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

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

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

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

The introduction of (m)FOLFIRINOX and gemcitabine-nab-paclitaxel has changed the perspective for patients with locally advanced pancreatic cancer (LAPC). Consequently, in experienced centres 23% of patients with LAPC undergo a resection with 5-year overall survival (OS) rates of up to 25%. In the Netherlands, the nationwide resection rate for LAPC remains low at 8%. The PREOPANC-4 program aims for a nationwide implementation of the international multidisciplinary best-practice to improve patient outcome.

Nationwide program implementing the international multidisciplinary best-practice for LAPC. In the training phase, multidisciplinary and surgical webinars are given by 4 international experts, leading to a clinical protocol, followed by surgical off-site and on-site proctoring sessions. In the implementation phase, the clinical protocol will be implemented in all centres, including a nationwide expert panel (2022-2024). Healthcare professionals will be trained in shared decision-making. Consecutive patients diagnosed with pathology-proven LAPC (i.e., arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion [DPCG criteria]) are eligible. Primary outcomes are median and 5-year OS from diagnosis, resection rate, in-hospital/30-day mortality and major morbidity (i.e., Clavien-Dindo grade ≥ IIIa), and radical resection (R0) rate. Secondary outcomes include quality of life, functioning, side effects, and patients' healthcare satisfaction in all included patients. Outcomes will be compared with patients with borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX in the PREOPANC-2 trial (EudraCT: 2017-002036-17) and a historical cohort of patients with LAPC from the PACAP registry (NCT03513705). The existing prospective LAPC Registry and PACAP PROMs (NCT03513705) will be used for data collection. In qualitative interviews, treatment preferences, values, and experiences of LAPC patients, their relatives, and healthcare professionals will be assessed for the development of shared decision-making supportive tools. It is hypothesized that the program will double the nationwide LAPC resection rate to 16% with major morbidity < 50% and mortality ≤ 5%, and OS following resection similar to that observed in patients with BRPC.

The PREOPANC-4 program aims to safely implement the international multidisciplinary best-practice for LAPC leading to benchmark outcomes for both short-term morbidity, mortality, and OS.

PREOPANC-4 program was registered at ClinicalTrials.gov (NCT05524090) on September 1, 2022.

Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels, making its radical resection challenging. Multimodal treatment strategies, including neoadjuvant therapy, surgery, and postoperative adjuvant therapy, are contributing to a paradigm shift in the treatment of pancreatic cancer. This strategy is also promising in the treatment of pancreatic neck-body cancer.

To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer.

From January 2019 to December 2021, we reviewed the demographic characteristics, neoadjuvant and adjuvant treatment data, intraoperative and postoperative variables, and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital. This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria.

A total of 11 patients with pancreatic neck-body cancer were included in this study, of whom 6 patients were borderline resectable and 5 were locally advanced. Through multidisciplinary team discussion, all patients received neoadjuvant therapy, of whom 8 (73%) patients achieved a partial response and 3 patients maintained stable disease. After multidisciplinary team reassessment, all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection. Postoperatively, two patients (18%) developed ascites, and two patients (18%) developed pancreatic fistulae. The median length of stay of the patients was 11 days (range: 10-15 days). All patients received postoperative adjuvant therapy. During the follow-up, three patients experienced tumor recurrence, with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months.

A multimodal treatment strategy combining neoadjuvant therapy, laparoscopic subtotal distal pancreatectomy, and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.

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

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

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

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

The overall treatment response among patients with locally advanced pancreatic cancer (LAPC) is poorly understood as most studies report solely on resected patients. We aimed to investigate the outcomes in patients with LAPC as an intention-to-treat-analysis from the time of diagnosis from a complete source population.

An observational cohort study in a population-defined region within a universal healthcare system. All consecutive patients discussed at multi-disciplinary tumour board (MDT), aged ≥ 18 years and diagnosed with LAPC were included. Exposure was set as recommended treatment by MDT (i.e. upfront surgery, neoadjuvant therapy, palliative treatment or best supportive care). Outcome measures were overall survival analysed by Kaplan-Meier survival estimates and multivariable analyses using logistic regression for odds ratios (OR) and Cox proportional hazard analysis for hazard ratios (HR).

In total, 8803 MDT events (6055 unique patients) with pancreatic disease were held during the study period. Some 1436 (24%) had pancreatic cancer, of which 162 (11%) had LAPC and 134 met the population-defined criteria. In overall survival analyses, the patients who were recommended neoadjuvant therapy (± surgery) demonstrated no significant difference to palliative chemotherapy (median 11.0 months vs. 11.8 months; p = 0.226). In multivariable analysis, adjusted OR for overall survival comparing the treatment groups was 0.27 (95% CI 0.02-3.29, p = 0.306) and Cox proportional HR 0.96 (95% CI 0.58-1.59, p = 0.865).

In patients with LAPC, survival was not statistically different between those recommended for attempt at neoadjuvant (± surgery) compared with those recommended palliative chemotherapy. The findings suggest that conversion/downstaging chemotherapy is successful in only a select few.

It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.

Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes.

47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 ​%,p ​= ​0.001) and less likely to survive(16%vs56 ​%,p ​= ​0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32-10.25],HR survival:3.80[1.38-10.46]).

TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.

The purpose of this study was to provide a detailed evaluation of the oncological advantages of surgery following neoadjuvant chemotherapy (NAC) for patients with borderline resectable (BR) or unresectable (UR) pancreatic ductal adenocarcinoma (PDAC), with a focus on minimizing biases. Recently, NAC has become the standard care for BR or UR locally advanced (UR-LA) PDAC, however, many studies have assessed survival benefits and favorable variables without consideration for biases, particularly immortal time bias.

This study included patients diagnosed with BR or UR-LA PDAC at Juntendo University Hospital from 2019 to 2022. To mitigate bias, we applied methods such as propensity score matching (PSM), time-dependent covariate Cox proportional hazard regression analysis (TDC), landmark analysis, and multivariable Cox proportional hazards regression model.

The study analyzed 124 patients, dividing them into a surgery group (n = 57) and a chemotherapy-only group (n = 67). After PSM, there were 21 matched pairs. Survival analysis using TDC analysis showed that the surgery group had significantly better overall survival compared with the chemotherapy-only group in both the entire cohort and the matched pairs. Cox regression analysis of the entire cohort also revealed a similar superiority of surgery, while the landmark analysis showed varying results depending on the landmark setting.

After careful adjustment for selection and immortal time biases, surgery following NAC appears to significantly extend survival in patients with BR or UR PDAC.

Pancreatic duct adenocarcinoma (PDAC) accounts for about 85-90% of all solid pancreatic tumors, which is well-known for poor prognosis and high morbidity. Despite the massive advent of chemotherapy and radiotherapy in recent years, surgical removal is still considered the cornerstone management option in this situation. Pancreaticoduodenectomy or Whipple procedure is generally contraindicated in metastasis or tumors that encase more than 50% of vessels. Vascular reconstruction is a state-of-the-art technique which requires the remarkable involvement of vascular experts in the setting of PDAC-invading vessels. In this article, we present an exceptional case of a 38-year-old male patient who underwent radical resection for advanced pancreatic cancer with superior mesenteric vein reconstruction by a great saphenous vein.

The use of surgery in patients with locally advanced pancreatic cancer (LAPC) following induction chemotherapy is increasing. However, most series do not report on the total cohort of patients undergoing surgical exploration; therefore, this single-center study investigates outcomes among all consecutive patients with LAPC who underwent surgical exploration.

We conducted a retrospective, single-center analysis including all consecutive patients with LAPC (Dutch Pancreatic Cancer Group criteria) who underwent surgical exploration with curative intent (January 2014-June 2023) after induction therapy. Primary outcomes were resection rate and overall survival (OS) from the time of diagnosis.

Overall, 127 patients underwent surgical exploration for LAPC, whereby 100 patients (78.7%) underwent resection and 27 patients (21.3%) underwent a non-therapeutic laparotomy due to the extent of vascular involvement (n = 11, 8.7%) or occult metastases (n = 16, 12.6%). The overall in-hospital/30-day mortality rate was 0.8% and major morbidity was 31.3% (in patients after resection: 1.0% and 33.3%, respectively). The overall 90-day mortality rate was 5.5%, which included 3.1% mortality due to disease progression. Resection was associated with longer median OS {29 months (95% confidence interval [CI] 26-43) vs. 17 months (95% CI 11-26); p < 0.001} compared with patients undergoing non-therapeutic laparotomy, with corresponding 5-year OS rates of 28.4% and 7.7%. In Cox proportional hazard regression analysis, only pancreatic body/tail tumors independently predicted OS (hazard ratio 1.788 [95% CI 1.042-3.068]).

This single-center series found a resection rate of 78.7% in patients with LAPC selected for surgical exploration, with a low risk of mortality and morbidity in all explored patients and a 5-year OS rate after resection of 28.4%.

We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC).

BRPC patients were treated with IMRT (45 Gy/15fr) combined with two courses of S-1 (40 mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients.

Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29 vs. 20 months, p = 0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p < 0.001).

NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs-such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents-in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC.

The evolution and outcomes of extended pancreatectomies at a single institute over 15 years are presented in this study.

A retrospective analysis of the institutional database was performed from 2015 to 2022 (period B). Patients undergoing extended pancreatic resections, as defined by the International Study Group for Pancreatic Surgery, were included. Perioperative and survival outcomes were compared with data from 2007-2015 (period A). Regression analyses were used to identify factors affecting postoperative and long-term survival outcomes.

A total of 197 (16.1%) patients underwent an extended resection in period B compared to 63 (9.2%) in period A. Higher proportions of borderline resectable (5 (18.5%) versus 51 (47.7%), P = 0.011) and locally advanced tumours (1 (3.7%) versus 24 (22.4%), P < 0.001) were resected in period B with more frequent use of neoadjuvant therapy (6 (22.2%) versus 79 (73.8%), P < 0.001). Perioperative mortality (4 (6.0%) versus 12 (6.1%), P = 0.81) and morbidity (23 (36.5%) versus 83 (42.1%), P = 0.57) rates were comparable. The overall survival for patients with pancreatic adenocarcinoma was similar in both periods (17.5 (95% c.i. 6.77 to 28.22) versus 18.3 (95% c.i. 7.91 to 28.68) months, P = 0.958). Resectable, node-positive tumours had a longer disease-free survival (DFS) in period B (5.81 (95% c.i. 1.73 to 9.89) versus 14.03 (95% c.i. 5.7 to 22.35) months, P = 0.018).

Increasingly complex pancreatic resections were performed with consistent perioperative outcomes and improved DFS compared to the earlier period. A graduated approach to escalating surgical complexity, multimodality treatment, and judicious patient selection enables the resection of advanced pancreatic tumours.

Locally advanced cancers of the pancreatic body can abut or involve the celiac axis, hepatic artery, or superior mesenteric artery. Recent evidence suggests that these tumors are amenable to surgery after neoadjuvant chemotherapy (Hackert et al., Locally advanced pancreatic cancer: neoadjuvant therapy with FOLFIRINOX results in resectability in 60 % of the patients. Ann Surg 264:457-463, 2016; Rangelova et al., Surgery improves survival after neoadjuvant therapy for borderline and locally advanced pancreatic cancer: a single-institution experience. Ann Surg 273:579-86, 2021). An arterial divestment technique can be used for these cancers to get an R0 clearance, thereby avoiding morbid arterial resections (Miao et al., Arterial divestment instead of resection for locally advanced pancreatic cancer (LAPC). Pancreatology 16:S59, 2016; Habib et al., Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: surgical planning with the "halo sign" and "string sign." Surgery 169(5):1026-1031, 2021; Diener et al., Periarterial divestment in pancreatic cancer surgery. Surgery 169(5):1026-31, 2020). Two techniques are described for arterial divestment. In the periarterial divestment technique, the plane of the dissection is between the tumor and the adventitia (Habib et al., Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: surgical planning with the "halo sign" and "string sign." Surgery 169(5):1026-1031, 2021; Diener et al., Periarterial divestment in pancreatic cancer surgery. Surgery 169(5):1026-31, 2020). In sub-adventitial dissection, the plane of dissection is between the tunica adventitia and the external elastic lamina (Gao et al., Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study. Langenbecks Arch Surg 406:691-701, 2021). The TRIANGLE operation also is one of the surgical techniques to achieve R0 resection in locally advanced pancreatic cancer (Hackert et al., The TRIANGLE operation: radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single-arm observational study. HPB Oxford 19:1001-1007, 2017). This multimedia article aims to demonstrate peri-arterial and sub-adventitial divestment techniques as well as the TRIANGLE operation for a locally advanced cancer of the body of the pancreas. The video also highlights the technique of posterior radical antegrade modular pancreato-splenectomy (RAMPS) together with lymph node clearance.

A 57-year-old women was detected to have pancreatic body adenocarcinoma with tumor contact of the artery and superior mesenteric artery. After neoadjuvant chemotherapy, she was planned to undergo surgical resection.

The surgical technique consisted of peri-arterial and sub-adventitial divestment, the TRIANGLE operation and RAMPS (Fig. 1). The procedure was performed within 240 min and involved blood loss of 250 mL. After the procedure, pancreatic leak (POPF-B), chyle leak and diarrhea developed, which were managed conservatively. The final histopathology showed residual, viable, moderately differentiated adenocarcinoma (ypT2N1M0) with all resection margins free.

The surgical technique consisting of peri-arterial and sub-adventitial divestment, the TRIANGLE operation and RAMPS helps in R0 resection of locally advanced pancreatic body cancer without any compromise in oncologic outcomes and offers an alternative surgical approach to morbid arterial resection.

Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients.

Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed.

SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6).

Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.

Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX.

Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed.

With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy.

The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Cancer antigen 19-9 (CA19-9) is widely used as a marker of pancreatic cancer tumor burden and response to therapy. Synthesis of CA19-9 and its circulating levels are determined by variants encoding the fucosyltransferases, FUT2 and FUT3. Individuals can be grouped into one of four functional FUT groups (FUT3-null, FUT-low, FUT-intermediate, FUT-high), each with its own CA19-9 reference range based on its predicted capacity to produce CA19-9. The authors hypothesized that a FUT variant-based CA19-9 tumor marker gene test could improve the prognostic performance of CA19-9.

Preoperative and pre-treatment CA19-9 levels were measured, and FUT variants were determined in 449 patients who underwent surgery for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2010 and 2020, including 270 patients who underwent neoadjuvant therapy. Factors associated with recurrence-free and overall survival were determined in Cox proportional hazards models.

Higher preoperative CA19-9 levels were associated with recurrence and mortality for patients in the higher-FUT groups (FUT-intermediate, FUT-high for mortality, with adjustment for other prognostic factors; hazard ratio [HR], 1.34 and 1.58, respectively; P < 0.001), but not for those in the lower-FUT groups (FUT3-null, FUT-low). As a tumor marker, CA19-9 levels of 100 U/ml or lower after neoadjuvant therapy and normalization of CA19-9 based on FUT group were more sensitive but less specific predictors of evidence for a major pathologic response to therapy (little/no residual tumor) and of early recurrence (within 6 months).

Among patients undergoing pancreatic cancer resection, a CA19-9 tumor marker gene test modestly improved the prognostic performance of CA19-9.

In this perspective, we present our assessment of all of the known accumulated evidence on the role of neoadjuvant therapy in the management of borderline resectable pancreatic cancer highlighting the gaps in the data, the current regimens used and providing a brief insight into the way forward.

Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy.

A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion.

Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS.

Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy.

Despite the advancements in the treatment of localized pancreatic cancer, several unresolved issues persist in clinical practice, especially in the neoadjuvant setting. These include determining the criteria for selecting patients for treatment, identifying the most effective chemotherapy regimens, understanding the role of radiotherapy, and accurately assessing how patients respond to treatment. Current strategies for assessing patients before surgery involve thoroughly evaluating their overall health status, analyzing tumor markers, and using advanced imaging techniques. However, existing methods for staging the disease still have limitations when it comes to accurately detecting metastatic cancer. The ongoing debate between performing surgery upfront or administering neoadjuvant therapy highlights the need for robust clinical evidence to guide treatment decisions effectively. This review analyzes the evidence regarding controversial topics in neoadjuvant pancreatic cancer treatment and discusses further research efforts to enhance patient outcomes. To improve the outcomes found with surgery alone, multimodal treatment with chemotherapy.

To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX.

Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3).

With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS.

Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.

Systemic chemotherapy is the initial treatment strategy for borderline resectable and locally advanced pancreatic cancer to facilitate curative resection. The aim of this study was to investigate the resection rates and overall survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer.

Consecutive patients with borderline resectable pancreatic cancer/locally advanced pancreatic cancer discussed by Oslo University Hospital multidisciplinary team between 2018 and 2020, serving a population of 3.1 million within a geographically defined area in south-eastern Norway, were included in this prospective Norwegian Pancreatic Cancer Trial-2 study, according to intention-to-treat principles. The total number of patients with pancreatic cancer was sought from the Cancer Registry of Norway.

A total of 1178 patients were diagnosed with pancreatic cancer, of whom 618 were referred to Oslo University Hospital. After multidisciplinary team evaluation, 230 patients were considered to have borderline resectable pancreatic cancer/locally advanced pancreatic cancer. The final study group consisted of 188 patients (borderline resectable pancreatic cancer n = 96, locally advanced pancreatic cancer n = 92) who were fit to receive primary chemotherapy. Resection rates were 46.9% (45 of 96) for borderline resectable pancreatic cancer and 13% (12 of 92) for locally advanced pancreatic cancer (P <0.001). Median overall survival was 14.6 months (borderline resectable pancreatic cancer 16.4 months; locally advanced pancreatic cancer 13.7 months, (P = 0.2)). Adjusted for immortal time bias, median overall survival for patients undergoing resection versus only chemotherapy was 24.4 months versus 10.1 months (P <0.001) for borderline resectable pancreatic cancer and 28.4 months versus 12.6 months for locally advanced pancreatic cancer (P = 0.001).

Resection rates and survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer treated at a high-volume centre in a universal healthcare system compare well with those treated at international expert centres.Registration number: NCT04423731 (http://www.clinicaltrials.gov).

Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M).

In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles.

From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted.

Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO.

gov, Number: NCT03870386.

Arterial resection (AR) during pancreatectomy for curative R0 resection of pancreatic ductal adenocarcinoma (PDAC) remains a controversial procedure with high morbidity.

To investigate the feasibility and oncological outcomes of pancreatectomy combined with AR at a high-volume center for pancreatic surgery.

We retrospectively analyzed our experience in PDAC patients, who underwent pancreatic resection with AR and/or venous resection (VR) between 2007 and 2021.

In total 259 PDAC patients with borderline resectable (n = 138) or locally advanced (n = 121) PDAC underwent vascular resection during tumor resection. From these, 23 patients had AR (n = 4 due to intraoperative injury, n = 19 due to suspected arterial infiltration). However, 12 out of 23 patients (52.2%) underwent simultaneous VR including 1 case with intraoperative arterial injury. In comparison, 11 patients (47.8%) underwent AR only including 3 intraoperative arterial injury patients. Although the operation time and bleeding rate of patients with AR were respectively longer and higher than in VR, no significant difference was detected in postoperative complications between VR and AR (P = 0.11). The final histopathological findings of PDAC patients were similar, including M stage, regional lymph node metastases, and R0 margin resection. The mortality of the entire cohort was 6.2% (16/259), with a tendency to increase mortality in the AR cohort, yet without statistical significance (VR: 5% vs AR: 21.1%; P = 0.05). Although 19 (82.6%) patients had PDAC in the final histopathology, only 6 were confirmed to have infiltrated arteria. The microscopic distribution of PDAC in these infiltrated arterial walls on hematoxylin-eosin staining was classified into 3 patterns. Strikingly, the perivascular nerves frequently exhibited perineural invasion.

AR can be performed in high-volume centers for pancreatic surgery with an acceptable morbidity, which is comparable to that of VR. However, the likelihood of arterial infiltration seems to be rather overestimated, and as such, AR might be avoidable or replaced by less invasive techniques such as divestment during PDAC surgery.

Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.

Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.

We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.

A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.

In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

We analyze successes and failures of pushing the boundaries in vascular pancreatic surgery to establish safety of conduit reconstructions.

Improved systemic control from chemotherapy in pancreatic cancer is increasing the demand for surgical solutions of extensive local vessel involvement, but conduit-specific data are scarce.

We identified 63 implanted conduits (41% autologous vessels, 37% allografts, 18% PTFE) in 56 pancreatic resections of highly selected cancer patients between October 2013 and July 2020 from our prospectively maintained database. Assessed parameters were survival, perioperative complications, operative techniques (anatomic and extra-anatomic routes), and conduit patency.

For vascular reconstruction, 25 arterial and 38 venous conduits were utilized during 39 pancreatoduodenectomies, 14 distal pancreatectomies, and 3 total pancreatectomies. The median postoperative survival was 2 years. A Clavien-Dindo grade ≥IIIa complication was apparent in 50% of the patients with a median Comprehensive Complication Index of 29.6. The 90-day mortality in this highly selected cohort was 9%. Causes of mortality were conduit related in 3 patients, late postpancreatectomy hemorrhage in 1 patient, and early liver metastasis in 1 patient. Image-based patency rates of conduits were 66% and 45% at postoperative days 30 and 90, respectively.

Our perioperative mortality of vascular pancreatic surgery with conduits in the arterial or venous system is 9%. Reconstructions are technically feasible with different anatomic and extra-anatomic strategies, while identifying predictors of early conduit occlusion remains challenging. Optimizing reconstructed arterial and venous hemodynamics in the context of pancreatic malignancy will enable long-term survival in more patients responsive to chemotherapies.