Histopathological stage I pancreatic cancer (PC) consists of four entities according to the Union for International Cancer Control (UICC) 8th staging system: pStage IA (cases underwent up-front surgery, pT1 [tumor size ≤20 mm] pN0), pStage IB (cases underwent up-front surgery, pT2 [20 mm < tumor size ≤40 mm] pN0), ypStage IA and IB (i.e., underwent neoadjuvant treatment [NAT]). This study aimed to evaluate surgical outcomes in patients with histopathological stage I PC ((y)pStage I).

Patients with PC who underwent resection and were diagnosed with (y)pStage I were included in this study (n = 121). We evaluated and compared recurrence-free survival (RFS) and overall survival (OS) among these four categories: pStage I vs. ypStage I, (y)pStage IA vs. IB, ypStage IA vs. IB, and pStage IA vs. IB.

There was no difference in the prognosis between pStage I and ypStage I cases, even though ypStage I included more advanced cases at NAT initiation. For pStage I (n = 25), no differences in prognosis were noted between pStage IA and IB (median RFS, 24 vs. 21 months, p = 0.871; median OS, 49.5 vs. 35.5 months, p = 0.213). However, in the ypStage I cohort (n = 96), there was significantly better RFS in ypStage IA (median RFS, 42 vs. 14 months, p = 0.0114; median OS, 52 vs. 36 months, p = 0.250).

Survival was comparable between pStage I and ypStage I cohorts, although the subcategories within each cohort (IA vs. IB) had different clinicopathological characteristics and outcomes.

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.

Tumor size (TS) in pancreatic ductal adenocarcinoma (PDAC) is one of the most important prognostic factors. However, discrepancies between TS on preoperative images (TSi) and pathological specimens (TSp) have been reported. This study aims to evaluate the factors associated with the differences between TSi and TSp.

We retrospectively analyzed patients with PDAC who underwent surgery at our institution between January 2010 and November 2023. TS discrepancy (TSD[%]) was defined as ([TSp - TSi]/TSp) × 100. Using logistic regression, we generated a receiver operating characteristic (ROC) curve to define the cutoff for TSi underestimation predicting clinical tumor (T) stage migration. Univariate and multivariate analyses were performed to evaluate predictors of TSi underestimation.

Of the 231 patients, 99 (42%) patients received preoperative chemotherapy. The ROC curve determined a TSD underestimation cutoff of 25.9%. The number of TSp > TSi cases was 185 (80%), and TSi underestimation was present in 117 (51%) patients. T stage migration rates were 76%, 26%, and 50% in clinical stage (c) T1, cT2, cT3, respectively, among the patients with chemotherapy, and 93%, 33%, and 14%, respectively, in those without chemotherapy. Multivariate analyses revealed that independent predictors of TSi underestimation were posterior surface invasion in the patients with preoperative chemotherapy and anterior surface invasion in those without chemotherapy.

TS was more commonly underestimated than overestimated, and cT1 rarely corresponded to pathological (p)T1. The factors contributing to TSi underestimation differed between patients with and without preoperative chemotherapy. Therefore, these two groups should be considered separately for accurate TSi evaluation.

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.

Pancreatic cancer (PC) is an aggressive and lethal tumor with a poor prognosis. FOLFIRINOX improves the prognosis of patients with PC; however, despite UGT1A1 screening, adverse events, such as severe neutropenia, occur frequently. This study aimed to identify the novel biomarkers of severe neutropenia in patients treated with modified FOLFIRINOX (mFFX) for PC. In this study, patients with PC treated with mFFX (n = 71) and gemcitabine plus nab-paclitaxel (GnP) (n = 92) and patients with colorectal cancer treated with FOLFOXIRI (n = 50) were included. Genome-wide screening using whole-exome sequencing was performed during the screening phase. Validation analysis was performed using polymerase chain reaction genotyping, the Cochran-Armitage trend test, and multivariate analysis. The diagnostic performance of combined risk factors for severe neutropenia was examined using logistic regression with leave-one-out cross-validation. Three gene polymorphisms were selected from the screening phase and subjected to the validation phase. In the validation phase, a single nucleotide polymorphism in C11orf24 (c.448C>T, rs901827) was significantly correlated with ≥ Grade 3 neutropenia in mFFX and FOLFOXIRI but not in GnP. Multivariate analysis showed C11orf24 and baseline neutrophil count as independent risk factors for ≥ Grade 3 neutropenia. The diagnostic performance of the neutropenia prediction model showed areas under the curve of 0.754 (sensitivity = 0.605, specificity = 0.848) and 0.856 (sensitivity = 0.800, specificity = 0.893) for ≥ Grade 3 and 4 neutropenia, respectively. The C11orf24 gene and baseline neutrophil count may be useful biomarkers for predicting severe neutropenia following irinotecan-containing triplet chemotherapy.

The standard adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) in Japan is S-1; however, the impact of dose reduction on prognosis remains unclear. We have reported that total dose intensity (TDI) ≥ 62.5% indicates good prognosis. This multicenter retrospective study evaluated the prognostic impact of TDI ≥ 62.5% and reduced dosing in patients who underwent radical resection for PDAC across three institutions.

Patients were grouped into high-TDI (≥ 62.5%) and low-TDI (< 62.5%) based on this cutoff. We performed an inverse probability of treatment weighting (IPTW)-adjusted analysis and calculated relapse-free survival (RFS) and overall survival (OS). OS was also calculated for high TDI with TDI < 100% and TDI = 100%.

Among 487 patients, 274 were included: 152 in the low-TDI and 122 in high-TDI groups. Patient background was adjusted using IPTW based on factors that might influence TDI. The median RFS for low- and high-TDI was 8 and 18 months, respectively (p = 0.004). The median OS of low- and high-TDI groups was 20 and 50 months, respectively (p < 0.001). Among patients with high TDI, OS did not differ between those with TDI < 100% and those with TDI = 100% (median, 47 vs. 72 months, p = 0.208).

It has been suggested that a partial dose reduction of S-1 as adjuvant chemotherapy for PDAC does not significantly impact prognosis.

Liposomal irinotecan + fluorouracil/leucovorin (nal-IRI + 5FU/LV) is commonly used as a second- or later-line treatment for pancreatic ductal adenocarcinoma (PDAC) and offers survival benefits. However, its efficacy and safety in patients previously treated with FOLFIRINOX, which includes irinotecan, remain unclear. We evaluated the efficacy and safety of nal-IRI + 5FU/LV in patients with unresectable PDAC who received previous FOLFIRINOX therapy and those who did not.

This retrospective observational study included 42 patients with PDAC who were treated with nal-IRI + 5FU/LV (October 2020-November 2023). Patients were grouped based on prior FOLFIRINOX treatment.

The progression-free survival (PFS) in patients who previously received modified FOLFIRINOX (mFFX) therapy was shorter than that in patients who did not (2.5 vs. 3.5 months, P = 0.07). When patients with greater than- and less than the cut-off value of irinotecan-free interval (IFI) were classified into the long and short IFI groups, respectively, PFS was significantly longer in the long-IFI group than that in the short IFI group (4.0 vs. 2.1 months, P = 0.01). Moreover, the C-reactive protein/albumin ratio (CAR) was also a significant predictor of PFS (P = 0.03). Furthermore, both factors were found to be independent factors influencing PFS in the univariate Cox regression analysis (P = 0.02 and P = 0.04).

Nal-IRI + 5FU/LV therapy may be a safe and effective option as a second- or later-line treatment, particularly for patients who have not previously received mFFX therapy. For patients who received prior mFFX exposure, a longer IFI and lower CAR may indicate greater potential benefit, thus aiding in more personalized treatment approaches.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis and high mortality. The prognosis for recurrence after surgery is extremely poor. Resection for disseminations of PDAC is not recommended.

The patient was a 69-year-old woman with a pancreatic tumor that was detected with computed tomography (CT) during a postoperative colon cancer checkup. She was suspected of having pancreatic body cancer without distant metastasis. Distal pancreatectomy with celiac axis resection was performed. Postoperative pathological examination revealed an invasive ductal adenocarcinoma with lymph node metastasis (pT4N1M0, stage III). Postoperatively, she received adjuvant chemotherapy containing gemcitabine and S-1 for 1 year and 4 months, and S-1 monotherapy for 1 year. Six years and 2 months after the initial surgery, her serum carbohydrate antigen 19-9 level elevated, and CT revealed soft tissue in front of the left kidney. Positron emission tomography/CT also revealed high fluorine-18 fluorodeoxyglucose uptake in the tissue. Accordingly, the patient was diagnosed with dissemination of PDAC. The patient was administered chemotherapy with gemcitabine and S-1. One year and 6 months after the diagnosis of dissemination, CT revealed reduction of the nodule. Therefore, we decided to eliminate this dissemination. A left nephrectomy and partial gastrectomy were performed. Histopathological examination confirmed dissemination of PDAC. The patient refused adjuvant chemotherapy. No evidence of recurrence has been observed for 13 years and 3 months since the initial surgery, and 5 years and 1 month since the resection of the dissemination.

This case showed a recurrence of dissemination after radical PDAC surgery, and the patient showed long-term survival without recurrence after dissemination resection. Resection of dissemination may confer long-term survival in selected patients.

Liver recurrence after resection is one of the most common types of recurrence and is a risk factor for poor prognosis. The aim of this study was to identify risk factors for initial liver recurrence.

A total of 109 patients with resectable pancreatic ductal adenocarcinoma who underwent resection between 2015 and 2022 were included. The influence of clinicopathologic variables on liver recurrence was analyzed to create a novel scoring system to predict liver recurrence.

The liver recurrence rate was 24%, with 17% recurrence within 1 year. Patients with liver recurrence had an extremely poor prognosis within 1 year (MST 12.4 [95% CI, 5.7-19.1]). In multivariate analysis, R-PV, large tumor diameter ≥45 mm, and venous invasion were independent risk factors for early liver recurrence. When each of these risk factors was scored as 1 point, the 1-year liver recurrence rates by score were 0 (0%), 1 (9%), 2 (30%), and 3 (84%).

The risk factors for postoperative early liver recurrence were R-PV, a tumor diameter ≥45 mm, and pathological venous invasion. Surgery for pancreatic cancer with these factors may require special treatment, such as hepatic arterial injection.

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.

We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection.

Background: This study aimed to assess the safety and efficacy of gemcitabine plus S-1-based chemoradiotherapy (GS-CRT) among patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), especially among those with unresectable locally advanced (UR-LA) cases. Methods: A total of 351 consecutive PDAC patients were enrolled and prognostic predictors of disease-specific survival (DSS) were identified. Results: The treatment completion rate was 98.9% and Grade 3 or higher adverse events occurred in 181 cases (51.6%). Among 319 re-evaluated patients, pancreatectomy was performed in 184 (57.7%). Based on resectability, the 5-year DSS rates for the entire cohort were 39.6% (R), 43.8% (BR-PV), 21.2% (BR-A) and 13.3% (UR-LA), while the predictors of DSS were performance status (PS), hemoglobin (Hb) level, celiac artery (CA) involvement of ≥180 degrees and JPS 8th T category. In the resected cases, the predictors of DSS were preoperative PS, preoperative CA19-9 level, preoperative JPS-T factor, degree of histological response and adjuvant chemotherapy. In UR-LA resected patients, preoperative prognostic nutritional index (PNI), absence of pathological venous invasion and adjuvant chemotherapy were predictors of DSS. Conclusions: Even though Grade 3 or higher adverse events were encountered in about half of the cases, they were uneventfully managed. Therefore, GS-CRT is safe and highly tolerable with potential to improve patients' prognosis. Preoperative PS, CA19-9 levels and histological response are important prognostic factors, as well as adjuvant therapy. In UR-LA patients, prognostic nutritional index (PNI) and adjuvant chemotherapy were important for curative intent surgery.

Patients diagnosed with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) have historically worse survival rates compared to those with resectable pancreatic cancer. The study aimed to assess the feasibility and efficacy of neoadjuvant chemotherapy and chemoradiotherapy in BRPC/LAPC. Additionally, we evaluated the R0 resection rates for patients who progressed to surgery.

This retrospective study included patients diagnosed with BRPC/LAPC between January 2019 and December 2023 at The Canberra Hospital (TCH), a tertiary care setting. A total of 115 patients were screened, of whom 37 were eligible for inclusion. Demographic data, CA19-9 levels, treatment regimens, surgical outcomes, resection rates, disease-free survival (DFS), and overall survival were analysed.

A total of 20 (54%) patients (15 FOLFIRINOX and 5 gemcitabine/nab-paclitaxel) completed their planned chemotherapy, and 17 (46%) of these patients had chemoradiotherapy, majority receiving 45-50 Gy of conventional radiation with capecitabine. Tumor marker Ca19-9 normalized after chemotherapy in seven patients (19%). In total, 23 patients (62.2%) progressed to surgery. The median DFS for all patients was 12.7 months (95% CI 5.5-15.9), and the median OS was 21 months (95% CI 13.7-44.9).

This study suggests that neoadjuvant treatment is feasible for BRPC/LAPC, allowing patients to undergo surgery and achieve R0 resection. However, further randomized controlled trials with larger cohorts are needed to validate these findings and refine treatment protocols.

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.

Randomized trials and meta-analyses have indicated longer survival with neoadjuvant than with adjuvant therapy in patients with resectable or borderline resectable (R/BR) pancreatic adenocarcinoma. Despite the efficacy of chemotherapy, the role of radiation therapy as an adjuvant or neoadjuvant treatment for patients with R/BR pancreatic adenocarcinoma remains unclear. In this systematic review and meta-analysis, we compared the benefits of additional chemoradiation therapy (CRT) to neoadjuvant chemotherapy (NAC) with NAC alone for R/BR pancreatic adenocarcinoma.

A systematic literature search was conducted on Embase, Web of Science, PubMed, Cochrane, and Google Scholar. Median overall survival (OS) was the primary endpoint. Secondary endpoints included disease-free survival (DFS), resection rate, and R0 resection rate.

This review and meta-analysis included 31 prospective studies, of which 9 were randomized trials. In these studies, 658 patients from 14 study arms received NAC alone and 912 patients from 19 study arms received both NAC and CRT (NAC-CRT). The pooled median OS was 25.55 months (95% CI, 21.59-30.24 months) for NAC alone and 17.55 months (95% CI, 16.47-18.70 months; P < .0001) for NAC-CRT. The pooled R0 resection rate was higher with NAC-CRT (83.43%) than with NAC (69.97%; P < .0001). No significant difference was observed in DFS or resection rate between the 2 groups. In patients who received 5 or more cycles of initial chemotherapy, NAC-CRT was associated with longer OS than NAC (23.30 vs 21.85 months; P = .856).

NAC provides significantly longer OS than NAC-CRT to R/BR pancreatic adenocarcinoma. NAC-CRT is associated with a significantly improved R0 resection rate. This positive local effect of CRT can be translated to extended survival when 5 cycles or more of NAC are prescribed.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited therapeutic options and poor overall survival. In recent years, advances in genomic profiling have revealed the complex molecular and cellular heterogeneity of PDAC, offering new avenues for therapeutic intervention.

This review explores emerging therapeutic strategies targeting dysregulated molecular pathways, along with the tumor microenvironment, that have shown promise in overcoming drug resistance. Novel immunotherapy strategies, such as immune checkpoint inhibitors and CAR T-cell therapies, are currently being explored in an attempt to modulate PDAC immugnosuppressive microenvironment. Additionally, we highlight recent clinical trials over the last 5 years and innovative therapeutic strategies aiming to improve outcomes in PDAC.

Significant progress in genomic profiling, targeted therapies, and immunotherapy is shaping the treatment of PDAC. Despite challenges posed by its dense stroma and immune suppressive microenvironment, novel strategies such as IL 6 and CD137 inhibitors, CAR-T, and therapeutic cancer vaccines are promising. KRAS targeted therapies are expanding beyond G12C inhibitors, with novel drugs in development that will further improve treatment options. Additionally, tumor treating fields (TTF) are being investigated in locally advanced PDAC, with the PANOVA-3 trial potentially integrating this modality into future treatment strategies. Continued advancements in these areas will significantly enhance PDAC outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, characterized by late diagnosis, rapid progression, and limited therapeutic options. Despite advancements, only 20% of patients are eligible for surgical resection at diagnosis, the sole curative treatment. Multidisciplinary evaluation is critical to optimize care, stratifying patients based on resectability into resectable, borderline resectable, locally advanced, and metastatic stages. Preoperative imaging, such as computed tomography (CT) and endoscopic ultrasound (EUS), remains central for staging, for vascular assessment, and tissue acquisition. Endoscopic and systemic approaches are pivotal for addressing complications like biliary obstruction and improving outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) has been considered for years the gold standard for biliary drainage, although EUS-guided drainage is increasingly utilized due to its efficacy in both resectable and unresectable disease. Systemic therapies play a key role in neoadjuvant, adjuvant, and palliative settings, with ongoing trials exploring their impact on survival and resectability chance. This review highlights the evolving multidisciplinary approaches tailored to the disease stage, focusing on biliary drainage techniques, systemic therapies, and their integration into comprehensive care pathways for PDAC. The continuous refinement of these strategies offers incremental survival benefits and underscores the importance of personalized, multidisciplinary management.

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

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

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

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

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

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

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

The aim of this study was to investigate how preoperative chemotherapy affected the serum zinc concentrations in patients with pancreatic cancer (PC).

Two hundreds thirty-one patients with PC who underwent pancreatectomy at our department from 2013 to 2019 were enrolled in this study and measured for the serum zinc concentrations before pancreatectomy. Patient characteristics, course of treatment, and laboratory data were analyzed.

One hundred thirty-five patients underwent upfront pancreatectomy and 58 received preoperative gemcitabine + S1 (GEM + S1) and 29 received gemcitabine + nab-paclitaxel (GEM + nab-PTX). Comparing the serum zinc concentrations before and after preoperative treatment, it was found to decrease after treatment with statistical difference (79.3 μg/dL vs 68.7 μg/dL, P < 0.001). The result was consistent with the investigation for both the patients who received GEM + S1 and those who received GEM + nab-PTX ( P = 0.019, P < 0.001, respectively).

The preoperative chemotherapy consistently reduced the serum zinc concentrations in the PC patients, regardless of their regimen such as GEM + S1 and GEM + nab-PTX. Monitoring the serum zinc concentration and appropriate zinc supplementation may be essential for PC patients undergoing preoperative chemotherapy and pancreatectomy.

Currently, neoadjuvant chemotherapy (NAC) is usually performed even for resectable pancreatic ductal adenocarcinoma (rPDAC). The present study investigated the benefits of NAC with gemcitabine plus S-1 for rPDAC. The medical records of 170 patients diagnosed as having rPDAC based on preoperative imaging were reviewed retrospectively. Clinicopathological factors in the NAC group were compared with those in the upfront surgery (UpS) group. NAC was administered to 30 of the 170 patients. The period from first visit to treatment in the NAC group was shorter than that in the UpS group (P<0.001). Staging laparoscopy detected occult distant metastases in 12 of the 170 patients (7%), of whom all 12 were in the UpS group. All patients in the NAC group underwent surgical resection (P=0.028). Among the 158 patients who underwent pancreatectomy, the NAC group showed rapid induction of the treatment, non-inferior operative outcomes and a higher R0 rate compared with the UpS group. Rates of early recurrence (within 6 months) after surgery were 10% (3/30) in the NAC group and 29% (37/128) in the UpS group (P=0.021). NAC for rPDAC is beneficial in terms of rapid induction of the treatment, fewer occult metastases, and lower rate of early recurrence.

The study aimed at assessing whether long-term survival outcomes were different based on tumor location in pancreatic ductal adenocarcinoma (PDAC) patients who underwent pancreatectomy following neoadjuvant chemoradiotherapy (CRT).

Following CRT, resection rate was 60.5% (286/473) and the resected patients had pancreatic head (n = 218), body (n = 34) and tail (n = 34) tumors. Survival analyses were conducted, independent predictors of disease-free survival (DFS) and overall survival (OS) were identified, and then survival outcomes were stratified by the predictors of DFS and OS.

Resection rates were; 64.7% (head) vs. 46.6% (body) and 54.0% (tail) cases, p = 0.009. Among these cases, pancreatic head patients exhibited a higher incidence of initial clinical stage 3 tumors; 48.2% (head) vs. 29.4% (body) and 0% (tail) cases, p < 0.001 with more unresctable-locally advanced tumors; 22.0% (head) vs. 11.8% (body) and 0% (tail), p < 0.001, but demonstrated a better response to CRT; Evans grades 3/4 in 49.1% (head) vs. 23.5% (body) and 26.5% (tail), p = 0.012. Five-year DFS rates were; 19.9% (head) vs. 11.8% (body) vs. 24.6% (tail), p = 0.565 and OS rates; 25.4% (head) vs. 27.7% (body) vs. 32.0% (tail), p = 0.341. Significant predictors of DFS and OS included post-CRT CA19-9 levels, tumor differentiation, resection margins and pathological portal vein invasion. Based on these predictors, survival outcomes were also comparable. Pathological nodal invasion influenced DFS, while pathological stage impacted OS.

Pancreatic head patients had the best resection rate and long-term survival outcomes were comparable, attributable to the better response to CRT by pancreatic head than the body and tail PDAC patients.

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.

This study aimed to investigate the effects of changes in clinicopathological factors during preoperative chemotherapy for pancreatic cancer, including skeletal muscle volume, on recurrence and prognosis after pancreatectomy.

Data from 41 patients who underwent resection for pancreatic cancer after preoperative chemotherapy from 2012 to 2021 were retrospectively reviewed. Skeletal muscle volume was substituted for the psoas muscle area (PMA) at the level of the third lumbar vertebra. We investigated the relationship of clinicopathological factors during preoperative chemotherapy with disease-free survival (DFS) and overall survival (OS). The association between clinicopathological factors and a decrease in PMA was investigated.

In the multivariate analyses for DFS and OS, the factors associated with recurrence were as follows: decrease in PMA (P = 0.003) and the absence of adjuvant therapy (P = 0.03), and the factors associated with poor prognosis were as follows: decrease in PMA (P = 0.04) and the absence of adjuvant therapy (P = 0.008), and the resectability of borderline resectable and unresectable-locally advanced tumors (P = 0.033). All patients with partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1) had no decrease in PMA (P = 0.01). The proportion of patients with Evans classification ≥ II was significantly higher in the group without a decrease in PMA (P = 0.02). The proportion of patients with an average relative dose intensity of adjuvant therapy ≥0.6 was significantly higher in the group without a decrease in PMA (P = 0.02).

Changes in preoperative skeletal muscle volume during preoperative chemotherapy for pancreatic cancer is a potential predictor of recurrence and prognosis after pancreatectomy.

This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT).

We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated.

Multivariate analyses identified osteosarcopenia (P = 0.049) and lymph node metastasis (P = 0.01) as independent recurrence predictors, and osteosarcopenia (P = 0.002), maximum tumor diameter ≥40 mm (P = 0.006), and no adjuvant therapy (P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher (P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007).

Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear.

Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas.

Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.

Creatine kinase (CK) levels decrease with cancer progression and muscle wasting, but its association with pancreatic ductal adenocarcinoma (PDAC) remains unclear. The aim of this study was to investigate CK as a prognostic biomarker and surrogate marker for muscle mass in patients with PDAC.

A retrospective analysis of 476 patients with PDAC was conducted. CK levels were categorized into low and high groups using receiver-operating characteristic (ROC) curve analysis.

Among the 476 patients, 200 (42.0%) and 276 (58.0%) were classified into the low and high CK groups, respectively. The low CK group had significantly poorer overall survival (p < .001) and recurrence-free survival (p < .001) compared to the high CK group. Multivariate analysis identified low CK as an independent poor prognostic factor (p < .001). The low CK group had significantly lower skeletal muscle index (p = .048) than the high CK group; however, the difference was slight and not significantly associated with sarcopenia. Additionally, combined risk assessment incorporating CK and resectability facilitated a more nuanced prognostic stratification.

CK served as a reliable prognostic marker independent from resectability but was less effective as a marker for sarcopenia in PDAC.

An increasing number of elderly patients are being diagnosed with pancreatic cancer, with increasing need to consider pancreatic surgery. This study aims to provide an updated systematic review and meta-analysis to evaluate the outcomes following pancreaticoduodenectomy in octogenarians.

A systematic review and meta-analysis was performed via a search of Medline, PubMed and Cochrane databases. Studies comparing outcomes of patients >80 years to younger patients undergoing PD were included.

26 studies were included. This included 22481 patients, with 20134 (89.6%) aged <80 years old, and 2347 (10.4%) octogenarians. Octogenarians were associated with higher rates of mortality (OR 2.37 (95%CI 1.91-2.94, p < 0.00001)), all-cause morbidity (OR 1.60 (95%CI 1.30-1.96), p<0.00001) and re-operation (OR 1.41 (95%CI 1.13-1.75), p = 0.002). Octogenarians had a two-fold risk of cardiac complications and respiratory complications (OR 2.13 (95%CI 1.67-2.73), p < 0.00001), (OR 2.38 (95%CI 1.72-3.27), p < 0.0001). There was no difference in postoperative pancreatic fistula, post-pancreatectomy hemorrhage or delayed gastric emptying. Younger patients were more likely to return to adjuvant therapy (OR 0.20 (95%CI 0.12-0.34), p < 0.00001).

Octogenerians are associated with higher mortality rate, postoperative complications, and reduced likelihood to undergo adjuvant therapy. Careful preoperative assessment and selection of elderly patients for consideration of pancreatic surgery is essential.

A recent study has demonstrated that the timing of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) significantly influences the peritoneal lavage cytology (CY) outcomes in pancreatic body-tail cancer. The aim of this study was to clarify the impact of EUS-FNA on CY positivity in patients with resectable pancreatic body-tail cancer.

Patients with anatomically resectable pancreatic body-tail cancer surgically resected at Hiroshima University Hospital were enrolled, and elated clinicopathological factors, including EUS-FNA variables and CY positivity rate, were analyzed.

Of the 129 eligible patients, 16 (12%) had positive CY. The EUS-FNA rates of the CY-positive and CY-negative groups were not significantly different (63% vs. 52%, p = .440). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for CY positivity (odds ratio: 5.734, p = .031). A total of 10 (14%) of the 69 patients who underwent EUS-FNA had positive CY; however, needle specifications and the interval between EUS-FNA and CY examination did not differ between the CY-positive and CY-negative groups. CY positivity rates were comparable for intervals ≤14 days and ≥15 days (17% vs. 14%, p = 1.000).

EUS-FNA may not affect CY positivity in patients with resectable pancreatic body-tail cancer, regardless of the timing.

This study evaluated the impact of renal function impairment on long-term survival outcomes and adjuvant therapy in patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD).

In this study, 264 patients who underwent PD for pancreatic head cancer between 2011 and 2021 were retrospectively analyzed. The patients were subsequently categorized into three groups according to the estimated glomerular filtration rate: normal group (> 90 mL/min/1.73 m2, n = 73), moderate group (45-90 mL/min/1.73 m2, n = 176), and severe group (< 45 mL/min/1.73 m2, n = 15). The primary outcomes evaluated were postoperative complications, overall survival (OS), and relapse-free survival (RFS). Additionally, the completion of adjuvant therapy and risk factors for adjuvant therapy discontinuation were analyzed.

The total proportion of patients with complications was significantly higher in the severe group (p = 0.008). The proportion of patients with severe complications (Clavien-Dindo classification ≥ IIIa) did not significantly differ between the chronic kidney disease (CKD) groups (p = 0.730). The proportion of patients in whom adjuvant therapy was completed was notably lower in the severe group (p = 0.011). Multiple logistic regression analysis revealed that CKD groups and hemoglobin levels ≤ 11.5 g/dL were independent predictors of adjuvant therapy completion failure (p = 0.016 and p = 0.016). There was no significant difference in the OS and RFS rates between the CKD groups (p = 0.499, p = 0.688).

In patients with pancreatic cancer and CKD, performing PD safely may be feasible; however, adjuvant therapy completion is challenging.

The prognostic impact of additional resection based on intraoperative frozen section analysis (FSA) of the pancreatic transection margin in patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. The purpose of this study was to evaluate the prognosis based on the results of the first FSA of the pancreatic transection margin (1st FSA) and the clinical significance of additional resection.

Patients who underwent pancreaticoduodenectomy for PDAC from 2000 to 2020 at a single center were included. Patients were divided into 3 groups based on the 1stFSA. Survival and prognostic factors were analyzed according to the 1stFSA.

A total of 311 patients were included in this study. The 1stFSA was negative in 272 patients (1stFSA-R0) and positive in 39 patients [carcinoma in situ (1stFSA-CIS), 21 patients; invasive carcinoma (1stFSA-IC), 18 patients]. Additional resections were performed on 37 patients [1stFSA-CIS, 20 patients; 1stFSA-IC, 17 patients], and R0 resection was achieved in 34 patients intraoperatively. Comparing median survival time to 1stFSA-R0 (36.4 months), 1stFSA-CIS was comparable (27.8 months, p = 0.276), although 1stFSA-IC was significantly worse (18.8 months, p = 0.001). On multivariate analysis, 1stFSA-IC was an independent prognostic factor (hazard ratio 2.68, 95 % confidence interval 1.16-6.17, p = 0.020).

1stFSA-CIS and 1stFSA-R0 had similar OS, implying that additional resection may be acceptable for 1stFSA-CIS. 1stFSA-IC was still an independent prognostic factor based on additional resection, and the prognostic significance of additional resection is uncertain for 1stFSA-IC.

The objective of this study is to analyze the outcomes of patients with resectable/borderline resectable PDAC who receive total neoadjuvant therapy vs upfront surgery.

Patients who were treated at a single institution from 2006 to 2021 were included. The primary outcome was overall survival (OS). Secondary outcomes included disease free survival (DFS), rates of lymph node positivity, and R0 resection. All survival analyses were performed with intention-to-treat.

26 patients received neoadjuvant chemotherapy and radiation (TNT), 28 received neoadjuvant chemotherapy only (NAC), and 168 received upfront surgery. Demographics were comparable across all three groups. Patients who received TNT or NAC had longer OS and DFS compared to the surgery first patients (P < .01). Patients who received TNT had a lymph node positivity rate of 0% at time of surgery compared to 5.3% and 13.3% in the NAC and surgery-first groups, respectively (P < .01). The rate of R0 resection did not differ between groups (P = .17).

Patients with resectable/borderline resectable PDAC who receive neoadjuvant therapy have longer OS and RFS relative to those who receive upfront surgery.

This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET).

The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed.

After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis.

R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.

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.