. The main goal of neoadjuvant treatment (NAT) is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT, reducing tumour volume before surgery to improve the rate of margin-negative resection (R0 resection, a microscopic margin-negative resection), reducing the rate of positive lymph node occurrence at surgery, providing early treatment of occult micrometastatic disease, and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria. In this editorial, we summarize evidence concerning NAT of PDAC, providing insights into future practice and study design. Future research is needed to establish predictive biomarkers, measures of therapeutic response, and multidisciplinary strategies to improve patient-centered outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters.

Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.

PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).

With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.

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.

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.

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).

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.

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.

Within the past decade, minimally invasive pancreaticoduodenectomy has been increasingly adopted in high-volume cancer centers. Amid broader trends of a growing older population, the numbers of frail patients with cancer are expected to increase. In this study, we compared the postoperative outcomes of open pancreaticoduodenectomy and minimally invasive pancreaticoduodenectomy in frail patients with pancreatic ductal adenocarcinoma.

Using the pancreatectomy-targeted American College of Surgeons-National Surgical Quality Improvement Program database (2014-2021), we identified pancreaticoduodenectomy cases for pancreatic ductal adenocarcinoma. Patients with a modified frailty index ≥2 were considered frail. We performed 2:1 (open pancreaticoduodenectomy to minimally invasive pancreaticoduodenectomy) optimal pair propensity score matching for both patient- and disease-specific characteristics. We evaluated baseline covariate balance for homogeneity and assessed 30-day postoperative outcomes: complications, discharge destination, major morbidity, and mortality.

We identified 3,143 frail patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. Of those, 275 (9%) underwent minimally invasive pancreaticoduodenectomy. Minimally invasive pancreaticoduodenectomy was associated with a lower rate of any complications compared with open pancreaticoduodenectomy (43% vs 54%; P < .001), major morbidity (29% vs 35%; P = .042), and nonhome discharge (12% vs 17%; P = .022). When comparing the 2 minimally invasive pancreaticoduodenectomy approaches, robotic surgery was associated with fewer complications compared with laparoscopy (39% vs 51%; P = .040) and a lower mortality rate (1% vs 4%; P = .041) CONCLUSION: In frail patients with pancreatic cancer, minimally invasive pancreaticoduodenectomy was associated with better postoperative outcomes than open pancreaticoduodenectomy. This study builds on growing literature reporting that, when properly implemented, minimally invasive pancreaticoduodenectomy is associated with more favorable postoperative outcomes. Given the particularly high risk of complication in frail patients, implementing a preoperative frailty assessment can provide valuable insights to inform patient counseling.

Neoadjuvant therapy (NT) is increasingly recommended for patients with localized pancreatic ductal adenocarcinoma (PDAC). Recent research has highlighted the significant treatment burden that patients experience during NT, but caregiver well-being during NT is poorly understood.

A cross-sectional mixed-methods analysis of primary caregivers of patients with localized PDAC receiving NT was undertaken. All patients completed the Caregiver Quality of Life Index-Cancer (CQOLC) survey, while semi-structured interviews were conducted among a convenience sample of participants.

Among 28 caregivers, the mean age was 60.1 years, and most were patient spouses/significant others (71.4%). Patients had resectable (18%), borderline resectable (46%), or locally advanced (36%) PDAC with a mean treatment duration of 2.9 months at the time of their caregiver's enrollment. Most caregivers felt that they received adequate emotional/psychosocial support (80%) and understood the rationale for NT (93%). A majority (60%) reported that caregiving responsibilities impacted their daily lives and required a decrease in their work hours, leading to financial challenges (47%). While overall QOL was moderate (mean 83 ± 21.1, range 0-140), "emotional burden" (47.3 ± 20.9), and "positive adaption" (57.3 ± 13.9) were the lowest ranked CQOLC subsection scores.

Caregivers of patients with PDAC undergoing NT experience significant emotional symptoms and impact on their daily lives. Assessing caregiver needs and providing resources during NT should be a priority.