Prognostic impact of simultaneous venous resections during surgery for resectable pancreatic cancer

BackgroundThe aim of this study was to evaluate the prognostic impact of simultaneous venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) that was preoperatively staged resectable according to NCCN guidelines.MethodsA retrospective analysis of 153 patients who underwent PD for PDAC was performed. Patients were divided into standard PD and PD with simultaneous vein resection (PDVR). Groups were compared to each other in terms of postoperative morbidity and mortality, disease free (DFS) and overall survival (OS).Results114 patients received PD while 39 patients received PDVR. No differences in terms of postoperative morbidity and mortality between both groups were detected. Patients in the VR group presented with a significantly shorter OS in the median (13 vs. 21 months, P = 0.011). In subgroup analysis, resection status did not influence OS in the PDVR group (R0 13 vs. R1 12 months, P = 0.471) but in the PD group (R0 23 vs. R1 14 months, P = 0.043). PDVR was a risk factor of OS in univariate but not multivariable analysis.ConclusionPDVR for PDAC preoperatively staged resectable resulted in significantly shorter OS regardless of resection status. Patients who require PDVR should be considered for adjuvant chemotherapy in addition to other oncological indications.     

Survival impact of distal pancreatectomy with en bloc celiac axis resection combined with neoadjuvant chemotherapy for borderline resectable or locally advanced pancreatic body carcinoma

BackgroundThe survival benefit associated with distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for patients with borderline resectable or locally advanced pancreatic body carcinoma is controversial. The aim of this study was to evaluate the impact of DP-CAR following neoadjuvant chemotherapy on survival in patients with borderline resectable or locally advanced pancreatic body carcinoma.MethodsMedical records of patients with pancreatic ductal adenocarcinoma who underwent distal pancreatectomy (DP, n = 102) and DP-CAR following neoadjuvant chemotherapy (n = 32) between 2008 and 2019 were analyzed retrospectively. Short- and long-term outcomes were compared between the two groups.ResultsAll patients who underwent DP-CAR had tumor contact with the celiac axis. Of these, 30 patients underwent preoperative embolization of the common hepatic artery. The pretreatment tumor size of patients who underwent DP-CAR was larger (P < 0.001), and rates of blood transfusion (P = 0.003) and postoperative complications (P = 0.016) were higher in patients who underwent DP-CAR compared with patients who underwent DP. The 5-year survival rate of patients who underwent DP and DP-CAR were 50.6% and 41.1%, respectively (median survival time, 65.9 vs 37.0 months). For all 134 patients, pretreatment serum CA19-9 levels (P < 0.001), adjuvant chemotherapy (P < 0.001), and lymph node status (P = 0.035) were independent prognostic factors of overall survival by multivariate analysis.ConclusionsDP-CAR following neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic body carcinoma may bring the same survival impact as DP, despite increased morbidity.     

Prior history of acute pancreatitis predicts poor survival in patients with resectable pancreatic ductal adenocarcinoma

Background/objectivesMounting evidence has suggested that acute pancreatitis (AP) is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but its role in survival in PDAC patients was rarely investigated. The objective was to investigate the association of a history of AP with survival among PDAC patients who underwent surgical resection.MethodsA retrospective cohort study comprising 632 patients who were diagnosed with resectable PDAC was conducted. Survival was evaluated by history of AP prior to a diagnosis of PDAC using Kaplan-Meier methods and log-rank tests. Multivariate analyses for mortality were estimated using the Cox proportional hazards model. Propensity score matching methods were used to balance the difference of clinical characteristics between patients with and without AP history.ResultsThe log-rank tests showed that patients with a history of AP had a worse overall survival than those without a history of AP (p = 0.006). The multivariable-adjusted hazard ratio (HR) for mortality comparing participants with AP to those without AP was 1.808 (95% CI: 1.241–2.632, p = 0.002). Patients with a recent history of AP (<2 years), rather than patients with a remote history of AP (≥2 years), were found to have significantly worse survival (p = 0.014) than those without a history of AP. After adjusted for PSM, history of AP remained an independent survival predictor of PDAC following surgical resection.ConclusionsOur findings indicate that a history of AP, especially a recent history of AP, is associated with poor survival among patients with resectable pancreatic ductal adenocarcinoma.     

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

The risk of not receiving adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: a nationwide analysis

BackgroundThe relation between type of postoperative complication and not receiving chemotherapy after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim was to investigate which patient factors and postoperative complications were associated with not receiving adjuvant chemotherapy.MethodsPatients who underwent resection (2014–2017) for PDAC were identified from the nationwide mandatory Dutch Pancreatic Cancer Audit. The association between patient-, tumor-, center-, treatment characteristics, and the risk of not receiving adjuvant chemotherapy was analyzed with multivariable logistic regression.ResultsOverall, of 1306 patients, 24% (n = 312) developed postoperative Clavien Dindo ≥3 complications. In-hospital mortality was 3.5% (n = 46). Some 433 patients (33%) did not receive adjuvant chemotherapy. Independent predictors (all p < 0.050) for not receiving adjuvant chemotherapy were older age (odds ratio (OR) 0.96), higher ECOG performance status (OR 0.57), postoperative complications (OR 0.32), especially grade B/C pancreatic fistula (OR 0.51) and post-pancreatectomy hemorrhage (OR 0.36), poor tumor differentiation grade (OR 0.62), and annual center volume of <40 pancreatoduodenectomies (OR 0.51).ConclusionsThis study demonstrated that a third of patients do not receive chemotherapy after resection of PDAC. Next to higher age, worse performance status and lower annual surgical volume, this is mostly related to surgical complications, especially postoperative pancreatic fistula and post-pancreatectomy hemorrhage.     

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma

Background/Objectives: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC).MethodsNinety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined.ResultsThe low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19–9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC.ConclusionsLow mitochondrial OGG1 expression might aggravate the PDAC prognosis.     

Focal pancreatic parenchyma atrophy is a harbinger of pancreatic cancer and a clue to the intraductal spreading subtype

Background/ObjectivesRadiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis.MethodsData on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC.ResultsFPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P < 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16–63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved.The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P < 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia.ConclusionsFPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.     

Prognostic impact of intraoperative peritoneal cytology after neoadjuvant therapy for potentially resectable pancreatic cancer

BackgroundNeoadjuvant therapy (NAT) is considered a potential approach to improve survival for patients with pancreatic adenocarcinoma (PA). The objective of this study was to identify the clinical implications of washing peritoneal cytology (CY) status after NAT.MethodsBetween 2005 and 2016, 151 consecutive patients with resectable (R)/borderline resectable (BR) PA underwent NAT with intention of subsequent resection at our institution. Of them, 13 and 123 patients underwent pancreatectomies with positive (CY+) and negative (CY-) cytology, respectively, while the remaining 15 patients did not undergo resection due to gross metastases at laparotomy. The clinicopathological factors influencing overall survival were clarified by the uni- and multivariate analyses.ResultsThe postoperative overall survival (OS) and disease-free survival (DFS) were markedly worse in patients who underwent resection with CY+, compared with those who were CY- (median OS, 14.8 m vs 30.8 m, p = 0.026, and median DFS 6.0 m vs 15.1 m, p = 0.008). According to the resectability by NCCN guidelines, CY+ indicates worse prognosis than CY- in R-PA patients (mOS: 30.1 m vs 71.1 m: p = 0.080). Similarly, in BR-PA patients, CY+ showed the significantly worse prognosis than CY- (mOS: 13.8 m vs 24.5 m: p = 0.048), which prognosis is comparable with patients who did not undergo resection. The multivariate analysis revealed that resectability, CY status and the induction of adjuvant therapy were significant predictors of postoperative OS (p = 0.007: Hazard ratio 2.264, 0.040:2.094 and 0.002:3.246, respectively).ConclusionsCY+ is a significant predictor of poorer prognosis in PA patients after NAT. The subsequent pancreatectomies with CY+ after NAT do not contribute to prolonged survival.     

Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma

Background/Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications.MethodsTwenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences.ResultsOf the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and β-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01).ConclusionsThe diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.     

Chronological improvement of pancreatectomy for resectable but advanced pancreatic neuroendocrine neoplasms

BackgroundProgress of non-surgical treatments in the last decade has improved the prognosis of pancreatic neuroendocrine neoplasms (PanNEN). However, the improvement of surgery for advanced PanNEN remains unknown. This study aimed to investigate the chronological changes of the clinical impact of pancreatectomy for PanNEN.MethodsPatients undergoing curative-intent pancreatectomy for PanNEN between 1991 and 2010 were categorized into the earlier period group, and those between 2011 and 2021 were into the later period group.Advanced PanNEN was defined as showing resectable synchronous liver metastases or invasion to portal venous systems or adjacent organs. The recurrence-free survival (RFS) and overall survival (OS) were analyzed among patients with non-advanced and advanced PanNENs. The independent prognostic risk factors were identified using a Cox proportional hazard model.ResultsA total of 189 patients (n = 54 in the earlier period and n = 135 in the later period) were included. The proportion of advanced PanNEN increased from 15% to 30% (P = 0.027). The RFS and OS of non-advanced PanNEN were similar between the periods. Whereas, among patients with advanced PanNEN, the later period group showed improved prognosis; The 5-year RFS of the earlier period vs. the later period was 0% vs. 27%, and the 5-year OS was 38% vs. 82% (p = 0.013).ConclusionsA radical surgical treatment for advanced PanNEN has shown prognostic improvement in this decade. However, more careful perioperative examinations and possibly, additional treatments are required for PanNEN with portal vein invasion.     

Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer

BackgroundWe evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers.MethodsMaterials were derived from the prospective nationwide Dutch Pancreas Biobank (2015–2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.ResultsMedian ADAM12 levels were 161 (IQR 79–352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87).ConclusionHigh circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.     

Patients with hepatic oligometastatic pancreatic body/tail ductal adenocarcinoma may benefit from synchronous resection

BackgroundSynchronous resection of primary pancreatic ductal adenocarcinoma (PDAC) and liver metastases in highly selective patients is being accepted based on oncology research progress showing safe surgical outcomes with low morbidity and mortality. We also tried to determine patients who would benefit from the operation.MethodsFrom January 2012 to October 2017, 48 patients who underwent synchronous resection of primary PDAC and liver metastases were retrospectively evaluated. Twenty-three of them underwent oligometastatic synchronous resection.ResultsThe majority of synchronous resection PDAC patients underwent hepatic wedge resection, and no oligometastatic patient was treated with hemihepatectomy. The median overall survival (OS) of the synchronous resection patients was 7.8 months. Hepatic oligometastatic PDAC patients had a longer OS than that of non-oligometastatic synchronous resection patients, systemic chemotherapy patients and palliative patients (16.1 vs 6.4 months, P = 0.02; 16.1 vs 7.6 months, P = 0.02; 16.1 vs 4.3 months, P < 0.0001; respectively). Further analysis showed that localized pancreatic body/tail PDAC had a better OS in oligometastatic patients than in non-oligometastatic synchronous resection patients (16.8 months vs 7.05 months, P = 0.0004) and systemic chemotherapy patients (16.8 months vs 8 months, P = 0.003).ConclusionPatients with pancreatic body/tail PDAC with liver oligometastases can benefit from synchronous resection.     

Completion of adjuvant therapy in patients with resected pancreatic cancer

BackgroundAdjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC). It is estimated that only 40–80% eligible patients initiate intended adjuvant chemotherapy. Completion rates are largely unknown.MethodsA retrospective analysis of outcomes of patients with resected PDAC over an 8-year period at H. Lee Moffitt Cancer Center (MCC) was performed.ResultsFrom a total of 309 patients, 299 were included for further analysis. 242 (81%) initiated adjuvant therapy (AT) and 195 (65%) completed the intended course. The median time-to-initiation of AT was 53 days (7.6 weeks). The most common reasons for early discontinuation of AT (n = 47) were toxicity (n = 29), disease recurrence (n = 9), patient decision (n = 4), unrelated comorbidities (n = 3), and death (n = 1). Completion of AT was an independent predictor of overall survival (OS) and recurrence-free survival (RFS) on multivariable analysis (OS: HR 0.41, CI 0.27–0.61, p < 0.001; RFS: HR 0.52, CI 0.36–0.76, p < 0.001). Factors associated with early termination of AT were vascular resection (OR 0.29, CI 0.13–0.67, p = 0.004) and administration of AT with local oncologist as opposed to MCC (OR 0.41, CI 0.21–0.82, p = 0.010).ConclusionCompletion of AT is associated with improved survival in patients with resected PDAC. Factors associated with an inability to complete AT include vascular resection and administration of AT with local care team in the patient's community.     

Post-adjuvant chemotherapy CA19-9 levels predict prognosis in patients with pancreatic ductal adenocarcinoma: A retrospective cohort study

BackgroundCarbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC.MethodsA total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL.ResultsMedian RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p < 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p < 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was >1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value.ConclusionsThe present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.     

Comparing prognostic factors of Glut-1 expression and maximum standardized uptake value by FDG-PET in patients with resectable pancreatic cancer

BackgroundThis study aimed to assess the prognostic values of preoperative maximum standardized uptake value (SUVmax) of primary pancreatic tumors and Glut-1 expression in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC), and to investigate whether Glut-1 expression is more effective than SUVmax in predicting survival in patients with R-PDAC.MethodsWe investigated 101 R-PDAC patients who underwent pancreatectomy for pancreatic cancer treatment. SUVmax analyzed through ¹⁸F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT), and Glut-1 expression, were assessed for predicting the prognosis of patients with R-PDAC.ResultsIn patients with R-PDAC, the high SUVmax group (≥4.25) had significantly shorter overall survival (OS) and disease-free survival (DFS) than the low SUVmax group (＜4.25). Surprisingly, Glut-1 expression was not significantly correlated with SUVmax. Moreover, the high Glut-1 expression group, which was related to higher levels of CA 19–9, had significantly shorter OS and DFS than the low Glut-1 expression group. Furthermore, among the high SUVmax group, OS and DFS were significantly shorter in the high Glut-1 expression group. Multivariate analyses revealed that Glut-1 overexpression was an independent prognostic factor in patients with R-PDAC. Glut-1 knockdown also induced cell cycle arrest in PDAC cells in vitro.ConclusionsThe study determined that Glut-1 overexpression is a more powerful prognostic factor than SUVmax for predicting OS and higher risk of recurrence in R-PDAC patients. Glut-1 overexpression is also more likely to be associated with malignant activity in PDAC patients.     

Preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after curative intent surgical resection

Background: Postoperative early recurrence(ER) in patients with pancreatic ductal adenocarcinoma(PDAC) is frequently encountered after curative intent surgery. Nonetheless, clinical significance and risk factors of ER after surgery for PDAC have not been extensively investigated. The aim of this study was to determine preoperative risk predictors for ER in patients with PDAC after upfront surgery. Methods: Eighty-one consecutive patients with PDAC who underwent curative intent surgical resection at Kangbuk Samsung Hospital between January 2004 and May 2015 were enrolled. ER was defined as tumor relapse within 6 months after surgery. Results: ER occurred in 26 patients(32.1%), whereas 49 patients(60.5%) had late recurrence( ≥ 6 months after surgery), and 6 patients had no recurrence(7.4%). Univariate analysis showed that C-reactive protein(CRP) 3.0 mg/dL, modified Glasgow prognostic score(mGPS) = 2, decrease of total lymphocyte count by 50% of baseline value in the preoperative period, prognostic nutritional index(PNI) 45, neutrophilto-lymphocyte ratio(NLR) ≥ 3, and preoperative maximum standardized uptake value(SUVmax) were significantly associated with ER. Multivariate logistic regression analysis revealed that CRP 3.0 mg/dL, decrease of total lymphocyte count by 50% of baseline value, and preoperative SUVmax were significant and independent contributors of ER in patients with resectable PDAC who underwent curative intent surgery. Conclusions: Postoperative ER for resectable PDAC was frequent with poor prognosis after curative intent upfront surgery. It is reasonable to suggest that there is a subgroup of resectable PDAC patients at highrisk of ER and neoadjuvant therapy should be considered in these patients in a clinical trial setting.     

The combination of systemic inflammation-based marker NLR and circulating regulatory T cells predicts the prognosis of resectable pancreatic cancer patients

BackgroundThe systemic inflammation response and immune impairment are closely related to the development and progression of various tumours, such as pancreatic cancer. In this study, we evaluated circulating inflammation factors and circulating regulatory T cells (Tregs) as markers of immunosuppression in a cohort of Chinese patients with resectable pancreatic cancer.MethodsSamples were retrospectively collected from a series of 195 pathological stage I/II pancreatic cancer patients who underwent potentially curative surgery between June 2010 and April 2014. To examine the prognostic factors, circulating systemic inflammation-based markers and Tregs, detected by flow cytometry, were analysed.ResultsUnivariate analyses revealed that the neutrophil-lymphocyte ratio (NLR), TNM stage, differentiation, chemotherapy, CA19-9 levels and presence of Tregs are significantly associated with overall survival in patients with resectable pancreatic cancers. NLR (p = 0.001, HR = 0.538), TNM stage (p = 0.004, HR = 0.593), differentiation (p = 0.011, HR = 0.46), chemotherapy (p = 0.006, HR = 0.516) and Tregs (p = 0.001, HR = 0.558) are identified as independent prognostic markers by multivariate analyses. Interestingly, we also found that high NLR levels combined with a high proportion of Tregs (p < 0.001, HR = 3.521) correlate strongly with worse survival, with a greater than 3.5–fold increased risk of death compared with those with concurrent low levels of NLR and Tregs.ConclusionsThe preoperative NLR and circulating regulatory T cells are potentially independent prognostic factors for overall survival in resectable pancreatic cancer patients. High NLR levels combined with poor immune state before surgery, as measured by Tregs, are associated with an extremely poor prognosis.     

The impact of extent of pancreatic and venous resection on survival for patients with pancreatic cancer

BackgroundBorderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins, especially in the case of up-front resections, but it is important to know the limits of surgical therapy in this disease. This study aimed to investigate the impact of extent of pancreatic and venous resection on short- and long-term outcomes in patients with pancreatic adenocarcinoma (PDAC).MethodsThis was a retrospective study from a prospectively maintained database of pancreatic resections for PDAC. Short- and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy (TP) or pancreaticoduodenectomy (PD) with simultaneous portal vein (PV) and/or superior mesenteric vein (SMV) resection. Venous resections were carried out as tangential venous resection (TVR) or segmental venous resection (SVR). Patients were divided into 4 groups: (1) PD + TVR, (2) PD + SVR, (3) TP + TVR, (4) TP + SVR. Uni- and multivariate Cox regression analysis were performed to identify factors associated with survival.ResultsNinety-nine patients were submitted to simultaneous pancreatic and venous resection for PDAC. Among them, 25 were submitted to PD + TVR (25.3%), 12 to PD + SVR (12.1%), 23 to TP + TVR (23.2%), and 39 to TP + SVR (39.4%). Overall, major morbidity (Clavien-Dindo grade ≥ IIIA) was 26.3%. Thirty- and 90-day mortality were 3% and 11.1%, respectively. There were no significant differences among groups in terms of short-term outcomes. Median overall survival of patients submitted to PD + TVR was significantly higher than those to TP+SVR (29.5 vs 7.9 months, P = 0.001). Multivariate analysis identified TP (HR = 2.11; 95% CI: 1.31–3.44; P = 0.002) and SVR (HR = 2.01; 95% CI: 1.27–3.15; P = 0.003) as the only independent prognostic factors for overall survival.ConclusionsUp-front TP associated to SVR was predictive of worse survival in borderline resectable PDAC. Perioperative treatments in high-risk surgical groups may improve such poor outcomes.     

Clinical characteristics of initial recurrence in lung after surgical resection for pancreatic ductal adenocarcinoma

BackgroundThe clinical characteristic differences at the initial recurrence site after resection for pancreatic ductal adenocarcinoma (PDAC) remain unknown. We investigated the clinical characteristics in patients with lung recurrence after surgical resection and evaluated the outcome of resection for isolated lung recurrence.MethodsOf 442 consecutive PDAC patients who underwent surgical resection between 2002 and 2018, 229 had recurrence on imaging. Initial recurrence sites were the liver, lung, local, peritoneal, multiple organs, and others. We analyzed the clinicopathologic factors and outcomes, comparing by initial recurrence site, and investigated the outcomes of resection for isolated lung recurrence.ResultsLiver recurrences were the most frequent (n = 60, 26%), followed by lung recurrence (n = 48, 21%). The interval from surgery to recurrence was significantly longer in lung recurrence (P = 0.0001). Patients with lung recurrence had significantly longer overall survival after diagnosis (P < 0.0001). Patients who underwent surgical resection of lung recurrence had a significantly prolonged overall survival rate after recurrence diagnosis (P = 0.004).ConclusionsPatients with lung recurrence had significantly prolonged survival than those with other recurrence patterns. Resection for isolated lung recurrence represented relatively good prognosis, and possibly may be beneficial in highly-selected patients.