Preoperative evaluation of pancreatic ductal adenocarcinoma with synchronous liver metastasis: Diagnosis and assessment of unresectability

AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma(PDAC) and assess unresectability of synchronous liver metastasis.METHODS Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group.RESULTS CA125 38 U/mL(OR = 12.397, 95%CI: 5.468-28.105, P 0.001) and diabetes mellitus(OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 62 U/mL(OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age 62 years(OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with postoperatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels(7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone(7.0 mo vs 16.9 mo, P 0.001), with no higher rates of either pancreatic fistula(P = 0.072) or other complications(P = 0.230) and no greater impacts on length of hospital stay(P = 0.602) or post-operative diabetic control(P = 0.479).CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.     

Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma

BackgroundThe clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined.ObjectiveTo assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC.MethodsThe study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis.ResultsAmong all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR.ConclusionspCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.     

Prognostic impact of the ratio of preoperative CA19-9 to liver enzyme levels in pancreatic cancer patients with jaundice (predictability of combined CA19-9/AST and CA19-9/γ-GGT for jaundiced PDAC patients)

BackgroundCarbohydrate antigen 19–9 (CA19-9) has been reported as the most significant survival predictor of patients with pancreatic ductal adenocarcinoma (PDAC). However, the elevation of CA19-9 could interfere with obstructive jaundice and the predictive value of CA19-9 in PDAC patients with jaundice remains to be analyzed and elucidated to find possible adjustments.ObjectiveTo evaluate the predictability of preoperative CA19-9 and its adjustments for the overall survival (OS) of PDAC patients by analyzing the relationship between preoperative serum CA19-9 and total bilirubin (TBIL).MethodsA total of 563 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma in our center between January 2015 and September 2018 were retrospectively reviewed. Clinicopathologic information was collected and preoperative parameters such as CA19-9, CEA, TBIL, γ-GGT, AST, ALT, and ALP were recorded as well as overall survival rates, which began from the date of operation to that of death or the last follow-up. Kaplan-Meier survival curves with log-rank test and Cox regression models were applied using SPSS and the survival and survminer packages in R software.ResultsUsing 39/390/1000 as the cut-off values for preoperative serum CA19-9, significant capability of OS stratification was found in the total cohort (p < 0.001, MST = 29.7/19.1/15.2/12.1 months) and patients with TBIL <102.6 μmol/L (p < 0.001, MST = 32.2/19.6/15.0/11.2 months). However, in the subgroup of TBIL≥102.6 μmol/L, this classification method was replaced by the combined scoring of CA19-9/AST and CA19-9/γ-GGT.ConclusionsAs an independent predictor of overall survival of PDAC patients, preoperative serum CA19-9 is defective in survival stratification when TBIL≥102.6 μmol/L but a positive survival prognosis could be achieved with the application of combined preoperative CA19-9/AST and CA19-9/γ-GGT.     

Serum cytokine profiles in patients with pancreatic cancer and chronic pancreatitis

BackgroundChronic pancreatitis (CP) may cause tumor-like lesions, creating a challenge in distinguishing between CP and pancreatic ductal adenocarcinoma (PDAC) in a patient. Given that invasive surgery is a standard cancer treatment, we aimed to examine whether a noninvasive diagnostic tool utilizing serum cytokines could safely differentiate between PDAC and CP.MethodsA pre-operative serum panel comprising 48 inflammatory cytokines, CA19-9, and C-reactive protein (CRP) was analyzed, consisting of 231 patients, 186 with stage I–III PDAC and 45 with CP. We excluded PDAC patients who underwent neoadjuvant therapy and those CP patients with other active malignancies. The laboratory variables most associated with PDAC diagnosis were assessed using logistic regression and selected using the lasso method.ResultsThe cytokines CTACK, GRO-α, and β-NGF were selected alongside CA19-9 and CRP for our differential diagnostic model. The area under the curve (AUC) for our differential diagnostic model was 0.809 (95% confidence interval [CI] 0.738–0.880), compared with 0.791 (95% CI 0.728–0.854) for CA19-9 alone (not significant).ConclusionsWe found that inflammatory cytokines CTACK, GRO-α, and β-NGF alongside CA19-9 and CRP may help distinguish PDAC from CP.     

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.     

GRP78 expression and prognostic significance in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant therapy versus surgery first

BackgroundGlucose-regulated protein 78 (GRP78) plays an essential role in protein folding, transportation, and degradation, thus regulates ER homeostasis and promotes cell survival, proliferation and invasion. GRP78 expression in PDAC patients who received neoadjuvant therapy has not been reported.MethodsThis retrospective study of resected PDAC patients included 125 patients treated with neoadjuvant therapy (NAT) and 140 patients treated with surgery first (SF). The expression of GRP78 was evaluated by immunohistochemistry on tissue microarrays and the results were correlated with clinicopathologic parameters and survival.ResultsGRP78 expression was higher in SF patients compared to NAT patients (P < 0.001). In SF cohort, the median disease-free survival (DFS) and overall survival (OS) for patients with GRP78-positive tumors were 11.2 months and 25.0 months, respectively, compared to DFS of 52.1 months (P = 0.008) and OS of 69.5 months (P = 0.02) for those with GRP78-negative tumors. GRP78 expression correlated with higher frequency of recurrent/metastasis (P = 0.045). In NAT cohort, GRP78 expression correlated with shorter OS (P = 0.03), but not DFS (P = 0.08). GRP78 expression was an independent prognosticator for both DFS (P = 0.02) and OS (P = 0.049) in SF cohort and was an independent prognosticator for OS (P = 0.03), but not for DFS (P = 0.06) in NAT cohort by multivariate analysis.ConclusionsOur study showed that GRP78 expression in NAT cohort is lower than that in SF cohort. GRP78 expression correlated with shorter survival in both SF and NAT patients. Our findings suggest that targeting GRP78 may help to improve the prognosis in PDAC patients.     

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.     

SUVmax after (18)fluoro-deoxyglucose positron emission tomography/computed tomography: A tool to define treatment strategies in pancreatic cancer

Background(18)fluoro-deoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) might be a useful tool in the management of pancreatic ductal adenocarcinoma (PDAC).AimsThe aim of this study was to analyze maximum standard uptake value (SUVmax) after 18FDG-PET/CT as predictor of survival outcomes and method to determine treatment strategies.MethodsA consecutive series of patients who underwent preoperative 18FDG-PET/CT and subsequent resection for PDAC were retrospectively reviewed. Patients who underwent neoadjuvant chemotherapy were excluded.Results46 patients were included in the analysis. Median follow-up was 27 months (4–67). Patients who recurred within 12 months showed a significantly higher preoperative median SUVmax (8.1 vs 6.1, p = 0.039). Receiver operating characteristics (ROC) curves for disease-free survival (DFS) and disease-specific survival (DSS) identified SUVmax of 6.0 as optimal cut-off. Multivariate analysis showed that SUVmax ≥ 6.0 was an independent predictor of poor DFS (HR 2.288, p = 0.024) and DSS (HR 4.875, p < 0.001). The combination of SUVmax ≥6.0 with CA19.9 ≥200 U/ml was significantly associated with survival outcomes in comparison to patients without concordantly elevated values.ConclusionSUVmax ≥6.0 is an independent predictor of DFS and DSS in resected PDAC. 18FDG-PET/CT might be considered in the preoperative evaluation of patients with pancreatic cancer.     

Induction chemotherapy in pancreatic cancer: CA 19-9 may predict resectability and survival

BackgroundPreoperative/Neoadjuvant treatment (NT) is increasingly used in unresectable pancreatic cancer (PDAC). However, ∼40% of patients cannot be resected after NT and reliable preoperative response evaluation is currently lacking. We investigated CA 19-9 levels and their dynamics during NT for prediction of resectability and survival.MethodsWe screened our institution's database for patients who underwent exploration or resection after NT with gemcitabine-based therapy (GEM) or FOLFIRINOX (FOL). Pre- and post-NT CA 19-9, resection rate and survival were analyzed.ResultsOf 318 patients 165 (51.9%) were resected and 153 (48.1%) received exploration. In the FOL group (n = 103; 32.4%), a post-NT CA 19-9 cutoff at 91.8 U/ml had a sensitivity of 75.0% and a specificity of 76.9% for completing resection with an AUC of 0.783 in the ROC analysis (95% CI: 0.692–0.874; p < 0.001. PPV: 84.2%, NPV: 65.2%). Resected patients above the cutoff did not benefit from resection. Post-NT CA 19-9 <91.8 U/ml (OR 11.63, p < 0.001) and CA 19-9 ratio of <0.4 (OR 5.77, p = 0.001) were independent predictors for resectability in FOL patients.DiscussionCA 19-9 levels after neoadjuvant treatment with FOLFIRINOX predict resectability and survival of PDAC more accurately than dynamic values and should be incorporated into response evaluation and surgical decision-making.     

Survival impact of occult liver metastasis and peritoneal dissemination compared with radiologically defined distant organ metastasis in pancreatic ductal adenocarcinoma

BackgroundCharacteristics and prognoses of patients with occult metastases (OM) of pancreatic ductal adenocarcinoma (PDAC) compared with radiologically defined metastases (RM) have been rarely reported.ObjectiveWe aimed to clarify the prognosis of OM compared with RM and to establish a treatment strategy for PDAC patients with OM.MethodsThis single-institution, retrospective study evaluated patients with unresectable PDAC between 2008 and 2018. OM was defined as abdominal metastasis that was detected by staging laparoscopy or open laparotomy but not in the initial assessment of radiological images.ResultsOM and RM were identified in 135 and 112 patients, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS), neutrophil to lymphocyte ratio (NLR), tumor diameter, and rate of local unresectability were significantly lower in the OM group. Median overall survival (OS) of OM was significantly better than that of RM (13.0 vs 8.9 months, p < 0.001). In multivariate analysis of OS, ECOG PS ≥ 1 (HR 1.64, p = 0.009), NLR ≥5 (HR 1.97, p = 0.004), carbohydrate antigen (CA) 19–9 ≥1000 (HR 1.68, p = 0.001), tumor diameter ≥40 mm (HR 1.40, p = 0.027), conversion surgery (HR 0.12, p < 0.001), and multiple lines of chemotherapy (HR 0.38, p < 0.001) were independent predictors. However, type of metastasis (OM vs RM) not an independent predictor (HR 1.10, p = 0.590).ConclusionThe prognosis of PDAC with OM was relatively better than that with RM, but general and nutritional statuses, primary tumor size and CA19-9, conversion surgery and multiple lines of chemotherapy were independent predictors but not tumor burden.     

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.     

Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

BackgroundThe prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described.MethodsPre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery.ResultsPre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02].ConclusionsAmong patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic.     

Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology

BackgroundCurrent treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are related with overall and early recurrence after pancreatectomy for PDAC.MethodsRetrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence.Results261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3–4 Clavien–Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3–4 Clavien–Dindo complications (OR: 3.05) were independent risk factors for early recurrence.ConclusionAlthough overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.     

The impact of different metastatic patterns on survival in patients with pancreatic cancer

BackgroundThe aims of this study were to compare the metastatic patterns of pancreatic ductal adenocarcinoma (PDAC) of head and body/tail and to determine the prognostic factors.MethodsData of metastatic PDAC (MPC) between 2004 and 2015 from the Surveillance, Epidemiology and End Results (SEER) database was extracted and analyzed. The correlation analyses of metastatic patterns were also conducted. Multivariate Cox regression analyses were used to analyze prognosis.ResultsA total of 27470 eligible MPC patients were collected from SEER database. Patients in the head group had a higher proportion of single-metastasis while those in the body/tail group had a higher proportion of two-site metastases. Similar distributions of metastatic sites were observed in cases with single-metastasis between two groups. Patients with liver and peritoneum metastases in the head group had significantly higher overall survival (OS) rates than those in the body/tail group. Also, the OS rates stratified by varied tumor sites did not differ significantly in patients with bone, brain, and lung metastases. Chemotherapy could prolong survival in almost all MPC patients while radiotherapy or surgery could only benefit certain types of metastases. Tumor site, therapy and vascular invasion were independent prognostic factors of OS in MPC patients.ConclusionsMPC of the head and body/tail presented with different metastatic patterns. Chemotherapy benefited patients with metastases while surgery and radiotherapy could only prolong survival in patients with liver and peritoneum metastases. Our findings may provide more details for the precise management of patients with MPC in clinical practice.     

High level of preoperative carbohydrate antigen 19-9 is a poor survival predictor in gastric cancer

AIM:To assess the clinical significance and the prognostic value of preoperative serum carbohydrate antigen 19-9(CA 19-9)level in gastric cancer.METHODS:Between January 2005 and December2006,1960 patients underwent surgery for histologically confirmed gastric cancer.Of these,163 patients had elevated serum levels of CA 19-9 preoperatively,and1628 patients had normal serum levels of CA 19-9 preoperatively.For this study,325 patients were selected from the group of 1628 patients by age,sex,and cancer stage to serve as controls.Statistically significant differences in survival rates were calculated using the log-rank test.A P value less than 0.05 was considered statistically significant and was determined using SAS software.RESULTS:The baseline characteristics showed some differences between the two groups with regard to histology.Overall survival(OS)in the elevated and nonelevated group was 37.90 and 68.67 mo,respectively(P<0.001).N stage(P=0.001)was a significant predictor of disease-free survival by multivariate analysis.Also,N stage(P<0.001),and the presence of peritoneal metastasis(P<0.001)remained independent factors in predicting OS by multivariate analysis.Additionally,preoperative serum CA 19-9 levels were significantly associated with OS in univariate(P=0.009)and multivariate(P=0.021)analyses.CONCLUSION:Serum CA 19-9 can be considered an independent prognostic factor in predicting OS in patients anticipating surgery for gastric cancer.     

Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis

Background/AimsControversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC.MethodsWe reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 13 propensity score matching (PSM) was performed to reduce selection bias.ResultsCompared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis.ConclusionsWe observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.     

Preoperative Serum CA125 Levels Predict the Prognosis in Hyperbilirubinemia Patients With Resectable Pancreatic Ductal Adenocarcinoma

Serum carbohydrate antigen 19-9 (CA19-9) is widely used to predict the prognosis for pancreatic ductal adenocarcinoma (PDAC). However, hyperbilirubinemia and the CA19-9 nonsecretor phenotype restrict the usage of serum CA19-9 alone. The goal of this study was to confirm the prognostic role of preoperative serum CA125 in PDAC, especially in patients with jaundice.A total of 211 patients with resected PDAC were eligible for this retrospective study, and were classified into 2 groups based on serum bilirubin levels. The prognostic significance of all clinicopathologic factors was evaluated by univariate and multivariate analyses, and the performance of each factor in predicting overall survival (OS) and recurrence-free survival (RFS) was compared.High preoperative CA125, high TNM stage, and lymph node metastasis were independent risk predictors for OS and RFS in all patients and the 2 subgroups, but high CA19-9 was only significant when considering all patients and those with nonelevated bilirubin. Using time-dependent receiver-operating characteristic analysis, better predictive performance for OS and RFS was observed for serum CA19-9 as compared to serum CA125 in these patients.High serum CA125 can independently predict poor prognosis. Importantly, in PDAC patients with hyperbilirubinemia, preoperative serum CA125 can predict the prognosis, whereas CA19-9 cannot. Preoperative CA19-9 had better predictive performance for survival than CA125, and the performance of CA19-9 did not decline between all patients and those with nonelevated bilirubin, but was significantly affected by hyperbilirubinemia.     

Local treatment of pancreatic cancer metastases: A multicenter French study of the AGEO group

ObjectiveThis study reports the efficacy and safety of local treatment of metastases of pancreatic ductal adenocarcinoma (PDAC), with a curative intent.MethodsWe retrospectively included patients with histologically proven PDAC, who underwent a local treatment for metastases between January 1, 2000 and December 31, 2017, from 11 French hospitals. Complications of local treatment were reported. Univariate Cox models were performed to identify prognosis factors associated with overall survival (OS) and disease-free survival (DFS).ResultsWe included 52 patients treated for 68 metastases; 33 (64%) of whom had metachronous metastases. Metastatic sites treated were: 39 (57%) hepatic, 18 (27%) pulmonary and 11 (16%) others. Metastases treatments were: 45 (66%) surgery, 9 (13%) radiofrequency and 14 (21%) other procedures. The rates of severe complications and mortality were respectively 10% and 4%. The median OS and DFS after local treatment were 36.5 months and 12.7 months, respectively. Prognosis factors associated with a shorter OS were: liver metastases when compared with lung metastases (HR 4.04; 95%CI: 1.18?13.81), N2 status of primary pancreatic tumor when compared to N0–N1 (HR 9.43; 95%CI: 2.44?36.36) and synchronous metastases when compared to metachronous metastases (HR 2.34; 95%CI: 1.05?5.23). N2 status of primary pancreatic tumor was associated with a shorter DFS when compared to N0-N1 (HR 2.82; 95%CI: 1.05–7.58).ConclusionIn this series of highly selected patients, local treatment of metastases from PDAC is associated with prolonged survival. The rate of severe complications was low. Factors associated with shorter OS were liver metastases, N2 status and synchronous metastases.     

Is early-stage pancreatic adenocarcinoma truly early: stage migration on final pathology with surgery-first versus neoadjuvant therapy sequencing

BackgroundNeoadjuvant therapy (NT) remains controversial in early-stage pancreatic ductal adenocarcinoma (PDAC), defined as clinical (c)Stage I-II. Our aim was to analyze rates of pathologic upstaging/downstaging for resectable PDAC treated with surgery-first (SF) vs. NT.MethodsUtilizing the National Cancer Data Base (NCDB), patients with cStage I-II PDAC who underwent pancreatoduodenectomy in 2006–2013 were pathologically staged using the AJCC 8th edition and compared by treatment sequencing.ResultsAmong 13,871 patients, 15.3% received NT. Despite higher pre-treatment T-stage (cT2: 71.9% vs. 56.3%, p < 0.001), NT patients had lower rates of pathologic nodal metastases (46.2% vs. 69.2% in SF, p < 0.001), suggesting higher rates of pathologic downstaging. In cStage II, 33.0% were upstaged to stage III after SF, vs. only 14.0% after NT. In cStage I, 65.5% were upstaged following SF, vs. 46.7% after NT (all p < 0.001). Patients with NT (HR-0.77, p < 0.001) or downstaging (HR-0.80, p < 0.001) had improved overall survival (OS).ConclusionNT is associated with reduction in unexpected upstaging, reduction in nodal positivity, and improved OS, compared to SF approach in putatively early-stage PDAC. Because clinical staging underestimates the underlying disease burden in resectable PDAC, patients with cStage I-II should be considered for NT.