Neoadjuvant chemotherapy (NAC) treatment has appeared as a promising alternative to upfront surgery to improve efficacy outcomes in non-metastatic colon cancer, but the findings are still controversial. Considering this ongoing debate, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the benefit of NAC in high-risk stage II and stage III colon cancer.

We searched PubMed, Embase, and Cochrane for clinical trials evaluating NAC in non-metastatic colon cancer. Random and fixed effects models were employed for statistical analyses in Review Manager software version 5.4. Moreover, to evaluate the heterogeneity, I2 statistics were used.

A total of 1248 patients from 4 clinical trials were included. The NAC group demonstrated a 38 % reduction in the risk of death. (HR 0.62; 95 % CI 0.41-0.92; I2 = 0 %), and a 21 % reduction in the risk of disease recurrence (HR 0.79; 95 % CI 0.65-0.96; I2 = 0 %). Additionally, the NAC group had higher R0 resection, with an increase of 80 % in the odds compared to upfront surgery (OR 1.80; 95 % CI 1.24-2.61; I² = 0 %). Pathological complete response and major pathologic response (PCR) were achieved in 5.9.% % and 36.2 %, respectively. Patients with proficient mismatch repair achieved a higher PCR rate and a consistent reduction in the risk of recurrence compared to the overall population, with proportions of 6.3 % and 32 %, respectively. Also, there was no significant addition to the toxicity profile in the NAC arm.

Our systematic review and meta-analysis support the feasibility and survival benefits of neoadjuvant chemotherapy for high-risk stage II and III colon cancer.

This study assesses trends in resection rates and postoperative mortality for oesophageal, gastric, colon, rectal, periampullary and pancreatic cancer in the Netherlands.

This retrospective cohort study included all patients with gastrointestinal cancer diagnosed in the period 2005-2020 as registered in the Netherlands Cancer Registry. Cochran-Armitage trend tests were used to assess trends in resection rates. Multivariable logistic regression analyses were used to assess the association between time period and resection rates and postoperative mortality and were stratified for nonmetastatic versus metastatic disease at initial diagnosis.

A total of 226 925 patients with nonmetastatic and 92 343 with metastatic disease were included. A lower likelihood of undergoing resection was observed for patients diagnosed between 2017 and 2020 as compared to 2005-2008 for nonmetastatic colon (OR=0.73; 95 %CI:0.68-0.79) and rectal cancer (OR=0.44; 95 %CI:0.40-0.48). In contrast, higher resection rates were observed for nonmetastatic gastric (OR=1.17; 95 %CI:1.03-1.32), periampullary (OR=2.44;95 %CI:2.09-2.84) and pancreatic cancer (OR=2.81; 95 %CI:2.51-3.15 comparing the same time periods). Patients with nonmetastatic disease diagnosed in 2017-2020 had a lower likelihood of 90-day postoperative mortality compared to 2005-2008 for all cancer types with ORs ranging between 0.27 (95 %CI:0.22-0.33, rectal cancer) and 0.60 (95 %CI:0.43-0.84, periampullary cancer). In colon and rectal cancer patients presenting with metastatic disease, resection rates and postoperative mortality significantly decreased over time.

Resection rates decreased for some gastrointestinal cancer types possibly due to the introduction of treatment strategies without resection (e.g. watchful waiting). Postoperative mortality decreased for all patients, possibly as a result of increased quality of care, and improved patient selection.

In pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), Prophylactic right-half dissection of the superior mesenteric artery (SMA) nerve plexus has been attempted in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In this study, we evaluated the significance of prophylactic right-half dissection of the SMA nerve plexus by extending the observation period to 5 years.

From April 2014 to June 2018, 74 patients with PDAC in the pancreatic head were randomly assigned to either the dissection group, in which the right half of the nerve plexus of the SMA was dissected (n = 37) or the preservation group, in which the nerve plexus of the SMA was completely preserved (n = 37). The 5-year relapse-free survival (RFS), overall survival (OS), and incidence of diarrhea were prospectively compared between groups.

The median RFS (20 vs. 16 months, P = 0.503) and OS (37.0 vs. 30.0 months, P = 0.582) did not differ significantly between the dissection and preservation groups. There was no significant difference in locoregional recurrence (27.0% vs. 37.8%, P = 0.320) or distant metastasis (64.9% vs. 83.0%, P = 0.451). Postoperative diarrhea occurred in 64.9% and 62.2% of the cases in the dissection and preservation groups, respectively (P = 0.809).

Prophylactic right half dissection of the SMA nerve plexus did not improve the RFS or OS.

More than 30% of patients with pancreatic cancer are unresectable because of the local extension with a median overall survival (OS) of <1 year. Combination of fluorouracil (FU), oxaliplatin, and irinotecan (FOLFIRINOX) is superior to gemcitabine in the treatment of metastatic pancreatic cancer, but standard of care remains gemcitabine in locally advanced pancreatic cancer (LAPC).

Patients with histologically proven LAPC not suitable for surgery, Eastern Cooperative Oncology Group WHO performance status (PS) ≤1 were eligible. Random assignment was stratified by center, tumor localization (pancreas head yes/no), WHO PS (0 v 1), and age (≤60 years v >60 years). Patients received FOLFIRINOX or gemcitabine for 6 months. The primary end point was progression-free survival (PFS). Main secondary end points were OS, time to treatment failure, quality of life, and safety. One hundred seventy patients (142 events) were needed to detect an increase of 3 months in PFS with 80% power (log-rank test, 5% two-sided α).

One hundred seventy one patients age 35-84 years were included and followed for a maximum of 5 years. With a median follow-up of 59.6 months (95% CI, 42.3 to not reached), 168 events were observed and the median PFS was 9.7 months (95% CI, 7.0 to 11.7) with FOLFIRINOX versus 7.7 months (95% CI, 6.2 to 9.2) with gemcitabine, hazard ratio (HR), 0.7 (95% CI, 0.5 to 1.0), P = .04. The median OS was 15.7 months (95% CI, 11.9 to 20.4) in the FOLFIRINOX group versus 15.4 months (95% CI, 11.7 to 18.6) in the gemcitabine group, HR, 1.02 (95% CI, 0.73 to 1.43), P = .95.

Results confirm that FOLFIRINOX improves PFS significantly compared with gemcitabine and is well tolerated in LAPC. No significant difference in OS was observed between both groups.

The efficacy of preoperative chemoradiotherapy (CRT) for anatomically resectable pancreatic adenocarcinoma (R-PDAC) remains contentious. This study aims to elucidate the treatment outcomes of preoperative CRT for R-PDAC and to identify prognostic factors. This retrospective study included 109 R-PDAC patients treated with gemcitabine- or S-1 plus gemcitabine-based preoperative CRT from February 2005 to April 2023. Cox proportional hazards regression was employed to identify factors associated with worse overall survival (OS). Among the 109 cases, 90 patients (82.6%) underwent curative-intent resection following CRT. The median OS for the entire cohort was 36.5 months, significantly longer in resected cases than in unresected cases (40.6 vs 11.4 months). Multivariate analysis identified pretreatment serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) and the Eastern Cooperative Oncology Group performance status ≥1 as independent prognostic factors. When these factors were scored (risk score 0-3) using pre-CRT serum CA19-9 level (≥640 U/mL) and CEA (≥6.1 ng/mL), OS for risk scores 1 (n = 41), 2 (n = 20) or 3 (n = 6) was significantly shorter than for risk score 0 (n = 42) (score 0 vs 1 vs 2 vs 3: 49.1 vs 33.8 vs 16.1 vs 16.8 months). The presence of portal vein invasion on imaging and post-CRT serum CA 19-9 level (≥111 U/mL) were independent prognostic factors in resected cases. Biological factors, including serum levels of CA19-9 and CEA, along with conditional factor of Eastern Cooperative Oncology Group performance status ≥1, were identified as independent prognostic factors for R-PDAC patients treated with preoperative CRT. Preoperative CRT is considered effective for cases lacking these risk factors.

While anatomical resectability guides pancreatic cancer treatment, carbohydrate antigen (19-9 (CA19-9) serves as a biological indicator of disease burden. Current guidelines suggest considering neoadjuvant chemotherapy (NAC) for cases with markedly elevated CA19-9, but specific threshold values and treatment strategies remain undefined. This retrospective study aimed to evaluate the efficacy of intensive NAC using gemcitabine plus nab-paclitaxel or fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) for anatomically resectable pancreatic cancer with elevated CA19-9 (> 500 U/mL).

We analyzed patients with anatomically resectable pancreatic cancer and CA19-9 > 500 U/mL treated between 2014 and 2022. Initial planned treatments were either 4-month intensive NAC followed by surgery (NAC group) or upfront surgery (UPS group). Survival outcomes were evaluated using retrospective intention-to-treat analysis.

Among 184 included patients, 46 received NAC and 138 underwent upfront surgery. The NAC group demonstrated significantly improved overall survival compared with the UPS group (median 52.7 vs. 22.7 months, P < 0.001). Resection rates were 89.1% and 76.1% in the NAC and UPS groups, respectively. Among resected cases, the NAC group achieved higher lymph node-negative resection rates (53.7% vs. 23.8%, P < 0.001) and better post-resection CA19-9 normalization rates (75.6% vs. 56.1%, P = 0.037). Survival benefits were maintained even in cases with CA19-9 > 2000 U/mL (median OS 52.7 vs. 18.9 months, P = 0.025).

CA19-9 > 500 U/mL serves as an effective indicator for implementing intensive NAC in anatomically resectable pancreatic cancer. This biomarker-based strategy effectively extracts the beneficial group from NAC, prolonging survival outcomes through better systemic disease control.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers. Surgical resection combined with appropriate chemotherapy currently offers the best chance for long-term survival and potential cure. However, effective treatment is hindered by the limited chemotherapy options and the absence of reliable clinical tools to guide chemotherapy selection. Patient-derived organoids (PDOs) have emerged as a promising technology with the potential in precision medicine for PDAC. This review provides an overview of pancreatic organoid genesis, explores the role of PDOs in elucidating PDAC biology within clinically relevant contexts, and concludes by examining current literature on the utility of PDOs as biomarkers for personalized treatment strategies.

The anatomically resectable pancreatic ductal adenocarcinoma treatment sequence is still debated. Heterogeneity in patient characteristics within this group may explain literature discrepancies. To overcome these limits, a biologically borderline resectable pancreatic ductal adenocarcinoma category has been analysed according to institutional criteria. The aim of this study was to examine the characteristics and outcomes of patients with biologically borderline resectable pancreatic ductal adenocarcinoma and determine whether they represent a distinct clinical and prognostic subgroup.

Data from all consecutive patients who underwent surgical resection for pancreatic ductal adenocarcinoma between 2015 and 2022 were retrospectively analysed. Biologically borderline resectable disease was classified by the presence of one or more of the following: carbohydrate antigen 19-9 ≥200 U/ml, cancer-related symptoms lasting >40 days, and radiological suspicion of regional lymph node metastases at diagnosis.

In total, 886 patients were included in the study and divided into anatomically borderline resectable (266 patients (30%)) and anatomically resectable (620 patients (70%)), which was further divided into resectable (R; 397 patients (64%)) and biologically borderline resectable (223 patients (36%)). Neoadjuvant treatment was administered in 245 patients (92.1%) in the anatomically borderline resectable group, 82 patients (20.7%) in the R group, and 135 patients (60.5%) in the biologically borderline resectable group. After a median follow-up of 45 (95% c.i. 42 to 48) months, the median disease-specific survival in the biologically borderline resectable group was 40 months compared with 59 months in the R group (P < 0.001) and 40 months in the anatomically borderline resectable group (P = 0.570). In the upfront surgery cohort, the median disease-specific survival was worse for biologically borderline resectable patients compared with R patients (27 versus 54 months respectively, P < 0.001). Biologically borderline resectable was also independently associated with worse disease-specific survival, together with age, tumour size at diagnosis, and anatomically borderline resectable. The same, except for age, were also predictors of worse event-free survival.

Despite their identical anatomical appearance, resectable and biologically borderline resectable pancreatic ductal adenocarcinoma represent two distinct prognostic entities, warranting separate evaluation and, potentially, different treatment approaches.

Research studies aimed at improving the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have brought about limited progress, and in clinical practice, the optimized use of surgery, chemotherapy and supportive care have led to modest improvements in survival that have probably reached a plateau. As a result, PDAC is expected to be the second leading cause of cancer-related death in Western societies within a decade. The development of therapeutic advances in PDAC has been challenging owing to a lack of actionable molecular targets, a typically immunosuppressive microenvironment, and a disease course characterized by rapid progression and clinical deterioration. Yet, the progress in our understanding of PDAC and identification of novel therapeutic opportunities over the past few years is leading to a strong sense of optimism in the field. In this Perspective, we address the aforementioned challenges, including biological aspects of PDAC that make this malignancy particularly difficult to treat. We explore specific areas with potential for therapeutic advances, including targeting mutant KRAS, novel strategies to harness the antitumour immune response and approaches to early detection, and propose mechanisms to improve clinical trial design and to overcome various community and institutional barriers to progress.

To develop a score system including CT features for predicting postoperative early (≤ 1 year) recurrence-free survival (RFS) in resectable pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical resection and assess its performance.

This dual-center, retrospective study included patients with resectable PDAC who underwent radical resection from September 2016 to April 2023. All CT features were independently evaluated by two blinded radiologists. An early recurrence score (ERS) based on CT and clinical features, for predicting early recurrence risk, was developed by Cox regression analysis in the developing cohort, and was validated in the testing and validation cohorts and compared with AJCC TNM staging system.

This study included 210 patients in the development cohort (mean age ± standard deviation, 60 ± 10 years; 129 men), 92 patients in the testing cohort (60 ± 9 years; 60 men), and 31 patients in the validation cohort (62 ± 7 years; 20 men). CA19-9 (hazard ratio [HR], 1.57; p = 0.044), perineural invasion on CT (HR, 1.83; p = 0.037), tumor necrosis (HR, 3.20; p < 0.001), and lymph nodes metastasis on CT (HR, 1.84; p = 0.004) formed the ERS. Its AUC of 0.851 and 0.901, superior to AJCC TNM staging (AUC of 0.630 and 0.534) in the testing and validation cohorts, (p < 0.05), respectively. The high-risk patients predicted by ERS had significantly higher postoperative 1-year recurrence rates than their low-risk counterparts in both the testing cohort (81.4% vs 22.5%, p < 0.001) and the validation cohort (81.2% vs 26.7%, p = 0.003).

The ERS noninvasively predicted early recurrence in resectable PDAC, outperforming the AJCC TNM system.

Question More accurately risk-stratifying PDAC patients would allow for better treatment planning. Findings Perineural invasion on CT, lymph nodes metastasis on CT, tumor necrosis, and CA19-9 were associated with early recurrence of resectable PDAC. Clinical relevance The ERS system showed better predictive performance for early recurrence in resectable PDAC and outperformed the American Joint Commission on Cancer TNM system.

Pancreatic adenocarcinoma (PAC) is notorious for its poor survival. The provision of survival scenarios-that is, best-case, typical and worst-case scenarios-could prove valuable to patients and clinicians. This study investigated survival scenarios and how these have changed over a period of 16 years for patients with PAC. Data from the Netherlands Cancer Registry were used to identify patients with localized and metastatic PAC (2005-2021). Survival scenarios, including best-case, upper-typical, typical (median), lower-typical, and worst-case, were estimated based on survival curve percentiles (p10, p25, p50, p75, and p90). Annual differences were assessed for significance using weighted linear regression analyses. Factors associated with these scenarios were identified through univariable tests. Overall, 14,622 patients with localized and 20,199 with metastatic PAC were included. For patients with localized PAC, the best, upper-typical and typical survival scenarios improved statistically significant with average annual improvement of 1.54 (95%CI: 1.2-1.88), 0.67 (0.56-0.78), and 0.24 (0.19-0.29) months, respectively. For patients with metastatic PAC the best and upper-typical survival scenarios increased statically significantly with annual improvement of 0.28 (0.21-0.34) and 0.06 (0.02-0.09) months, respectively. The best-case and upper-typical scenarios were associated with younger patients, more aggressive disease-focused treatments, fewer comorbidities, and better overall performance status. Over the past 16 years, survival improvements in patients with PAC have been most notable in these scenarios. Although the absolute gains were modest, these results offer encouraging potential for advancements in life-prolonging care for this type of cancer.

Neoadjuvant chemotherapy (NAC) can improve the survival outcomes of patients with pancreatic cancer, but for borderline resectable pancreatic cancer (BRPC) the proportion of conversion to surgery remains unsatisfactory. This single-arm pilot study aimed to assess the clinical efficacy and safety of NAC based on patient-derived organoids (PDOs) for BRPC.

Biopsy samples from BRPC patients were collected for generating PDOs. Gemcitabine plus nab-paclitaxel as NAC was initially administrated for one cycle, and then the treatment regimen was adjusted based on the PDO drug sensitivity testing. The primary endpoint was the objective response rate (ORR). Secondary endpoints included R0 resection rate, NAC-related adverse events (AEs), and postoperative complications. Exploratory objectives were to assess the chemoresistance to gemcitabine.

Totally 19 of 25 patients were eligible for the study, among whom 16 achieved partial response and received surgical resection, with the ORR of 84.2% (16/19). The R0 resection rate was 81.3% (13/16). During NAC, 8 (42.1%, 8/19) patients experienced different grades of AEs, mainly including grade 2 myelosuppression (26.3%), cutaneous pruritus (5.3%), and diarrhea (5.3%). scRNA-seq analysis of duct cells showed that the transcriptome in aneuploid cells may affect gemcitabine resistance via multiple pathways, among which upregulation of drug-resistant genes ( OLFM4, AGR2, MUC5AC, MUC1, HMGA1, REG4, IL17RB, GCNT3, AKR1B10, ITGA6, HMGCS2 , and SQLE ) and downregulation of sensitive genes ( SIK1, HEXIM1, SPINT2, GADD45 , and TIMP2 ) played crucial roles. Changes in the interactions between cancer cells and other cell groups may also involve in gemcitabine resistance.

PDO-based NAC shows a promising resectable rate in BRPC patients, with good tolerance. Potential drug-resistant and sensitive genes and cell-cell interaction changes may participate in the development of gemcitabine resistance.

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.

Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery.

This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated.

Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement.

Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

As the population ages, the number of octogenarians with pancreatic ductal adenocarcinoma (PDAC) continues to rise. Morbidity and mortality following pancreatectomy have improved owing to safer surgery and better chemoradiation regimens. This study compares the outcomes and multimodality utilization in octogenarians (≥80 years) who underwent pancreaticoduodenectomy (PD) for PDAC, with a younger cohort.

This is a multi-institutional retrospective review from 2007 to 2023 of patients who underwent PD for PDAC. Preoperative, perioperative, and oncologic outcomes were analyzed, and multivariable analysis (MVA) was performed.

A total of 1,051 patients underwent PD for PDAC ( ≥ 80 = 125, < 80 = 926). Octogenarians had a higher age unadjusted Charlson Comorbidity Index (p = 0.0146) and were more likely to have prior abdominal surgery (p = 0.0019). Patients <80 years received chemotherapy (p < 0.0001) or radiation (p < 0.0001), including neoadjuvant chemotherapy (p < 0.0001), more frequently than octogenarians, who more commonly underwent upfront surgery (p < 0.0001). There were no significant differences in complications. Octogenarians had a higher 90 day mortality rate (7.2% versus 3.5%, p = 0.0424); however, this was not significant on MVA. The <80 cohort had longer overall survival (OS) (p = 0.0004). Receiving any chemotherapy was associated with longer OS (hazard ratio [HR] 0.59 [0.46-0.75], p < 0.0001). In survival analysis of octogenarians only, receiving multimodal therapy significantly prolonged OS compared with surgery alone (p = 0.0349).

Octogenarian status does not increase morbidity or mortality but is associated with decreased survival in PDAC patients undergoing PD. Chemotherapy had a protective effect on OS; however, octogenarians received less multimodal therapy compared with the younger cohort.

BackgroundThe role of neoadjuvant chemotherapy (NAT) in patients with resectable pancreatic cancer is being studied in ongoing multicenter randomized trials. The primary aim of this study is to compare survival between NAT and up-front surgery (UFS) in a non-selected population of patients presenting with resectable cancer of the head of the pancreas. Patient and tumor-related factors impacting receipt of NAT and survival were also analyzed.MethodsA single institution prospective database was queried to identify patients who underwent pancreaticoduodenectomy for resectable pancreatic adenocarcinoma from 2019 to 2023. Patient demographic and clinical oncologic factors were compared between those who received NAT and those who underwent UFS. Area Deprivation Index (ADI) and distance traveled were used as surrogate indicators for socioeconomic disparity and rurality, respectively. Overall survival was compared using Kaplan-Meier and Cox Regression analyses.ResultsOf the 83 patients included, one third received NAT. There was no significant difference in 1 yr, 3 yr, or overall survival between patients who received NAT vs up-front surgery. ADI and distance traveled did not impact whether a patient received NAT or survival. On Multivariate Cox Regression analysis, age and performance status were the only factors significantly associated with survival.ConclusionsThere was no significant difference in early mortality and overall survival between NAT and UFS groups.

To identify the prognostic factors that can define biologically borderline resectable pancreatic cancer (BRPC) in resectable pancreatic cancer (RPC) patients.

This retrospective study included 121 R/BRPC patients who underwent upfront surgery. Univariate and multivariate analyses were conducted to investigate the relationship between preoperative factors and overall survival (OS) for RPC. The OS of RPC patients was stratified based on a score, with each independent prognostic factor receiving 1 point. The OS of the R/BRPC patients was compared based on their scores.

Overall, 113 and eight patients had RPC and BRPC. Serum CA19-9 > 500 U/mL (p = 0.048), maximum tumor diameter > 30 mm (p = 0.01), superior mesenteric/portal vein contact < 180° (p = 0.04), and minimum apparent diffusion coefficient (ADCmin) ≤ 1020 × 10-6 mm2/s (p = 0.01) were identified as independent prognostic factors in RPC patients. RPC patients with a score of 0 had a significantly better prognosis than those with scores of 1 and 2-4 and BRPC patients (median OS: 99.3, 35.1, 19.0, and 8.4 months; p = 0.007, p < 0.001, and p = 0.003, respectively). No significant difference in the prognosis was observed between BRPC and RPC patients with scores of 1 and 2-4.

Preoperative ADCmin in RPC may be a new prognostic factor for biological BRPC.

We investigated the association between serum MUC5AC (sMUC5AC) levels and patient outcomes in individuals who underwent resection for pancreatic ductal adenocarcinoma (PDA), including those treated with neoadjuvant therapy (NAT) and those who had upfront surgery (UpS) followed by adjuvant therapy.

Serum samples from the Ohio State University biorepository collected from January 2010 to June 2021 were utilized. The human MUC5AC kit (NBP2-76703) was used to perform enzyme-linked immunoassays to measure sMUC5AC levels. Logistic regression, Cox regression models (univariate and multivariate), recurrence prediction, analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis.

In the NAT cohort (n = 23), elevated sMUC5AC levels were significantly (P < 0.05) associated with pathological treatment response, margin positivity, and residual disease. Among 21 patients who had an R0/R1 resection (R2 resection, n=2), higher sMUC5AC levels were associated with shorter progression-free survival (PFS) (HR: 1.64, P = 0.0006) and overall survival (OS) (HR: 1.6, P = 0.005) on univariate analysis. Multivariate models confirmed sMUC5AC as an independent predictor of PFS and OS alongside pathological differentiation and postoperative therapy. Patients with lower sMUC5AC levels had more favorable pathological characteristics, better treatment responses, and improved survival outcomes. These findings were consistent in the FOLFIRINOX subgroup (n = 17). In the UpS cohort (n = 17), post-resection sMUC5AC levels tend to be associated with PFS (P = 0.07) and OS (P = 0.05). Combining sMUC5AC with Carbohydrate antigen (CA) 19-9 enhanced sensitivity (79%) and specificity (67%) to predict recurrence. Higher sMUC5AC levels were associated with earlier recurrence and poor survival outcomes, highlighting its utility in post-surgery risk stratification. Among patients with pre-treatment data (n = 11), sMUC5AC levels were significantly higher among patients with poorly differentiated tumors.

This study provides compelling evidence for the clinical utility of sMUC5AC as a prognostic biomarker among patients with resected PDA. Future large-scale studies are needed to validate these findings and establish standard thresholds for sMUC5AC integration into clinical practice.

Pancreatic cancer (PC) is a highly lethal malignancy, with pancreatic ductal adenocarcinoma (PDAC) being the most common and aggressive subtype, characterized by late diagnosis, aggressive progression, and resistance to conventional therapies. Despite advances in understanding its pathogenesis, including the identification of common genetic mutations (e.g., KRAS, TP53, CDKN2A, SMAD4) and dysregulated signaling pathways (e.g., KRAS-MAPK, PI3K-AKT, and TGF-β pathways), effective therapeutic strategies remain limited. Current treatment modalities including chemotherapy, targeted therapy, immunotherapy, radiotherapy, and emerging therapies such as antibody-drug conjugates (ADCs), chimeric antigen receptor T (CAR-T) cells, oncolytic viruses (OVs), cancer vaccines, and bispecific antibodies (BsAbs), face significant challenges. This review comprehensively summarizes these treatment approaches, emphasizing their mechanisms, limitations, and potential solutions, to overcome these bottlenecks. By integrating recent advancements and outlining critical challenges, this review aims to provide insights into future directions and guide the development of more effective treatment strategies for PC, with a specific focus on PDAC. Our work underscores the urgency of addressing the unmet needs in PDAC therapy and highlights promising areas for innovation in this field.

Positron Emission Tomography/Computed Tomography (PET/CT) plays a critical role in managing gastrointestinal (GI) cancers within radiation oncology. It enhances tumor detection, staging, and lymph node involvement assessment, leading to better-targeted radiation treatment. PET/CT also aids in delineating tumor volumes to minimize geographic misses, enabling precise dose escalation to metabolically active regions. Despite its benefits, PET/CT has limitations such as false positives and dependency on complementary imaging. Emerging technologies offer real-time adjustments and personalized treatments, advancing precision medicine in GI radiation oncology. Further research is needed to refine PET/CT integration for improved treatment outcomes and cost-effectiveness.

With the advent of improved chemotherapy options, neoadjuvant chemotherapy has gained acceptance as a multidisciplinary treatment approach for localized pancreatic ductal adenocarcinoma. This study aimed to clarify whether neoadjuvant chemotherapy with gemcitabine and S-1 influences preoperative nutritional status and postoperative outcomes, particularly in patients undergoing highly invasive pancreatic resection.

Patients with resectable pancreatic ductal adenocarcinoma who underwent pancreaticoduodenectomy as upfront surgery or after neoadjuvant chemotherapy with gemcitabine and S-1 between January 2015 and December 2022 were assessed. In addition to perioperative surgical outcomes, preoperative nutritional status was evaluated using serum albumin, controlling nutritional status, and prognostic nutritional index.

A total of 158 patients who underwent upfront pancreaticoduodenectomy and 119 who received neoadjuvant chemotherapy with gemcitabine and S-1 before pancreaticoduodenectomy were evaluated. Preoperative nutritional assessments (serum albumin, controlling nutritional status score, and prognostic nutritional index) showed no significant differences between groups, either at the initial consultation or immediately before surgery. No significant differences were observed in postoperative outcomes, including blood loss, operation time, and morbidity. The neoadjuvant chemotherapy with gemcitabine and S-1 group had a significantly greater rate of negative tumor margins (R0 resection rate 86% vs 74%, P = .018), and improved overall survival (hazard ratio, 0.41; 95% confidence interval, 0.25-0.67, P < .001) compared with the upfront pancreaticoduodenectomy group.

Neoadjuvant chemotherapy with gemcitabine and S-1 does not adversely impact preoperative nutritional status and enhances the effectiveness of pancreaticoduodenectomy for resectable pancreatic ductal adenocarcinoma, leading to improved pathologically curative resection rates and overall survival.

The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria. Our aim was to analyze the ESPAC4 survival on long-term follow-up.

The OS of 732 ESPAC4 patients comparing 367 randomly assigned to gemcitabine and 365 to GemCap was previously reported after a median follow-up time of 43.2 months (95% CI, 39.7 to 45.5) and 458 deaths. Analysis was now carried out after a median follow-up of 104 months (101-108) and 566 deaths.

The median OS was 29.5 months (27.5-32.1) for all patients, 28.4 months (25.2-32.0) in the gemcitabine group and 31.6 months (26.5-38.0) in the GemCap group (hazard ratio [HR], 0.83 [0.71 to 0.98]; P = .031). R0 patients given gemcitabine had a median survival of 32.2 months (27.9-41.6) compared with 49.9 months (39.0-82.3) for those given GemCap (HR, 0.63 [0.47 to 0.84]; P = .002). Lymph node-negative patients had significantly higher 5 year OS rates on GemCap (59% [49%-71%]) than gemcitabine (53% [42%-66%]; HR, 0.63 [0.41 to 0.98]; P = .04) but not those with positive lymph nodes (P = .225). The OS advantage for GemCap was retained in the PRODIGE24 subgroup of 193 (26.4%) ESPAC4 patients not eligible for PRODIGE24 with a median survival of 20.7 (16.2-27.3) months in patients allocated to gemcitabine compared with 25.9 (22.3-30.2) months for ineligible patients allocated to GemCap (HR, 0.71 [95% CI, 0.52 to 0.98]; χ2log-rank-1df = 4.31; P = .038).

GemCap is a standard option for patients not eligible for mFOLFIRINOX. Exploratory evidence suggests that GemCap may be particularly efficacious in R0 patients and also in lymph node-negative patients.

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.

Pancreatic pathology is a constant multidisciplinary challenge. It is a growing pathology and one of the main research topics. The aim of the study is to analyse the current situation in Spain in this field from a bibliometric perspective.

We conducted a systematic review following the PRISMA guidelines, utilizing the PubMed/Medline and sCIELO databases. The search strategy included the terms: '(pancreas OR pancreatectomy) AND surgery AND Spain.' The publication period spanned from January 2019 to March 2024. Our inclusion criteria specified any article, in any language, where at least one participant was a surgeon in a hospital in Spain, and that had an impact factor (IF).

The search yielded 522 citations, of which 133 articles were selected after applying our inclusion and exclusion criteria. The trend over time indicates a progressive increase in publications. Notably, 36.1% of the articles were published in Q1 journals, while 35.3% appeared in Q3 journals, with a mean impact factor of 4.07. Spanish authors accounted for 63.2% of publications. The most common types of articles were retrospective studies, case reports, and systematic reviews, with 35.3% being international multicenter studies. Key topics addressed included minimally invasive approaches, surgical techniques, and postoperative management. The journal Cirugía Española (Q3) published the highest number of papers (20.3%).

In recent years, Spain has experienced a significant increase in publications related to pancreatic surgery. However, when compared to leading countries in this field, the number of randomised clinical trials remains low.