Only 15% to 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have access to surgical resection, which represents the only chance of curative treatment. Current resection classifications are almost exclusively anatomic and do not correlate sufficiently with patient survival. It is essential to develop preoperative prognostic factors to distinguish patients at high risk of early postoperative recurrence from those who will have prolonged survival after surgery. In some cases, PDACs may present biomolecular differences reflecting their aggressiveness that are not yet assessable by the current clinical-biologic assessment. This study aimed to assess the preoperative prognostic factors that are already available and the future perspectives being developed.

This study reviewed the literature using the PubMed public database for preoperative prognostic factors for resectable PDAC.

Validated preoperative prognostic factors, whether clinical, biologic, radiologic, or histologic, are very important in anticipating the course of each patient's disease. The identification of potential new prognostic biomarkers such as genomic, transcriptomic, and proteomic analyses and the dosage of circulating tumor DNA are very serious avenues to be developed, but the extraction and analysis techniques as well as the interpretation of their results need to be standardized in prospective studies.

The benefits of palliative minimally invasive distal pancreatectomy for patients with unexpectedly metastatic pancreatic ductal adenocarcinoma have not been previously studied. This retrospective study compared the outcomes of palliative minimally invasive distal pancreatectomy with those of minimally invasive biopsy in these patients.

We reviewed the records of 46 patients with unexpected metastasis of left-sided pancreatic ductal adenocarcinoma that were discovered during surgery between 2005 and 2019. Nineteen patients underwent palliative resection (minimally invasive distal pancreatectomy group), whereas 27 patients underwent only minimally invasive biopsy (minimally invasive biopsy group). Demographic, clinical, and operative data, as well as survival rates, were compared between the 2 groups.

Major complications (Clavien-Dindo grade ≥3) were comparable between the 2 groups (11.8% vs 5.6%; P = .603). Postoperative chemotherapy was administered to 84.2% of the minimally invasive distal pancreatectomy group and 77.8% of the minimally invasive biopsy group (P = .716). The minimally invasive distal pancreatectomy group had a higher completion rate of first-line palliative chemotherapy (42.9% vs 8.7%; P = .007) and a higher 2-year survival rate (36.8% vs 18.8%; P = .004). In multivariate analysis, survival was associated with completion of first-line chemotherapy (hazard ratio: 2.962; P = .003) and maintenance chemotherapy for over 12 months (hazard ratio: 2.339; P = .010). Gastric outlet obstruction was less prevalent in the minimally invasive distal pancreatectomy group (5.3% vs 25.9%, P = .037).

Palliative minimally invasive distal pancreatectomy may improve survival and facilitate the continuation of chemotherapy in selected patients with unexpected metastatic pancreatic ductal adenocarcinoma. However, the small sample size and potential selection bias limit the generalizability of these findings. Larger, prospective, multicenter studies are needed to confirm the role of minimally invasive distal pancreatectomy and to establish optimal management strategies for these patients.

This study aims to evaluate the effectiveness of contrast-enhanced computed tomography (CT) in distinguishing non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with a normal serum level of carbohydrate antigen 19-9 (CA19-9) levels.

This retrospective study included 134 patients with pathologically confirmed non-hypervascular PNENs and 128 patients with CA19-9-negative PDACs, all of whom underwent contrast-enhanced CT prior to surgery between January 2015 and March 2024. Following independent evaluation by two radiologists, qualitative features from both groups were extracted in the arterial and portal venous phase and subsequently compared using univariate and multivariate analysis.

Patients with CA19-9 negative PDACs were significantly older than those with non-hypervascular PNENs (p < 0.001), and the majority of PDACs were located in the head of the pancreas (p < 0.01).Univariate analysis showed that non-hypervascular PNENs exhibited a higher frequency of well-defined tumor margins (p < 0.001) and calcification (p = 0.032) and a lower frequency of local invasion (p < 0.001), peripancreatic vascular invasion (p = 0.001), intra- or extrahepatic bile duct dilatation (p < 0.001), distal main pancreatic duct dilatation (p < 0.001), regional lymphadenopathy (p < 0.001) and tumor homogeneity (p < 0.001) when compared to CA19-9 negative PDACs. Multivariate analysis identified the absence of local invasion (Odds Ratio (OR) = 0.233; 95 % Confidence Internals (95 % CI):0.114-0.476; p < 0.001), absence of peripancreatic vascular invasion (OR = 0.434; 95 % CI:0.217-0.870; p = 0.019), a normal distal main pancreatic duct diameter (OR = 0.398; 95 % CI:0.202-0.785; p = 0.008), absence of regional lymphadenopathy (OR = 0.455; 95 % CI:0.238-0.870; p = 0.017) and tumor heterogeneity (OR = 0.240; 95 % CI:0.126-0.456; p < 0.001) as significant predictors of non-hypervascular PNENs. The area under the receiver operating characteristic curve for the radiological feature model was 0.829 based on logistic regression.

Qualitative features in contrast-enhanced CT images could be beneficial in differentially diagnosing non-hypervascular PNENs and CA19-9 negative PDACs.

The prognostic value of serial 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) for patients with borderline resectable or locally advanced pancreatic cancer who undergo conversion surgery or continue chemotherapy without surgery has not been well-established.

A retrospective analysis of patients with pancreatic ductal adenocarcinoma was conducted at Seoul National University Bundang Hospital between March 2013 and February 2022. Patients underwent PET/CT at baseline and subsequent radiologic evaluations following chemotherapy. Changes in the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume, and total lesion glycolysis were analyzed. Based on their treatment regimens, patients were stratified into the conversion surgery group or nonconversion surgery group. Survival outcomes and various clinical factors were assessed.

Among 121 patients, 52 underwent conversion surgery, and 69 continued to receive chemotherapy without surgery. A significant reduction in the SUVmax was correlated with prolonged recurrence-free survival and overall survival in the conversion surgery group. Confirmation of a pathologic response indicated a significant association between reductions in the SUVmax and positive outcomes. Reductions in the metabolic tumor volume and total lesion glycolysis were associated with improved progression-free survival and overall survival in the nonconversion surgery group.

Serial PET/CT scans demonstrated prognostic value in pancreatic ductal adenocarcinoma patients, revealing distinct correlations in the conversion surgery group and nonconversion surgery group.

The clinical relevance of high-grade pancreatic intraepithelial neoplasia (PanIN) at the pancreatic transection margin (PTM) during resection of pancreatic ductal adenocarcinoma (PDAC) remains unclear.

A total of 358 patients who underwent R0 resection for PDAC between January 2010 and December 2022 were included. The permanent sections used for the intraoperative frozen section diagnosis of PTM were evaluated for the PanIN grade.

Among 358 patients, 35 patients had low-grade PanIN (9.8%), and 17 had high-grade PanIN (4.7%) at the PTM. The 2-year overall survival (OS), disease-free survival (DSS), and relapse-free survival (RFS) did not differ markedly among patients with normal epithelium, low-grade PanIN, or high-grade PanIN at the margin. As the clinical features differed between patients with high-grade PanIN at the PTM and those without, we adjusted the patients' background factors using propensity score matching. The 2-year OS, DSS, and RFS rates were not significantly different between the groups. In addition, we investigated the details of 17 cases of high-grade PanIN in the PTM. The analysis revealed that 11 patients experienced recurrence after surgery. Among them, two cases of T1N0 showed recurrence in the remnant pancreas more than 2 years after surgery, while nine cases exhibited recurrence outside the remnant pancreas, such as the liver and lungs, within 2 years.

Patients with high-grade PanIN at the PTM did not show a significantly different prognosis than those without; however, recurrence in the remnant pancreas was observed in long-term survivors. Therefore, rigorous long-term follow-up is essential for such patients.

The use of 10-mm fully covered self-expandable metal stents for preoperative bile duct drainage in patients with pancreatic cancer is increasing. However, these can cause complications (cholecystitis and pancreatitis) that may affect surgical outcomes. Smaller-diameter self-expandable metal stents may reduce these risks; however, the optimal stent size is unclear.

Patients with pancreatic cancer who underwent neoadjuvant chemotherapy and placement of either 6 or 10-mm fully covered self-expandable metal stents for malignant distal biliary obstruction were included. The primary outcome was the 90-day incidence of recurrent biliary obstruction. Secondary outcomes were non-recurrent biliary obstruction and adverse events.

Fifty-three patients were enrolled (27 and 26 patients received 6-mm and 10-mm self-expandable metal stents, respectively). The 90-day incidence of recurrent biliary obstruction of the 6-mm group was significantly higher than that of the 10-mm group (30.8% vs. 3.8%; p = 0.02). Stent migration occurred more frequently in the 6-mm group (26.9% vs. 0%; p = 0.01). Although non-recurrent biliary obstruction adverse events were less common in the 6-mm group, the difference was not statistically significant (11.1% vs. 23.0%; p = 0.29).

The 10-mm self-expandable metal stents were more suitable for the preoperative management of pancreatic cancer.

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.

Complete oncological local control is essential for a potential cure in patients with pancreatic ductal adenocarcinoma (PDAC), but predicting local recurrence following curative surgery remains clinically challenging. In this study, we performed comprehensive biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) following curative surgery in patients with PDAC.

To identify axon guidance-related microRNAs, we performed the pathway-miRNA interaction analysis using the miRPathDB2.0. Subsequently, the predictive performance of the miRNAs was trained and validated in three independent clinical surgically resected sample cohorts and one pretreatment blood sample cohort with different disease statuses [upfront surgery cohort: n = 162 (training: n = 103, internal validation: n = 59), neoadjuvant chemoradiotherapy (NACRT) cohort: n = 217, arterial invasion cohort: n = 62, pretreatment blood sample cohort: n = 53].

The pathway-miRNA interaction analysis identified 13 miRNAs related to axon guidance pathway. Subsequently, we trained a 13-miRNA risk-prediction model, AGMP, which robustly distinguished PPR after surgery in the training cohort (AUC = 0.95). The AGMP was successfully validated in three independent cohorts (AUC: validation = 0.94, NACRT = 0.94, Arterial invasion = 0.90). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort, which again confirmed the robustness of risk-stratification for PPR (AUC = 0.86).

We developed a novel biomarker, AGMP that demonstrated remarkable predictive performance for PPR following curative surgery in patients with PDAC; highlighting the clinical importance of the nerve-cancer cross-talk and the hopefulness as a guidepost for designing future clinical and basic research to establish individualized treatment strategies.

A leaking pancreaticojejunal anastomosis is typically the cause of major problems following pancreaticoduodenectomy. To stop fistula formation, omental flaps were positioned around the pancreaticojejunal anastomosis.

Forty-eight individuals who had pancreaticoduodenectomy procedures performed between March 2022 and March 2024 were examined. Based on the placement of a stent and omental flaps around the pancreaticojejunal anastomosis, the patients were split into two groups: group A, consisting of twenty-four patients, did not get omental wrapping and stenting, and group B, consisting of twenty-four patients, received omental wrapping with stent inside the pancreaticojejunal anastomosis. To evaluate the efficacy of the omental flap operation in preventing postoperative pancreatic fistula and other complications, perioperative data from both groups was examined.

There were no discernible variations in the clinical traits of the two groups. Group B experienced considerably lower occurrences of postoperative pancreatic fistula (20.8% vs. 4.2%), post-pancreatectomy hemorrhage (4.2% vs. 0%), biliary fistula (4.2% vs. 0%), and delayed gastric emptying (12.5% vs. 4.2%). Group B had a considerably lower overall morbidity rate (41.7% vs. 8.3%) and shorter hospital stay (15.3 vs. 10.9 days) than to group A.

Following pancreaticoduodenectomy, pancreatic stent and omental flaps around the pancreatic anastomosis can lower the risk of postoperative pancreatic fistula, post-pancrectomy bleeding, and delayed gastric emptying. This straightforward and efficient treatment can decrease the overall morbidity following pancreaticoduodenectomy.

The trial registration was recorded as ClinicalTrial.gov Identifier No.: NCT06630910 on 10/05/2024. Our study also adheres to the Declaration of Helsinki.

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.

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.

The potential long-term survival benefits of surgical resection for synchronous liver-only metastases of pancreatic ductal adenocarcinoma (liver oligo-PDAC) remain controversial. This systematic review and meta-analysis aim to compare the current evidence on long-term survival outcomes between surgical treatment of liver oligo-PDAC and conventional systemic chemotherapy.

A systematic review and meta-analysis were conducted using the PubMed and Scopus databases to identify studies comparing surgery and systemic chemotherapy in terms of long-term survival in oligo-PDAC patients. The search included studies published up to October 2024. The meta-analysis was performed using the Jamovi software.

Eleven retrospective studies were selected for a total of 897 patients: 565(63%) underwent synchronous resection of liver metastases and the primary tumor, while 332(37%) received conventional chemotherapy. The majority of patients presented a pancreatic head tumor, and the median number of liver metastases ranged between 1 and 3 in the surgical cohort and 1 and 2 in the nonsurgical cohort. The rate of major surgical complications was 14.4% while the cumulative incidence of postoperative mortality was 2.8%. The median overall survival(OS) in the surgical group ranged from 7.6 to 18.4 months, while a lower value comprised between 6 and 9.9 months was evidenced in the nonsurgical cohort. Six studies were included in the meta-analysis for the OS evaluation, showing significantly better survival outcomes in the surgical group (OR: 0.286, 95% CI: 0.100-0.409; P < 0.0001). According to the Q-test, there was no significant heterogeneity in the true outcomes ( Q = 4.063, P = 0.541, I2  = 0 %). A sensitivity analysis, conducted by excluding one study at a time, confirmed the robustness of the meta-analysis findings.

Surgical resection of oligo-PDAC may represent a valuable treatment option with potential long-term survival benefits. However, prospective randomized trials are required to further validate these findings.

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.

To compare perioperative morbidity and mortality in patients receiving pancreatoduodenectomy or total pancreatectomy for pancreatic head adenocarcinoma using German Cancer Registry data.

Anonymized pooled data were retrieved from regional cancer registries participating in the German Cancer Registry Group of the Association of German Tumor Centers. Included were patients diagnosed with pancreatic head adenocarcinoma since 2016, receiving curative intent pancreatoduodenectomy or total pancreatectomy. Patients were propensity-score matched according to age, sex, and histopathology. Primary endpoints were 30- and 90-day postoperative mortality. Secondary endpoints were administration of adjuvant chemotherapy, long-term survival, and patterns of cancer recurrence. The data were analyzed using R.

In total, 756 patients per treatment group were matched for further analyses. R0-resection rate was comparable between pancreatoduodenectomy and total pancreatectomy (69.6 vs 73.4%, P = .154). The 30-day (9.5 vs 4.8%, P < .001) and 90-day postoperative mortality (18.0 vs 11.0%, P < .001) rates were significantly lower after pancreatoduodenectomy compared with total pancreatectomy. After pancreatoduodenectomy, more patients received adjuvant chemotherapy (43.6 vs 53.3%, P < .001) and time to adjuvant chemotherapy was shorter (60.1 vs 52.7 days, P = .002) compared with total pancreatectomy. Long-term overall survival was worse after total pancreatectomy (P < .001), also in patients receiving adjuvant chemotherapy (P = .019). The sites of recurrence were comparable between both groups (P = .274).

The results of this study show greater perioperative morbidity and mortality after total pancreatectomy compared with pancreatoduodenectomy for pancreatic head malignancy. Also, long-term survival was worse after total pancreatectomy. These results emphasize the role of pancreatoduodenectomy as a standard surgical procedure for pancreatic head adenocarcinoma and suggest that total pancreatectomy should only be performed in selected patients.

Laparoscopic pancreatic surgery remains highly challenging due to the complexity of the pancreas and surrounding vascular structures, with risk of injuring critical blood vessels such as the Superior Mesenteric Vein (SMV)-Portal Vein (PV) axis and splenic vein. Here, we evaluated the High Resolution Network (HRNet)-Full Convolutional Network (FCN) model for its ability to accurately identify vascular contours and improve surgical safety. Using 12,694 images from 126 laparoscopic distal pancreatectomy (LDP) videos and 35,986 images from 138 Whipple procedure videos, the model demonstrated robust performance, achieving a mean Dice coefficient of 0.754, a recall of 85.00%, and a precision of 91.10%. By combining datasets from LDP and Whipple procedures, the model showed strong generalization across different surgical contexts and achieved real-time processing speeds of 11 frames per second during surgery process. These findings highlight HRNet-FCN's potential to recognize anatomical landmarks, enhance surgical precision, reduce complications, and improve laparoscopic pancreatic outcomes.

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.

Complete oncological resection of pancreatic cancer remains the cornerstone in treatment of pancreatic cancer. Anatomical relations to major vessels continue to play an ongoing important role in the decision-making regarding treatment options in pancreatic cancer. Despite concomitant venous resections being routinely performed in major centers, arterial resections remain controversial. The aim of this study was to compare the short- and long-term outcomes of pancreatic cancer surgery with concomitant arterial resections to standard non-arterial resections from modern studies. We included studies comparing pancreatic cancer surgery with arterial resections to standard non-arterial surgery for pancreatic cancer published from 2018 to 2024. A total of seven articles involving 5465 patients met the inclusion criteria and were included for analysis. Arterial resections are associated with a greater risk of mortality compared to standard resections (Risk ratio (RR): 3.28; 95% confidence interval (CI) [0.75-14.46]; p = 0.0365). There were no significant differences in overall morbidity (RR: 1.48; 95% CI [1.16-1.89]; p = 0.2923) or serious complications (Mean Difference (MD): 2.6; 95% CI: [-21.52-16.32]; p = 0.738). Arterial resections were associated with a 3.1-fold increased chance of R0 resection (RR: 3.11; 95% CI [1.65-5.86]; p < 0.0227). Arterial resection in pancreatic cancer continues to be associated with an increased risk of mortality; however, recent studies show no significant increase in morbidity whilst significantly increasing R0 resections.

Metastatic PDAC has a very poor prognosis, and surgery has a limited role. The study aims to evaluate the OS of patients with PDAC and synchronous liver metastasis who undergo surgical therapy (ST) versus non-surgical therapies (NST).

We performed a random effects meta-analysis. Inclusion criteria were: PDAC histology; studies reporting technically resectable cases with liver metastasis and survival data; absence of extra-hepatic disease. The primary endpoint was to evaluate OS. Results were reported as HR and 95 % CI. We performed a meta-regression analysis to identify factors influencing heterogeneity. We analyzed key covariates in order to predict how changes in these factors affect HR.

Six studies were included. The OS was significantly better in group ST than NST, with HR = 0.41 (95 % CI: 0.32-0.52). Heterogeneity was high (I2 = 64.50 %). As the rate of patients who underwent postoperative CT in the ST group decreased, the difference between the two groups decreased (β = -1.28 ± 0.67; p = 0.003), with almost 87.10 % heterogeneity. The adjusted effect based on meta-regression showed an improved OS in ST group only when both pre- and post-operative systemic CT were administrated (HR 0.18, 95 % CI: 0.08-0.40).

In highly selected patients with metastatic PDAC who respond to systemic CT and receive post-operative systemic CT, ST could be associated with improved OS. However, the high heterogeneity and retrospective design of included studies limit the ability to draw definitive conclusions.

To evaluate the feasibility of implementation of structured reporting in the setting of a high-volume pancreatic multidisciplinary clinic (PMDC) and to assess its value by comparing the accuracy of structured reports with expert imaging reviews.

A single institutional prospective cohort study was conducted during March 2022 to May 2024 to understand the feasibility of implementation of structured reporting (SR) for all patients who were seen in our weekly PMDC. Descriptive and regression analyses were performed to find an association between SR and difference in vascular involvement of the primary pancreatic tumor between the radiology report and expert radiologist review (gold standard) during PMDC.

Among 466 patients seen in the PMDC, 426 (91.4%) had reports generated prior to PMDC. Of this, 294 reports met the inclusion criteria. The usage of SR increased from 58.3% in Mar 2022 to 87.8% in June 2024. Majority of the reports that used SR (n = 226, 76.9%), were performed for initial staging (n = 197, 67.0%) of PC. The median years of experience of reading radiologists that used non-SR was 14 (IQR: 8-27) years, while it was 9 (IQR - 9-15) years for those who used SR (p = 0.030). Of note, as compared to the radiology report, increased vascular involvement was noted in PMDC review 62.5% (20 out of 32) of the time with non-SRs, whereas increased vascular involvement during PMDC review was noted in only 36.6% (48 out of 132) of the time with SRs. On multivariable analysis, using SR lowered the odds of increase in vascular involvement during PMDC review by 0.29 times (95CIs 0.11-0.79; p = 0.015).

SR is feasible and superior to the free-text reporting with respect to the accuracy of peri-pancreatic vascular involvement. While its use cannot replace the PMDC radiology review, it can nonetheless be an indispensable tool in clinical management, particularly in a non-PMDC setting.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Approximately 10% of affected individuals have an inherited component. Deleterious germline variants increase the lifetime risk for PDAC and are often associated with an elevated risk for extra-pancreatic malignancies. In this study, we aimed to determine the prevalence and impact of germline pathogenic variants (gPVs) in patients with PDAC and extra-pancreatic malignancies. Using tissue samples and longitudinal data from a nationwide pathology database, we identified patients with PDAC and a set of 7 extra-pancreatic malignancies to investigate the presence of gPVs in 25 cancer susceptibility genes with targeted next-generation sequencing. Of 473 patients with PDAC and at least 1 extra-pancreatic malignancy, 75 (16%) had gPVs. These were predominantly in ATM (n = 22), CDKN2A (n = 14), BRCA2 (n = 10), or CHEK2 (n = 10) genes. The combination of PDAC and ovarian carcinoma carried the highest prevalence of gPVs (4 of 10; 40%), followed by PDAC and melanoma (15 of 53; 28%), and PDAC and gastric cancer (2 of 9; 22%). Patients with PDAC and certain extra-pancreatic malignancies carry a higher burden of gPVs than unselected PDAC cohorts. This is a group that very likely benefits from genetic testing because germline status can have important diagnostic and therapeutic implications for affected individuals and their family members.

Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits an immunosuppressive microenvironment coupled with malnutrition status. These features are instrumental in clinical management strategies for PDAC.

Immune-nutrition status of patients was evaluated by integrating systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI). Individuals were divided into SII-PNI Status positive (SPS+) group and SPS negative (SPS-) group. Morphology of tissues was evaluated by hematoxylin-eosin (H&E) staining. Expression of PD-L1 and p53 was detected using immunohistochemistry (IHC).

In this study, 530 eligible patients (mean ± SD age, 60.5 ± 9.17 years, 296 males [55.8%], 74 SPS+ [14.0%]) were included. These patients exhibited a median survival of 24 months (1-, 3- and 5-year survival rate; 72.9%, 34.7% and 25.1%, respectively). In the multivariate analysis, independent indicators for outcomes were identified as tumor size, lymph node metastasis and SPS (all p <.01). After matching and adjusting, patients with SPS+ exhibited a notably reduced overall survival compared to those with SPS- (14 vs. 25 months, p <.001), with hazard ratio (95% CI) of 1.79 (1.25-2.56). IHC revealed markedly elevated positive cell proportion of PD-L1 in SPS+ group (p <.01) and distinct p53 mutation patterns between SPS+ and SPS- groups (p =.03). Morphology demonstrated a dissimilar trend of differentiation levels between the two groups (p =.08).

The findings suggest poorer outcome, higher PD-L1 expression and distinct p53 mutation status of patients with SPS+. These patterns may contribute to PDAC management and strategic deployment of immunotherapy and targeted therapy.

Pancreatic cancer is characterised by its aggressive progression, late-stage diagnosis and poor prognosis. This case report illustrates the intricate interplay between pancreatic adenocarcinoma, disseminated intravascular coagulation with diffuse alveolar haemorrhage and bone metastasis in an elderly woman. Presenting with asthenia, significant hip pain and haemoptysis, her work-up revealed multiple supradiaphragmatic adenopathies and infradiaphragmatic adenopathies, pancreatic parenchymal heterogeneity and lytic bone lesions. Despite extensive diagnostic efforts, a diagnosis of adenocarcinoma of probable pancreatobiliary origin was established only at an advanced stage, leading to a fatal outcome within a week. The patient experienced rapid clinical deterioration, characterised by refractory respiratory failure, haematological dysfunction and circulatory shock, highlighting the aggressive course of pancreatic cancer and its complications. This case underscores the diagnostic challenges and the critical need for early recognition and tailored strategies in managing complex presentations of pancreatic cancer, especially with rare and severe systemic manifestations.

Ampullary adenocarcinomas are a rare disease. They can be classified anatomically or according to their histology into intestinal, pancreatobiliary, and mixed subtypes, with different subtypes having distinct prognoses and potential treatments. We report a clinical case of a patient with mixed type adenocarcinoma of the ampulla of Vater, with predominantly intestinal histology, associated with an isolated and synchronous peritoneal carcinomatosis. It is the only case reported in the literature of duodenal ampulla cancer with synchronous peritoneal metastases, with long-term survival.

A 53-year-old male patient with non-insulin-dependent diabetes presented with acute abdominal pain in the right hypochondrium. Images revealed dilatation of the biliary tract and the duct of Wirsung, without a clear obstructive factor. Upper gastrointestinal endoscopy revealed a tumor in the duodenal papilla. Biopsies confirmed an adenocarcinoma. In the first surgical step, a biliodigestive bypass was performed in association with resection of the carcinomatosis. Peritoneal metastases was found during the intraoperative period. Subsequently, chemotherapy with the folinic acid, fluorouracil, and oxaliplatin regimen was administered based on histology, and a favorable response was achieved. After a multidisciplinary discussion, the Whipple procedure was performed. A delayed biopsy showed disease-free margins. The patient achieved 5 years of overall survival in August 2024, and 4 years of disease-free survival in September 2024.

We conclude that an important value of this work is showing individualized treatment for a patient with cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor. Surgical resection is the most promising therapeutic strategy for PDAC, and how to improve the survival rate remains a vital key point. This study aimed to establish and validate a nomogram for predicting the prognosis of resected PDAC.

A total of 174 patients with PDAC who underwent surgical resection at Lanzhou University Second Hospital and the First Affiliated Hospital of Zhengzhou University from January 2012 to July 2022 were enrolled. The clinicopathological characteristics and survival data were analyzed by R software (version 4.1.3). Univariate and multivariate Cox regression analyses were used to analyze the effects of clinicopathological characteristics on overall survival (OS).

Multivariate Cox regression showed that carbohydrate antigen 19-9 (CA19-9) ≥ 476 U/mL, carbohydrate antigen 125 (CA125) ≥ 32 U/mL, fasting blood glucose (FBG) < 6.86 mmol/L, aspartate aminotransferase (AST) ≥ 107 U/L, positive surgical margin, and more than 4 cycles of postoperative chemotherapy were independent prognostic factors for OS. Patients were divided into the high-risk and low-risk groups based on the median risk score calculated by multivariate Cox regression analysis. Kaplan-Meier survival curves revealed that the 5-year survival rates of the high-risk and low-risk groups in the training cohort were 5.79% and 24.3%, respectively, and those in the validation cohort were 0 and 19.0%, respectively (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that area under the ROC curve (AUC) of the risk score in the training set and the validation set were 0.855 and 0.838, respectively. The C-indexes of the nomogram in the training set and validation set were 0.788 (95% CI: 0.745-0.831) and 0.773 (95% CI: 0.718-0.828), respectively.

We developed a nomogram that predicts OS in patients with resected PDAC, and the validation results showed that the nomogram model had a strong predictive ability. Particularly, FBG < 6.86 mmol/L and more than 4 cycles of postoperative chemotherapy can predict better OS of PDAC after surgery.

Extracellular vesicles (EVs) are celebrated for their pivotal roles in cellular communication and their potential in disease diagnosis and therapeutic applications. However, their inherent heterogeneity acts as a double-edged sword, complicating the isolation of specific EV subpopulations. Conventional EV isolation methods often fall short, relying on biophysical properties, while affinity-based techniques may compromise EV integrity and utility with harsh recovery conditions. To address these limitations, the SHINER (subpopulation homogeneous isolation and nondestructive EV release) workflow is introduced, which redefines how EVs are isolated and recoverd, featuring the innovative SWITCHER (switchable extracellular vesicle releaser) tool. The SHINER workflow facilitates the precise purification and gentle recovery of target EV subpopulations from complex biological mixtures, preserving their structural integrity and biological functionality. Importantly, SHINER demonstrates exceptional adaptability to multiple markers and clinical applications. It not only enhances the ability to trace EV origins for accurate disease diagnosis but also advances fundamental EV research and provides standardized EV materials for therapeutic innovations. By improving the understanding of EVs and enabling the development of personalized diagnostics and treatments, SHINER propels EV-based science into new frontiers of advanced medicine, offering transformative potential for healthcare.

Pancreatic fistula is the most common complication of pancreatic surgeries that causes more serious conditions, including bleeding due to visceral vessel erosion and peritonitis.

To develop a machine learning (ML) model for postoperative pancreatic fistula and identify significant risk factors of the complication.

A single-center retrospective clinical study was conducted which included 150 patients, who underwent pancreatoduodenectomy. Logistic regression, random forest, and CatBoost were employed for modeling the biochemical leak (symptomless fistula) and fistula grade B/C (clinically significant complication). The performance was estimated by receiver operating characteristic (ROC) area under the curve (AUC) after 5-fold cross-validation (20% testing and 80% training data). The risk factors were evaluated with the most accurate algorithm, based on the parameter "Importance" (Im), and Kendall correlation, P < 0.05.

The CatBoost algorithm was the most accurate with an AUC of 74%-86%. The study provided results of ML-based modeling and algorithm selection for pancreatic fistula prediction and risk factor evaluation. From 14 parameters we selected the main pre- and intraoperative prognostic factors of all the fistulas: Tumor vascular invasion (Im = 24.8%), age (Im = 18.6%), and body mass index (Im = 16.4%), AUC = 74%. The ML model showed that biochemical leak, blood and drain amylase level (Im = 21.6% and 16.4%), and blood leukocytes (Im = 11.2%) were crucial predictors for subsequent fistula B/C, AUC = 86%. Surgical techniques, morphology, and pancreatic duct diameter less than 3 mm were insignificant (Im < 5% and no correlations detected). The results were confirmed by correlation analysis.

This study highlights the key predictors of postoperative pancreatic fistula and establishes a robust ML-based model for individualized risk prediction. These findings contribute to the advancement of personalized perioperative care and may guide targeted preventive strategies.

Weight loss and exocrine pancreatic insufficiency are common in advanced pancreatic ductal adenocarcinoma (PDAC) and are associated with adverse outcomes. However, there is limited evidence on the impact of pancreatic enzyme replacement therapy (PERT) in patients with advanced PDAC.

We retrospectively studied 501 patients with advanced PDAC and exocrine pancreatic insufficiency from the Virginia Mason Pancreas Cancer Program Data Resource treated between 2010 and 2019 with first-line chemotherapy. Clinical outcomes were compared between those who received PERT and those who did not at 8 weeks after chemotherapy start.

In total 188 (38%) patients received PERT; 313 patients (62%) did not. PERT patients experienced less weight loss (-1.5 vs -2.5 kg, P = .04), less decline in the prognostic nutrition index -1.9 vs -3.0, P = .01), and a greater reduction in the additive score of the Patient-Generated Subjective Global Assessment (-8.4 vs --6.0, P = .02). Importantly, median (95% CI) overall survival (OS) was significantly longer in the PERT vs non-PERT group (17.1 months vs 12.5 months, respectively P = .001), and the adjusted hazards ratio indicated superior median OS in patients prescribed PERT (HR = 0.73, P < .001).

Our findings suggest that treatment of exocrine pancreatic insufficiency (EPI) in advanced PDAC is associated with improvements in nutrition and overall survival.

Celiac plexus stereotactic body radiation therapy (CP-SBRT) using 25 Gy in a single fraction is an effective method of palliative pain relief for patients suffering from celiac axis tumor invasion. Standard complex stereotactic body radiation therapy workflows for simulation and planning result in delays in pain relief during end-of-life care. We propose a simulation-free, direct-to-unit (DTU) adaptive radiation therapy (ART) approach, using a diagnostic computed tomography (CT) preplan and online adaptation for final plan construction to enable the same-day radiation oncology consult and CP-SBRT. We aimed to demonstrate that this advanced imaging has increased electron density accuracy which enables the test of this DTU, adaptive CP-SBRT workflow in silico.

Ten patients with abdominal malignancies were imaged on a HyperSight Cone Beam Computed Tomography (CBCT) solution on a C-arm linear accelerator as part of a prospective imaging clinical trial (NCT05975619). These patients' existing diagnostic CT scans were used to generate CP-SBRT preplans. To simulate a simulation-free, DTU workflow, HyperSight CBCT images were injected into a CT guided ART treatment planning system environment as the primary data set, with target contours propagated from the registered diagnostic CT. Contours were updated as needed to reflect the treatment anatomy and positioning. A standard online ART workflow was used for the predicted and final adaptive plan calculation. Dose-volume values for each clinical goal were compared between predicted and final plans. Timing and measured quality assurance data were also collected.

DTU adaptive CP-SBRT plans were successfully created for all 10 patients and met all clinical goals. Without adaptation, predicted plans were infeasible for clinical use; 9 of 10 patients had nondeliverable predicted plans. The average time to complete ART contouring was 6 minutes. The average gamma passing rate for 3%/2 mm was 92.6%.

DTU ART for CP-SBRT is dosimetrically feasible. Adaptation is a critical component for DTU CP-SBRT to achieve deliverable plans. This approach could reduce treatment delay for cancer-related celiac pain.