Although the American Joint Committee on Cancer (AJCC) 8th edition recommends harvesting at least 12 lymph nodes for optimal staging in pancreatic ductal adenocarcinoma (PDAC), the precise lymph node yield (LNY) needed for accurate prognostication in different treatment settings remains unclear. This study aimed to identify subgroup-specific LNY cutoffs and evaluate their prognostic significance in nonmetastatic PDAC.

We analyzed 5609 patients with nonmetastatic PDAC from the Surveillance, Epidemiology, and End Results (SEER) database undergoing pancreatectomy. Patients were categorized by nodal status (N0 vs. N+) and receipt of neoadjuvant therapy (NAT) or upfront surgery (UPS). We used maximum selected rank statistics and a conditional inference tree approach to determine optimal LNY cutoffs for each subgroup. Kaplan-Meier curves and Cox proportional hazards models were employed to assess cancer-specific survival (CSS) and identify independent prognostic factors.

Distinct LNY thresholds were identified for N0 (>13) and N+ (>10) cohorts, with the highest cutoffs in N0-NAT subgroups (>27). Across all analyses, patients exceeding these LNY cutoffs demonstrated significantly prolonged CSS. The N0-NAT group with LNY >27 achieved the longest median survival (60 months), whereas N+ patients undergoing UPS with LNY ≤10 had the poorest outcomes (16 months). Multivariate Cox regressions consistently showed that higher LNY was an independent predictor of improved survival.

Higher LNY thresholds than the current AJCC standard of 12 appear beneficial for more accurate staging and improved survival in resected PDAC. Tailoring LNY goals based on nodal status and treatment modality may further refine prognostic stratification and guide more effective therapeutic strategies.

We investigated the rational extent of regional lymphadenectomy and evaluated the prognostic impact of number-based regional nodal classification in patients with distal cholangiocarcinoma.

This study included 191 patients with distal cholangiocarcinoma who underwent pancreaticoduodenectomy. The nos. 8, 12a-b-c-p, 13, 14, and 17 nodes were dissected routinely. The impact of the extent of lymphadenectomy on prognostic stratification performed using number-based nodal classification was evaluated.

The incidence of metastasis in the routinely dissected nodes was 1.0-25.7%, with 5-year overall survival of 0-36.4% in patients with metastasis. The incidence of metastasis in the no. 12p nodes, which were not included in regional nodes in the American Joint Committee on Cancer or International Union Against Cancer staging systems, was 5.8% with a 5-year overall survival of 36.4% in patients with metastasis. When our dissected nodes were adopted (P < .001), number-based nodal classification predicted overall survival better than when regional nodes defined by the International Union Against Cancer or American Joint Committee on Cancer staging systems were used (nos. 8, 12a-b, 13, 14, and 17 nodes with or without no. 9 nodes; P = .004 each). The 5-year overall survival in patients with pN0, pN1 (1-3 positive nodes), and pN2 (≥4 positive nodes) disease was 57.4%, 37.3%, and 13.6%, respectively (P < .001). The pN classification was an independent prognostic factor (pN1, P = .009; pN2, P < .001).

The nos. 8, 12a-b-c-p, 13, 14, and 17 nodes should be prioritized as the rational extent of regional lymphadenectomy for distal cholangiocarcinoma for accurate staging. Number-based regional nodal classification is suitable for prognostic stratification.

The optimal resection for pancreatic neck cancer is challenging in clinical practice because we could dissect by pancreaticoduodenectomy or distal pancreatectomy. The purpose of this study was to evaluate the effectiveness of lymph node dissection and to help determine the optimal surgical treatment for pancreatic neck cancer.

We retrospectively evaluated 462 patients with pancreatic cancer who underwent curative-intent pancreatectomy between 2012 and 2022, 35 of whom had pancreatic neck cancer without preoperative radiologic gastroduodenal artery contact. We analyzed the clinicopathological characteristics, lymph node metastasis stations, and the efficacy index of lymph node dissection, which was calculated by multiplying the frequency of lymph node metastasis to each station by the 5-year survival rate of patients with positive lymph nodes at each station.

The lymph node station with the greatest rate of metastasis was #11p (28.6%), followed by #8 (17.1%), #14 (14.3%), #13 (14.3%), #17 (9.5%), and #6 (4.8%). The efficacy indices of lymph node dissection were 14.3 for #11, 4.76 for #13, and 8.57 for #14. There were no significant differences in 5-year recurrence-free survival and 5-year overall survival between patients undergoing pancreaticoduodenectomy and those undergoing distal pancreatectomy (23.7% vs 54.7%, P = .142; 29.9% vs 51.1%, P = .179, respectively). Univariate survival analysis showed that tumor size ≥2 cm was associated with poor prognosis (hazard ratio, 3.842, P = .009).

PD with #11p lymph node dissection is preferable to DP in terms of survival benefit for pancreatic neck cancer with lymph node metastasis.

The influencing role of resection margin (R) status on long-term outcomes, namely overall (OS) and disease-free survival (DFS), after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is not still clear. The aim of this study is to evaluate the prognostic impact of R status after PD and to define tumor characteristics associated with a positive resection margin (R1). All PDs for PDAC performed between 2012 and 2023 were retrospectively enrolled. The effect of R status, patient clinico-demographic features, and tumor features on OS and DFS were assessed. One-hundred and sixty-seven patients who underwent PD for PDAC were included in the study. R0 was achieved in 105 cases (62.8%), while R1 was evidenced in 62 patients (37.1%). R1 was associated with a decreased OS (23 (13-38) months) as compared to R0 (36 (21-53) months) (p = 0.003). Similarly, DFS was shorter in R1 patients (10 (6-25) months) as compared to the R0 cohort (18 (9-70) months) (p = 0.004), with a consequent higher recurrence rate in cases of R1 (74.2% vs. 64.8% in the R0 group; p = 0.04). In the multivariate analysis, R1 and positive lymph nodes (N+) were the only independent influencing factors for OS (OR: 1.6; 95% CI: 1-2.5; p = 0.03 and OR: 1.7; 95% CI: 1-2.8; p = 0.04) and DFS (OR: 1.5; 95% CI: 1-2.1; p = 0.04 and OR: 1.8; 95% CI: 1.1-2.7; p = 0.009). Among 111 patients with N+ disease, R1 was associated with a significantly decreased DFS (10 (8-11) months) as compared to R0N+ patients (16 (11-21) months) (p = 0.05). In conclusion, the achievement of a negative resection margin is associated with survival benefits, particularly in cases of N1 disease. In addition, R0 was recognized as an independent prognostic feature for both OS and DFS. This further outlines the relevant role of radical surgery on long-term outcomes.

There is no consensus on the utility of para-aortic lymph node dissection (PALND) in patients undergoing pancreaticoduodenectomy (PD) for periampullary cancer. The objective of this study was to assess survival in patients who underwent PD with PALND for pancreatic (PAC) and non-pancreatic (non-PAC) adenocarcinoma. All patients who underwent PD and PALND between 2011 and 2019 were reviewed (n = 114). We looked at the impact of tumor type (PAC versus non-PAC) and pathologically confirmed PALN metastasis (PALNM) on overall survival (OS). Out of 114 patients, PALNM were pathologically confirmed in 17(14.9%) patients. Without PALND, pathological staging would be pN0 in1(0.8%), pN1 in 3(2.5%), and pN2 in 13(11.2%) patients. The 30-day mortality was 3(2.6%) and 65(57%) patients received adjuvant treatment. The 4-year OS for PAC and non-PAC was 9% and 39% (P = 0.001). Advanced nodal involvement (pN2) was seen in 14/17(82.4%) and 21/97(21.6%) patients with and without PALNM, respectively (P < 0.001). For PAC, 4-year OS for patients with pN0-N1, pN2, and PALNM was 12%, 8%, and not reached (P = 0.067). For non-PAC, 4-year OS was 45%, 19%, and 12% (P = 0.006). In patients with non-PAC, despite metastatic involvement of PALN, acceptable long-term survival can be achieved with curative resection. For PAC, survival benefit with curative resection remains questionable.

To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT).

The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial.

Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1 mm and R 1 ≤1 mm resections.

Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005).

The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1 mm should be a primary goal in the surgical treatment of PDAC after NAT.

The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC.

Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging.

Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification.

The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.

Patients with pancreatic cancer (PC) have a poor prognosis. Radiotherapy (RT) is a standard palliative treatment in clinical practice, and there is no effective clinical prediction model to predict the prognosis of PC patients receiving radiotherapy. This study aimed to analyze PC's clinical characteristics, find the factors affecting PC patients' prognosis, and construct a visual Nomogram to predict overall survival (OS).

SEER*Stat software was used to collect clinical data from the Surveillance, Epidemiology, and End Results (SEER) database of 3570 patients treated with RT. At the same time, the relevant clinical data of 115 patients were collected from the Affiliated Cancer Hospital of Zhengzhou University. The SEER database data were randomly divided into the training and internal validation cohorts in a 7:3 ratio, with all patients at The Affiliated Cancer Hospital of Zhengzhou University as the external validation cohort. The lasso regression was used to screen the relevant variables. All non-zero variables were included in the multivariate analysis. Multivariate Cox proportional risk regression analysis was used to determine the independent prognostic factors. The Kaplan-Meier(K-M) method was used to plot the survival curves for different treatments (surgery, RT, chemotherapy, and combination therapy) and calculate the median OS. The Nomogram was constructed to predict the survival rates at 1, 3, and 5 years, and the time-dependent receiver operating characteristic curves (ROC) were plotted with the calculated curves. Calculate the area under the curve (AUC), the Bootstrap method was used to plot the calibration curve, and the clinical efficacy of the prediction model was evaluated using decision curve analysis (DCA).

The median OS was 25.0, 18.0, 11.0, and 4.0 months in the surgery combined with chemoradiotherapy (SCRT), surgery combined with radiotherapy, chemoradiotherapy (CRT), and RT alone cohorts, respectively. Multivariate Cox regression analysis showed that age, N stage, M stage, chemotherapy, surgery, lymph node surgery, and Grade were independent prognostic factors for patients. Nomogram models were constructed to predict patients' OS. 1-, 3-, and 5-year Time-dependent ROC curves were plotted, and AUC values were calculated. The results suggested that the AUCs were 0.77, 0.79, and 0.79 for the training cohort, 0.79, 0.82, and 0.81 for the internal validation cohort, and 0.73, 0.93, and 0.88 for the external validation cohort. The calibration curves Show that the model prediction probability is in high agreement with the actual observation probability, and the DCA curve shows a high net return.

SCRT significantly improves the OS of PC patients. We developed and validated a Nomogram to predict the OS of PC patients receiving RT.

The prognostic impact of radiographic duodenal invasion (rDI) of pancreatic ductal adenocarcinoma (PDAC) has yet to be fully elucidated. This retrospective study aimed to investigate the prognostic and clinicopathological significance of rDI in patients with PDAC after pancreatoduodenectomy (PD).

We retrospectively analyzed 223 consecutive patients with resectable (R) and borderline resectable (BR)-PDAC that underwent up-front PD between 2002 and 2018. rDI was assessed by preoperative multi-detector row computed tomography.

Ninety-three (42%) patients with PDAC had rDI, and all of them had pathological DI (pDI). The rDI(+) group had larger tumor size, BR-PDAC was more common, there was higher serum CA19-9 level, and microscopic lymphovascular invasion was more common than in the rDI(-) group. rDI was associated with significant reduction in overall survival (OS) (P < 0.001) and recurrence-free survival (RFS) (P < 0.001). In multivariate analysis, rDI was an independent prognostic factor in OS [hazard ratio (HR) = 0.52; 95% confidence interval (CI) 0.38-0.73, P < 0.001] and RFS [HR = 0.56; 95% CI 0.40-0.78, P = 0.001]. rDI was also an independent risk factor for early recurrence within 12 months [odds ratio (OR) = 0.36; 95% CI 0.18-0.73, P = 0.005]. rDI had positive correlation with liver recurrence (P = 0.024).

Biological aggressiveness of PDAC with rDI implies short OS and early recurrence with frequent liver metastasis. Aggressive perioperative chemotherapy is recommended to improve prognosis, especially for R-PDAC patients with rDI.

Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC).

We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score.

A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration.

Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

To investigate the outcome of conversion surgery in patients with metastatic pancreatic cancer (mPDAC) and to identify patients who may benefit from this approach.

The role of conversion surgery in patients with mPDAC and exceptional response to chemotherapy remains unclear.

Patients who underwent surgical exploration for mPDAC following chemotherapy between 2006 and 2019 were included. Data on demographics, oncologic treatment, pathology, and postoperative outcomes were analyzed. Univariate and multivariate survival analyses were performed.

Some 173 patients received preoperative chemotherapy and underwent surgical exploration. Ninety-three patients underwent resection of the primary tumor and metastatic sites, 80 patients underwent exploration only. In the resection subgroup, 45 patients had complete pathological response of metastases (ypM0) and 48 patients had residual metastases (ypM1). ypM0 status was associated with lower carcinoembryonic antigen levels and lower ypN stage. Overall survival after resection was 25.5 months in ypM0, 10.7 months in ypM1, and 8.1 months in patients without resection ( P <0.001). Additional adjuvant chemotherapy was significantly associated with prolonged survival in resected patients (29.0 vs 14.8 mo, P =0.024) as well as in ypM0 (29.1 vs 19.2 mo, P =0.047). Multivariable analysis identified conversion surgery, carbohydrate antigen 19-9 (CA19-9) and time of resection as independent prognostic markers for the entire cohort. CA19-9, ypM0 and adjuvant treatment were independent predictors of survival in the resection subgroup.

In patients with mPDAC and ypM0 status after chemotherapy, surgical resection is associated with encouraging survival. mPDAC patients with exceptional response to chemotherapy may be candidates for exploration and for resection in ypM0. Adjuvant chemotherapy may provide an additional survival advantage.

Lymph node and resection margin status are associated with oncologic outcomes after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. However, surgical radicality at the portomesenteric axis in case of suspected infiltration remains controversial.

Clinicopathological data of patients who underwent a partial or total pancreaticoduodenectomy for PDAC between 2012 to 2019 in 2 major hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We evaluated the impact of positive resection margins at the vascular, parenchymal, and retropancreatic surfaces on overall survival in patients with and without lymph node involvement. Margin-positive vascular resection included both patients with positive margins at the vascular groove and the resected venous wall.

During the study period, 217 patients underwent partial/total pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. After excluding 7 patients suffering postoperative complications resulting in mortality within 90 days after surgery (3%), 169 patients had lymph node involvement (80%). In the entire study cohort, margin-positive resection (33%) was significantly associated with worse overall survival (3-year overall survival: margin-positive resection: 27% vs margin-negative resection: 43%, P = .014). Among patients with positive lymph nodes, margin-positive vascular resection (n = 48, 28%) was not significantly associated with impaired overall survival (3-year overall survival: margin-positive vascular resection: 28% vs margin-negative vascular resection: 36%, P = .065). On the contrary, margin-positive parenchymal resection (n = 7, 4%) (3-year overall survival: margin-positive parenchymal resection: 0% vs margin-negative parenchymal resection: 35%, P < .0001) and margin-positive retropancreatic resection (n = 21, 12%) (3-year overall survival: margin-positive retropancreatic resection: 6% vs margin-negative retropancreatic resection: 39%, P < .0001) significantly diminished overall survival in univariate and multivariate analysis in all patients. Among patients without lymph node involvement (n = 41, 20%), there were no margin-positive parenchymal or margin-positive retropancreatic resections. In contrast, only 5 patients had margin-positive vascular resection (12%), with overall survival compared to those with margin-negative vascular resection.

In patients with pancreatic ductal adenocarcinoma and lymph nodal positivity, resection status at the parenchymal and retropancreatic surface but probably not at the portal and/or superior mesenteric vein is a determinant of survival. Therefore, margin-negative resection should be pursued during pancreaticoduodenectomy. However, radical venous resection and/or reconstruction for suspected tumor infiltration may not be necessary for patients with intraoperatively detected lymph node metastases.

Lymph nodes (LNs)' metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations' metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81-4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8-9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14-15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.

Pancreatic ductal adenocarcinoma (PDAC) contacting major arteries such as the celiac, common hepatic, and superior mesenteric artery is linked to poor prognosis and classified as borderline resectable. Although PDAC involving the gastroduodenal artery (GDA) is considered resectable, the prognostic impact of GDA involvement remains unclear. Here we investigated the prognostic impact of GDA involvement in PDAC after resection.

This study included 105 patients with resectable PDAC or borderline resectable with portal vein involvement. Patients were divided into two groups: those with tumor-GDA contact ≤ 180° and those with GDA contact > 180°. We evaluated the prognostic impact of GDA involvement between these groups.

Both recurrence-free and overall survival after the surgery were significantly poorer with GDA contact > 180° than ≤ 180°. The poorer prognosis with GDA contact > 180° was verified by multivariate analysis and propensity score matching analysis to match patient backgrounds between the groups. The frequency of postoperative distant metastasis was also significantly higher in patients with GDA contact > 180°.

GDA involvement is an independent factor significantly associated with postoperative survival in PDAC, and the poorer prognosis with GDA involvement may be linked to the development of postoperative distant metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a major public health issue with an incidence/mortality ratio reaching 98 %. Only 15-20 % of patients with PDAC can undergo surgery. Following PDAC surgical resection, 80 % of patients will experience local or metastatic recurrence of this disease. pTNM staging is the gold standard for risk stratification but is not sufficient to recapitulate the prognosis. Several prognostic factors are known to impact survival after surgery when uncovered during pathological examination. However, necrosis has been poorly studied in pancreatic adenocarcinoma.

We retrieved clinical data and reviewed all tumor slides from patients who had a pancreatic surgery between January 2004 and December 2017, in the Hospices Civils de Lyon, to assess the presence of histopathological prognosis factors associated with poor prognosis.

514 patients with complete clinico-pathological description were included. Necrosis was found in 231 PDAC (44.9 %) and had an important impact on overall survival with a double risk of death when present in tumor samples (HR: 1.871, 95 % CI [1.523; 2.299], p < 0.001). When integrated in the multivariate model, necrosis is the only morphological aggressive feature to retain high statistical significance associated with the TNM staging but independently of it. This effect is independent of the preoperative treatment.

Despites improvement in treatment of PDAC, mortality rates remain relatively stable amongst the last years. There is a desperate need to better stratify patients. Here, we report the strong and prognostic impact of necrosis in surgical PDAC samples and encourage pathologists to report its presence in the future.

The role of extended lymphadenectomy as part of resection for lymph node (LN)-positive gastrointestinal (GI) malignancies remains controversial with no clear clinical guidance. The purpose of this retrospective study is to determine whether the number of LNs examined as part of GI malignancy resections affects overall survival (OS) among patients with node-positive esophageal, gastric, pancreatic, and colon cancers.

Participants with LN-positive GI cancers who were diagnosed between 2004 and 2015 and underwent oncologic resections were selected from National Cancer Database (NCDB). The primary predictor was the number of examined LNs categorized in tertiles. The effect on OS was measured by hazard ratio (HR) derived from multivariate Cox regression analyses.

From 2004 to 2015, 1877, 10,086, 18,193, and 102,500 patients with LN-positive esophageal, gastric, pancreatic, and colon adenocarcinomas who did not receive neoadjuvant treatment and underwent oncologic tumor resection were registered in the NCDB. Using multivariate Cox proportional hazard modeling, greater LNs examined in surgically resected LN-positive GI cancers were found to be associated with increased OS for all histologies. This association was the strongest (as compared to the lowest tertile) for gastric cancer (middle tertile: HR = 0.91, 95% CI, 0.86-0.96, p = 0.001; highest tertile: HR = 0.73, 95% CI, 0.69-0.78, p < 0.001), followed by colon (highest tertile: HR = 0.86, 95% CI, 0.84-0.88, p < 0.001), esophageal (highest tertile: HR = 0.83, 95% CI, 0.72-0.95, p = 0.01), and pancreatic (highest tertile: HR = 0.93, 95% CI, 0.89-0.98, p = 0.002) cancers.

In patients with surgically resected node-positive GI malignancies who did not receive neoadjuvant systemic therapy, a higher number of examined LNs is associated with increased OS. This association is the strongest for gastric cancer, followed by colon, esophageal, and pancreatic cancers respectively.

Extranodal extension (ENE) is an established prognostic factor in several gastrointestinal cancers. However, the prognostic impact remains unclear. Here, we investigated the prognostic implications of ENE in patients with surgically resected pancreatic cancer.

We retrospectively reviewed 476 surgically resected pancreatic head cancer patients who consecutively underwent upfront pancreaticoduodenectomy for pathologically confirmed pancreatic ductal adenocarcinoma between January 2009 and December 2013. We compared the disease-free survival (DFS) rates of the patients according to ENE status.

Among the 476 patients, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; LN+/ENE-, 7 months; LN+/ENE+, 6 months; P < .001). In addition, even in the same N stage, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; N1/ENE- 8 months; N1/ENE+, 7 months; N2/ENE-, 7 months; N2/ENE+, 4 months, P < .001). However, there was no significant difference in survival rates between patients in the N1/ENE+ group and those in the N2/ENE- group. Additionally, ENE was an independent prognostic factor for pancreatic cancer.

Extranodal extension significantly predicted a poor prognosis among patients with pancreatic head cancer, especially those with nodal metastasis. Therefore, ENE should be considered a prognostic factor in future editions of the staging system.

Cancer of the pancreas is a life-threatening condition and has a high distant metastasis (DM) rate of over 50% at diagnosis. Therefore, this study aimed to determine whether patterns of distant metastases correlated with prognosis in pancreatic ductal adenocarcinoma (PDAC) with metastatic spread, and build a novel nomogram capable of predicting the 6, 12, 18-month survival rate with high accuracy.

We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for cases of PDAC with DM. Kaplan-Meier analysis, log-rank tests and Cox-regression proportional hazards model were used to assess the impact of site and number of DM on the cancer-specific survival (CSS) and over survival (OS). A total of 2709 patients with DM were randomly assigned to the training group and validation group in a 7:3 ratio. A nomogram was constructed by the dependent risk factors which were determined by multivariate Cox-regression analysis. An assessment of the discrimination and ability of the prediction model was made by measuring AUC, C-index, calibration curve and decision curve analysis (DCA). In addition, we collected 98 patients with distant metastases at the time of initial diagnosis from Ningbo University Affiliated LiHuili Hospital to verify the efficacy of the prediction model.

There was a highest incidence of liver metastases from pancreatic cancer (2387,74.36%), followed by lung (625,19.47%), bone (190,5.92%), and brain (8,0.25%). The prognosis of liver metastases differed from that of lung metastases, and the presence of multiple organ metastases was associated with poorer prognosis. According to univariate and multivariate Cox-regression analyses, seven factors (i.e., diagnosis age, tumor location, grade of tumor differentiation, T-stage, receipt of surgery, receipt of chemotherapy status, presence of multiple organ metastases) were included in our nomogram model. In internal and external validation, the ROC curves, C-index, calibration curves and DCA were calculated, which confirmed that this nomogram can precisely predict prognosis of PDAC with DM.

Metastatic PDAC patients with liver metastases tended to have a worse prognosis than those with lung metastases. The number of DM had significant effect on the overall survival rate of metastatic PDAC. This study had a high prediction accuracy, which was helpful clinicians to analyze the prognosis of PDAC with DM and implement individualized diagnosis and treatment.

In patients with pancreatic ductal adenocarcinoma (PDAC) in the pancreatic body (Pb) and tail (Pt), the appropriate area for lymphadenectomy is controversial. This study aimed to reevaluate the extent of lymph node (LN) metastasis in Pb- and Pt-PDAC, and to define the optimal area of LN dissection.

This single-center retrospective study evaluated patients with Pb- and Pt-PDAC who underwent distal pancreatectomy with extended lymphadenectomy between 2006 and 2020. LN metastasis in >3.0% of patients were defined as new regional LN.

The study cohort included 135 patients with Pb-PDAC and 42 patients with Pt-PDAC. In patients with Pb-PDAC, LNs around the splenic artery (SPA) had the highest metastasis-positive rate (54.1%). LNs along the left gastric artery, common hepatic artery, celiac axis (CA), superior mesenteric artery (SMA), and splenic hilus were defined as new regional LNs. In patients with Pt-PDAC, LNs at the splenic hilum had the highest metastasis-positive rate (38.1%). The station and LN around the SPA were defined as new regional LNs in those with Pt-PDAC. Metastasis beyond the newly defined regional LNs was not associated with survival. The incidence of LN metastasis was lower in patients who received preoperative chemotherapy than in those who underwent upfront surgery in both Pb- and Pt-PDAC.

Although it needs to be verified in future multicenter studies, LN of both the CA and SMA systems should be dissected in patients with Pb-PDAC. However, only those around the SPA and splenic hilus should be dissected routinely in those with Pt-PDAC.

Evaluation of the outcome after resection for distal bile duct cancer (DBC) with focus on the impact of microscopic histopathological resection status R0 (>1 mm) versus R1 (≤1 mm) vs R1 (direct).

DBC is a rare disease for which oncologic resection offers the only chance of cure.

Prospectively collected data of consecutive patients undergoing pancreaticoduodenectomy for DBC were analyzed. Histopathological resection status was classified according to the Leeds protocol for pancreatic ductal adeno carcinoma (PDAC) (PDAC; R0 >1 mm margin clearance vs R1 ≤1 mm vs R1 direct margin involvement).

A total of 196 patients underwent pancreaticoduodenectomy for DBC. Microscopic complete tumor clearance (R0>1 mm) was achieved in 113 patients (58%). Median overall survival (OS) of the entire cohort was 37 months (5- and 10-year OS rate: 40% and 31%, respectively). After R0 resection, median OS increased to 78 months with a 5-year OS rate of 52%. Negative prognostic factors were age >70 years ( P < 0.0001, hazard ratio (HR) 2.48), intraoperative blood loss >1000 mL ( P = 0.0009, HR 1.99), pN1 and pN2 status ( P = 0.0052 and P = 0.0006, HR 2.14 and 2.62, respectively) and American Society of Anesthesiologists score >II ( P = 0.0259, HR 1.61).

This is the largest European single-center study of surgical treatment for DBC and the first to investigate the prognostic impact of the revised PDAC resection status definition in DBC. The results show that this definition is valid in DBC and that "true" R0 resection (>1 mm) is a key factor for excellent survival. In contrast to PDAC, there was no survival difference between R1 (≤1 mm) and R1 (direct).

Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise.

Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death.

Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT.

For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.

The impact of lymph node metastasis on survival in pancreatic neuroendocrine neoplasms as well as their best surgical treatment is controversial. We aimed to determine the frequency and prognostic impact of lymph node involvement in pancreatic neuroendocrine neoplasms.

Patients undergoing pancreatic resections for pancreatic neuroendocrine neoplasms between 2001 and 2019 were retrospectively analyzed based on a prospective database. Clinicopathological parameters and perioperative outcome were assessed. Overall and disease-free survival was analyzed. Subgroup analysis was performed for sporadic, nonfunctional pancreatic neuroendocrine neoplasms without distant metastases and ≥4 analyzed lymph nodes.

Of 605 surgically resected pancreatic neuroendocrine neoplasms, 55% were G1, 36% were G2, and 9% were G3 differentiated. At the time of resection, 34% of patients had lymph node metastasis, and 16% had distant metastases. For subgroup analysis, 314 patients were analyzed. Lymph node metastases occurred in 36% of patients and were most frequent in G3 patients (67%). An increase in tumor size and advancement was associated with higher rates of lymph node metastasis, and disease-free survival was significantly impaired. Significant differences in disease-free survival were observed between 1 and 3 (5-year disease-free survival 52%) and ≥4 positive lymph nodes (5-year disease-free survival 28%), as well as when G3 tumors were excluded. In multivariable analysis, grading, tumor stage, and especially lymph node metastases as well as the proposed pN1 and pN2 categories were confirmed as independent predictors of recurrence.

The presence and extent of lymph node involvement has considerable prognostic impact in pancreatic neuroendocrine neoplasms. This study, for the first time, validated the proposed pN2 stage for well-differentiated pancreatic neuroendocrine neoplasms.

The aim of this study was to develop and validate a pretreatment prognostic score in pancreatic cancer (PDAC).

Pretreatment prognostication in PDAC is important for treatment decisions but remains challenging. Available prognostic tools are derived from selected cohorts of patients who underwent resection, excluding up to 20% of patients with exploration only, and do not adequately reflect the pretreatment scenario.

Patients undergoing surgery for PDAC in Heidelberg from July 2006 to June 2014 were identified from a prospective database. Pretreatment parameters were extracted from the database and the laboratory information system. Parameters independently associated with overall survival by uni- and multivariable analyses were used to build a prognostic score. A contemporary cohort from Verona was used for external validation.

In 1197 patients, multiple pretreatment parameters were associated with overall survival by univariable analyses. American Society of Anesthesiology classification, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, C-reactive protein, albumin, and platelet count were independently associated with survival and were used to create the Heidelberg Prognostic Pancreatic Cancer (HELPP)-score. The HELPP-score was closely associated with overall survival (median survival between 31.3 and 4.8 months; 5-year survival rates between 35% and 0%) and was able to stratify survival in subgroups with or without resection as well as in CA19-9 nonsecretors. In the resected subgroup the HELPP-score stratified survival independently of pathological prognostic factors. The HELPP-score was externally validated and was superior to CA19-9 in both the development and validation cohorts.

The HELPP-score is a readily available prognostic tool based on pretreatment routine parameters to stratify survival in PDAC independently of resection status and pathological tumor stage.

The aim of this study was to reappraise the optimal number of examined lymph nodes (ELNs) in pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).

The well-established threshold of 15 ELNs in PD for PDAC is optimized for detecting 1 positive node (PLN) per the previous 7th edition of the American Joint Committee on Cancer (AJCC) staging manual. In the framework of the 8th edition, where at least 4 PLN are needed for an N2 diagnosis, this threshold may be inadequate for accurate staging.

Patients who underwent upfront PD at 2 academic institutions between 2000 and 2016 were analyzed. The optimal ELN threshold was defined as the cut-point associated with a 95% probability of identifying at least 4 PLNs in N2 patients. The results were validated addressing the N-status distribution and stage migration.

Overall, 1218 patients were included. The median number of ELN was 26 (IQR 17-37). ELN was independently associated with N2-status (OR 1.27, P < 0.001). The estimated optimal threshold of ELN was 28. This cut-point enabled improved detection of N2 patients and stage III disease (58% vs 37%, P = 0.001). The median survival was 28.6 months. There was an improved survival in N0/N1 patients when ELN exceeded 28, suggesting a stage migration effect (47 vs 29 months, adjusted HR 0.649, P < 0.001). In N2 patients, this threshold was not associated with survival on multivariable analysis.

Examining at least 28 LN in PD for PDAC ensures optimal staging through improved detection of N2/stage III disease. This may have relevant implications for benchmarking processes and quality implementation.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.

Evaluated lymph node (ELN) yield has been established as a promising measure of surgical quality. Research has suggested that an ELN of at least 15 in pancreatic cancer patients is associated with improved survival and staging metrics. The aim of this study was to determine what impact a high ELN yield of ≥15 has in a novel population.

A retrospective cohort study was performed of patients with resectable, non-metastatic pancreatic adenocarcinoma who underwent neoadjuvant therapy followed by pancreatectomy using the National Cancer Database (NCDB 2004-2017). Patients who had <15 nodes examined and those who had ≥15 examined (high ELN) were compared. Univariate and multivariate analyses were performed to determine factors associated with ELN yield. A Cox proportional hazards model was used to identify factors associated with overall survival.

A total of 5,930 patients were included; 58% of patients had ≥15 lymph nodes examined. High ELN was associated with significant improvement in overall survival rates (p<0.004) and perioperative outcomes including post-operative stay (p<0.0001), 30-day unplanned readmission (p<0.028), and 90-day mortality (p<0.001). Patients who were treated at facilities with a high procedure-specific surgery volume were more likely to receive high ELN surgeries than those treated at facilities with a low volume (HR = 2.86[95% CI = 2.36-3.47]).

An ELN yield of ≥15 was a significant measure of surgical quality in this novel population as it was associated with improvements in survival and perioperative outcomes. However, considerable harvest disparities exist at the facility level.

The nodal stage of pancreatic ductal adenocarcinoma (PDAC) is revised in the AJCC 8th edition. Studies on the prognosis of PDAC according to lymph node metastasis (LNM) are still ongoing. We attempted to find the patterns of nodal involvement and to reveal its clinical significance to overall survival (OS).

We analyzed 585 patients who received pancreatic head cancer surgery diagnosed as PDAC from January 2007 to December 2016. Patients were classified into three groups: Group 1 (G1, patients without LNM), Group 2 (G2, those with LNM only in the peripancreatic area), and Group 3 (G3 those with LNM in the other area and/or peripancreatic LNM). Risk factors were analyzed by Cox-regression test and overall survival was compared by Kaplan-Meier analysis.

LNM in peripancreatic area was the most common (88.7%). In the multivariate analysis, T stage, nuclear differentiation, adjuvant treatment, and the G2 and G3 were independent risk factors for OS (G2 over G1, HR 1.384, 95% CI 1.046-1.802; P = .036 and G3 over G1, HR 2.383, 95% CI 1.378-4.103; P = .001). G3 showed worse OS than G2 (P = .006). In the N1 status, LNM to the pericholedochal (PC) and superior mesenteric artery (SMA) areas resulted in worse OS than the G2 (P = .011 and P = .019).

We found that LNM beyond the peripancreatic area significantly affects OS in pancreatic head cancer patients. Depending on the station of the LNM, different risk-stratification and treatment strategies will need to be considered.

The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications.

Patients who underwent pancreatic ductal adenocarcinoma resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan-Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS).

Overall, 750 patients with a median OS of 18 months (interquartile range 10-32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56-0.61) vs. 0.56 (95% CI 0.54-0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80-2.09; p  = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75-1.83; p  = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59-0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p  < 0.05).

The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.

The appropriate extent of lymphadenectomy for pancreatic cancer of the body/tail has not been standardized worldwide. The present study evaluated the optimal extent of harvesting lymph nodes.

Patients who underwent distal pancreatectomy for invasive ductal carcinoma of the pancreas between 2007 and 2018 were retrospectively reviewed. Patients were subclassified into three groups depending on the tumor location: pancreatic body (Pb), proximal pancreatic tail (Ptp), and distal pancreatic tail (Ptd). The pancreatic tail was further divided into even sections of Ptp and Ptd. Patterns of lymph node metastasis and the impact of lymph node metastasis on the prognosis were examined.

A total of 120 patients were evaluated. Fifty-eight patients had a tumor in the Pb, 38 in the Ptp, and 24 in the Ptd. No patients with a Ptd tumor had metastasis beyond the peripancreatic and splenic hilar lymph nodes (LN-PSH). All patients with metastasis to the lymph nodes along the common hepatic artery (LN-CHA) or along the left lateral superior mesenteric artery (LN-SMA) also had metastasis to the LN-PSH. Recurrence after surgery occurred significantly earlier in this population. In a multivariate analysis, metastasis to the LN-CHA or LN-SMA (hazard ratio [HR] 3.3; P = .04) was an independent risk factor for overall survival. Furthermore, high levels of preoperative serum CA19-9 (HR 10.9; P = .013) were a predictive factor for metastasis to the LN-CHA or LN-SMA.

Metastasis to the LN-CHA or LN-SMA was rare but a significant prognostic factor in patients with pancreatic body/tail cancer.

Implementing a prospective lymphadenectomy protocol, we investigated the nodal yields and metastases per anatomical stations and nodal echelon following upfront pancreatoduodenectomy (PD) for cancer. Next, the relationship between the extension of nodal dissection, the number of examined and positive nodes (ELN/PLN), disease staging and prognosis was assessed.

Lymphadenectomy included stations 5, 6, 8a-p, 12a-b-p, 13, 14a-b, 17, and jejunal mesentery nodes. Data were stratified by N-status, anatomical stations, and nodal echelons. First echelon was defined as stations embedded in the main specimen and second echelon as stations sampled as separate specimens. Recurrence and survival analyses were performed by using standard statistics.

Overall, 424 patients were enrolled from June 2013 through December 2018. The median number of ELN and PLN was 42 (interquartile range [IQR] 34-50) and 4 (IQR 2-8). Node-positive patients were 88.2%. The commonest metastatic sites were stations 13 (77.8%) and 14 (57.5%). The median number of ELN and PLN in the first echelon was 28 (IQR 23-34) and 4 (IQR 1-7). While first-echelon dissection provided enough ELN for optimal nodal staging, the aggregate rate of second-echelon metastases approached 30%. Nodal-related factors associated with recurrence and survival were N-status, multiple metastatic stations, metastases to station 14, and jejunal mesentery nodes.

First-echelon dissection provides adequate number of ELN for optimal staging. Nodal metastases occur mostly at stations 13/14, although second-echelon involvement is frequent. Only station 14 and jejunal mesentery nodes involvement was prognostically relevant. This latter station should be included in the standard nodal map and analyzed pathologically.

Intraductal papillary mucinous neoplasm (IPMN)-associated carcinoma is a subtype of pancreatic cancer for which prognostic factors, the validity of the AJCC/UICC staging system and the role of adjuvant chemotherapy remain unknown.

Clinicopathological, treatment and follow-up data of patients with IPMN-associated carcinoma undergoing resection between 2002 and 2018 were analyzed. Uni- and multivariable survival analyses were performed to identify prognostic factors.

Of 424 patients undergoing resection for IPMN-associated carcinoma, 77% patients had pancreatic ductal adenocarcinoma (IPMN-PDAC) and 23% had colloid carcinoma (IPMN-CC). Compared to IPMN-CC, IPMN-PDAC was diagnosed at more advanced tumor stages, more frequently involved lymph nodes, more frequently showed poor differentiation and were associated with higher rates of R1 resections. Resected IPMN-PDAC showed markedly shorter median overall survival than IPMN-CC (26.7 months vs. 91.3 months). The current AJCC/UICC staging system was validated for IPMN-associated carcinoma and for both of its subtypes. In multivariable analysis age ≥70 years, diabetes mellitus, high levels of Ca 19-9, IPMN-PDAC subtype, G3 tumors and higher AJCC/UICC stage were independently associated with shorter survival. Adjuvant therapy was not associated with improved survival in IPMN-associated carcinoma. Overall survival was comparable in patients receiving vs. not receiving adjuvant therapy.

Survival after resection of IPMN-associated carcinoma depends on tumor stage, on histologic tumor subtype, grading, and Ca 19-9 levels. The current 8th edition of the AJCC/UICC staging system is applicable for IPMN-associated carcinoma and for both of its subtypes IPMN-PDAC and IPMN-CC. The role of adjuvant therapy for IPMN-associated carcinoma remains unclear.