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.     

Impact of spatio-temporal recurrence pattern on overall survival for invasive intraductal papillary mucinous neoplasia – A comparison with pancreatic ductal adenocarcinoma

BackgroundResections for intraductal papillary mucinous neoplasia (IPMN) have increased dramatically during the last decade. Recurrence pattern and impact of adjuvant chemotherapy for solid pancreatic ductal adenocarcinoma (PDAC) is well known, but not for invasive IPMN (inv-IPMN).ObjectivesTo elucidate the impact of spatio-temporal recurrence pattern and adjuvant chemotherapy on overall survival for inv-IPMN compared with PDAC.MethodsWe conducted a retrospective single-center observational study of consecutive patients ≥18 years of age who underwent resection for inv-IPMN or PDAC at Karolinska University Hospital, between 2009 and 2018. Different initial recurrence sites and time frames as well as predictors for death were assessed with multivariable Cox and logistic regressions. Survival analyses were performed using the Kaplan-Meier model and log rank test.ResultsOf 396 resected patients, 92 were inv-IPMN and 304 PDAC. Both recurrence rate and death rate within three-years were lower for inv-IPMN compared to PDAC (p = 0.006 and p = 0.007 respectively). Across the whole cohort, the most common recurrence patterns were multi-site (25%), single-site liver (21%) and single-site locoregional (10%) recurrence. The most prominent predictors for death in multivariable Cox regression, especially if occurred within the first year, were multi-site (HR 17.0), single-site peritoneal (HR 13.6) and single-site liver (HR 13.1) recurrence. These predictors were less common in inv-IPMN compared to PDAC (p = 0.007). The effect of adjuvant chemotherapy was similar in the two groups.ConclusionResected inv-IPMN exhibits a less aggressive recurrence pattern than PDAC that translates into a more favorable overall survival.     

Risk factors for short recurrence-free survival after resection of pancreatic neuroendocrine tumor (PanNET) liver metastases: which patients should undergo resection?

Abstract

Background: In the treatment of metastatic pancreatic neuroendocrine tumors (PanNETs), surgical resection is the first choice if curative resection is expected. However, most patients develop recurrence after resection of liver metastasis. Because one of the benefits of resection is to gain a tumor-free period for the patients, it is important to identify which patients achieve longer recurrence-free survival (RFS) by resection. In this study, the clinicopathological factors associated with RFS after resection of metastatic PanNETs in the liver were evaluated to identify the patient group that is suitable for resection.

Methods: Consecutively diagnosed patients with PanNET liver metastasis with resection at our hospital from January 2000 to July 2019 were evaluated. A total of 26 metastatic PanNET patients with primary liver resections were evaluated. The median follow-up time was 48.3?months.

Results: There were 18 NET recurrences of the total 26 resections, with a median RFS of 17.9?months. Independent risk factors for short RFS were a high Ki67 index (p?=?.009) and the number of resected tumors (p?=?.045). When the cut-off value for the Ki67 index was 5.0% and that for the number of resected tumors was 6, Ki67?>?5.0% tumors had shorter RFS (4.9?months vs. 38.2?months p?=?.006), and patients with tumors >?= 7 tumors had shorter RFS (4.7?months vs. 27.5?months p?=?.001).

Conclusions: These findings indicate that good candidates for resection of metastatic tumors of PanNETs could be patients with low Ki67 tumors and a small number of metastatic tumors.     

Preoperative predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma

BackgroundThis study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy.MethodsIncluded were patients who underwent PDAC resection (2014–2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection.Results836 patients with a median follow-up of 37 (interquartile range [IQR] 30–48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3–6 months and 226 patients (27%) within 6–12 months. LogCA 19–9 (OR 1.25 [95% CI 1.10–1.41]; P < 0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01–0.68]; P = 0.02) were associated with recurrence <3 months. LogCA 19–9 (OR 1.23 [95% CI 1.10–1.38]; P < 0.001) and 0–90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60–5.37]; P < 0.001) were associated with recurrence within 3–6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09–2.16]; P = 0.02) and logCA 19–9 (OR 1.24 [95% CI 1.14–1.35]; P < 0.001) were related to recurrence within 6–12 months.ConclusionThis study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies.     

A novel online calculator to predict perioperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma: an international multicenter study

BackgroundTo develop an easy-to-use model to predict the probability of perioperative blood transfusion (PBT) in patients undergoing liver resection for hepatocellular carcinoma (HCC).Method878 patients from Eastern Hepatobiliary Surgery Hospital of Shanghai were enrolled in the training cohort, while 691 patients from Tongji Hospital of Wuhan and 364 patients from two hospitals from Europe and America served as the Eastern and Western external validation cohorts, respectively. Independent predictors of PBT were identified and used for the nomogram construction. The predictive performance of the model was assessed using the concordance index (C-index) and calibration plot, and externally validated using the two independent cohorts. This model was compared with four currently available prediction risk scores.ResultsEight preoperative variables were identified as independent predictors of PBT, which were incorporated into the new nomogram model, with a C-index of 0.833 and a well-fitted calibration plot. The nomogram performed well on the externally Eastern and Western validation cohorts (C-indexes: 0.786 and 0.777). The discriminatory ability of the nomogram was superior to the four currently available prediction scores (C-indexes: 0.833 vs. 0.671–0.770). The nomogram was programmed into an online calculator, which is available at http://www.asapcalculate.top/Cal3_en.html.ConclusionA nomogram model, using an easy-to-access website, can be used to calculate the PBT risk and identify which patients undergoing HCC resection are at high risks of PBT and can benefit most by using blood conservation techniques.     

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

BackgroundEarly singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features.MethodsWe retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models.ResultsOur RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort.ConclusionsCompared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients’ outcomes.     

Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study

BackgroundThe aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study.MethodsData were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index.ResultsCompared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069–1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032–1.736; p = 0.0277). High carbohydrate antigen 19–9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261–2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199–1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001).ConclusionsOur large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.     

Evaluation of the significance of adjuvant chemotherapy in patients with stage ⅠA pancreatic ductal adenocarcinoma

BackgroundAlthough adjuvant chemotherapy is considered a standard treatment for resected pancreatic ductal adenocarcinoma (PDAC), its utility in stage ⅠA patients is unclear. We aimed to investigate the recurrence rate, surgical outcome, prognostic factors, effectiveness of adjuvant chemotherapy, and determination of groups in whom adjuvant chemotherapy is effective in patients with stage ⅠA PDAC.MethodsWe retrospectively analyzed 73 patients who underwent pancreatectomy and were pathologically diagnosed with stage ⅠA PDAC between 2000 and 2018. We evaluated the relation between clinicopathological factors, recurrence rates, and outcomes such as the recurrence-free and disease-specific survival rates (RFS and DSS, respectively).ResultsThe 5-year RFS and DSS rates were 52% and 58%, respectively. In multivariate analysis, a platelet-to-lymphocyte ratio (PLR) ≥ 170, prognostic nutrition index (PNI) < 47.5, and pathological grade 2 or 3 constituted risk factors for a shorter DSS (hazard ratios: 4.7, 4.6, and 4.1, respectively). Patients with 0–1 of these risk factors (low-risk group; n = 47) had significantly higher 5-year DSS rates than those with 2–3 risk factors (high-risk group; n = 26) (80% vs. 23%; P < 0.001). Patients in the low-risk group showed similar 5-year RFS rates regardless of whether they received or not adjuvant chemotherapy (75% vs 70%, respectively; P = 0.49). Contrarily, high-risk patients who underwent adjuvant chemotherapy had higher 5-year RFS rates than those who did not receive adjuvant chemotherapy (32% vs 0%; P = 0.045).ConclusionsIn stage IA PDAC, adjuvant chemotherapy seems to be effective only in a subgroup of high-risk patients.     

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.     

Conditional survival in pancreatic cancer: better than expected

BackgroundTraditional survival estimates after resection for pancreatic cancer are based on clinicopathological variables at the time of diagnosis. Estimates have not reflected time survived after resection, as investigated for other malignancies. The aim of the present study was to understand how survival estimates change after pancreatic resection for cancer based on time already survived (conditional survival).MethodsPancreatectomies performed for pancreatic ductal adenocarcinoma (PDAC) between 2001 and 2010 were reviewed. Clinicopathological variables were evaluated to identify predictors of survival. Expected survival according to a validated nomogram for pancreatic cancer as well as conditional survival estimates and actual survival were calculated.ResultsIn all, 186 patients underwent pancreatic resection for PDAC [154 (82.8%) Whipple, 26 (14.0%) distal and 6 (3.2%) total]. Median (range) survival was 22 (3.4–107.3) months. Predictors of overall survival were: absence of nodal disease [odds ratio (OR) 8.8], age <67 years (OR 8.4) and lower stage (OR 4.3). Expected survival according to the nomogram was 70% (1 year), 39.5% (2 years) and 24% (3 years). As time passed, and overall and expected survival decreased, conditional survival increased.DiscussionThe available prognostic system for PDAC underestimated survival compared with actual survival in the present study. Conditional survival estimates, based on accrued lifespan, were better than either predicted or actual survival, suggesting that survival is a dynamic, rather than static, concept. Conditional survival may, therefore, be a useful tool to allow patients and clinicians to project subsequent survival based on time accrued since resection.     

When to Perform Surgical Resection or Radiofrequency Ablation for Early Hepatocellular Carcinoma?: A Nomogram-guided Treatment Strategy

Radiofrequency ablation (RFA) is indicated for early-stage hepatocellular carcinoma (HCC), but the comparative efficacy between RFA and surgical resection (SR) is inconclusive. We aim to develop a prognostic nomogram for predicting recurrence-free survival (RFS) after RFA. We also evaluate the possibility of using nomogram in improving treatment algorithm.We retrospectively enrolled 836 patients with Barcelona Clínic Liver Cancer very-early/early-stage HCC receiving SR or RFA. A visually-orientated nomogram was constructed with Cox proportional hazards model, and number and size of tumor, platelet count, albumin level, and model for end-stage liver disease score were included. The concordance index of the nomogram was 0.69.Radiofrequency ablation patients were stratified into low and high-risk groups by the median of nomogram scores. The RFS and overall survival (OS) of 2 risk groups were compared with SR patients with propensity score matching analysis. SR provided better RFS and OS compared with high-risk (nomogram score ≥9.8) RFA patients in the propensity model. The 5-year RFS rates were 36% versus 11%, whereas the 5-year OS rates were 74% versus 60% for SR and high-risk RFA groups, respectively (both P < 0.05). However, SR was associated with better RFS (5-year RFS rates 41% vs 29%), but similar OS (5-year OS rates 80% vs 81%), compared with low-risk (nomogram score <9.8) RFA patients in the propensity model (P < 0.05 and P > 0.05, respectively).In conclusion, this user-friendly nomogram offers individualized recurrence risk estimation and stratification for early HCC patients receiving curative RFA. The nomogram can be integrated into current treatment algorithm. SR should be considered the first-line treatment for high-risk patients to achieve better long-term survival.     

Discrete Left Ventricle Outflow Tract Obstruction in Children: Incidence and Predictors of Recurrence. A Multi-Center Study

ObjectivesThe purpose of this study is to measure the incidence of recurrence of discrete subaortic stenosis (DSS) after primary resection in two major cardiac centers in Saudi Arabia and to identify risk factors associated with recurrence.MethodsData on 234 patients who were diagnosed with DSS and underwent surgical resection between 1999 and 2018 were retrospectively reviewed. Patient demographics as well as echocardiographic, surgical, and pathological data were compared between patients with recurrence and non-recurrence.ResultsThe overall recurrence incidence after primary resection was 44.87% (N = 105). Most patients were male (59%). The median age at the 1^st operation was 60 months (range 3 months to 133 months). The presence of aortic stenosis at the time of diagnosis was significantly associated with recurrence (p-value = 0.002). The overall median peak gradient in which the primary resection was indicated is 60 mmHg (range 11 to 152 mmHg). The median peak gradient pre-operation and post-operation were significantly higher for the recurrence group (p-value=0.018 and p<0.001, respectively). We used univariate and multivariate analysis and controlled for the follow-up time, but there were no significant independent predictors of recurrence.ConclusionThe recurrence rate of DSS after the primary resection is relatively high in this study. Further prospective studies are needed to draw a definite conclusion on risk factors for recurrence after primary resection.     

Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy

Purpose

Loco (regional)-recurrence rate after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) remains high, and the efficiency of adjuvant chemoradiotherapy is still debated. We aimed to assess predictors of loco-recurrence in order to tailor the indications for adjuvant chemoradiotherapy.

Methods

Patients who underwent PD for PDAC between January 2001 and December 2010 were retrieved from a prospective database. Tumor recurrence was categorized as either loco-recurrence or distant recurrence. Clinicopathological characteristics and survivals were compared between patients with different recurrence patterns. The predictors for loco-recurrence were assessed.

Results

Seventy-nine patients were included. Loco-recurrence alone was identified in 22 patients (27.8%), distant recurrence alone in 33 (41.8%), both loco- and distant recurrences in 17 (21.5%) and no recurrence in 7 (8.9%). Median survival after recurrence (SAR) was significantly better in patients with loco-recurrence alone than in those with distant recurrence alone (10.4 vs. 5.0?months, P?=?0.002) or in those with both loco- and distant recurrences (10.4 vs. 5.8?months, P?=?0.044); the survival for patients with distant recurrence alone and those with both patterns was identical. Patients with early recurrence had a significantly poorer SAR than those with late recurrence (median, 5.5 vs. 9.0?months, P?=?0.001). Logistic regression analysis revealed that positive resection margin (P?=?0.001, HR?=?14.532; 95% CI 7.399–38.466), early T stage (P?=?0.018, HR?=?0.014; 95% CI 0.000–0.475) and large tumor size (P?=?0.030, HR?=?4.345; 95% CI 1.152–16.391) were the determinant factors directly related to loco-recurrence alone.

Conclusions

Patients with PDAC loco-recurrence alone had a significantly better SAR than those with distant recurrence. Adjuvant chemoradiotherapy should be considered to reduce loco-recurrence further and improve long-term survival.     

Evaluation of Gold’s nomogram for predicting recurrence-free survival in gastrointestinal stromal tumors in Indian patients

Gold described a nomogram for prediction of recurrence-free survival (RFS) after surgery for gastrointestinal stromal tumors (GIST). This retrospective study was intended to evaluate the utility of this nomogram for predicting a 2-year RFS in our patients. Twenty-eight consecutive eligible patients from January 2009 to January 2013 who underwent R0 resection and had histopathologically proven GIST were included in the study. Nomogram predicted RFS was compared with observed RFS in four groups as in the National Institutes of Health (NIH)-Fletcher classification. Calibration was assessed by plotting the predicted probabilities of RFS against the actual outcome. For validation of the nomogram, the graph obtained should be closer to the 45-degree line. The observed overall 2-year RFS was 85.7 % (24 patients). Four patients had recurrence within 2 years. The observed RFS was 87.5 %, 77.8 %, 90 %, and 100 % in the high, intermediate, low, and very low risk groups, respectively. The nomogram predicted the 2-year RFS was 40 %, 84.8 %, 88.6 %, and 90 % for high, intermediate, low, and very low risk groups, respectively. Thus, the predicted probabilities of the 2-year RFS in intermediate, low, and very low risk groups were similar to the observed outcomes. However, for the high risk group, the observed RFS was better than predicted RFS. This variation in the high risk group may be due to the use of adjuvant imatinib in our study.     

Clinical significance of serum carbohydrate antigen 19.9 and duke pancreatic monoclonal antigen type 2 for the prediction of hematogenous metastases in patients with pancreatic ducal adenocarcinoma

ObjectivesThe aim of the present study was to investigate the effectiveness of serum carbohydrate antigen (CA) 19.9 and duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in the prediction of early hematogenous metastases and as indicators of neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf the 293 enrolled PDAC patients, 61 had hematogenous metastases at the initial evaluation. One hundred and twenty patients without metastases underwent surgical resection. Of the 120 patients who underwent surgical resection, 45 underwent preoperative treatment and 29 developed early hematogenous metastases within 1 year after the surgery. In patients who underwent preoperative therapy, serum CA 19.9 and DUPAN-2 levels were measured within 2 weeks before the preoperative therapy and the subsequent surgery.ResultsThe elevated serum CA 19.9 and DUPAN-2 levels were significantly associated with hematogenous metastasis at initial evaluation and early hematogenous metastasis after surgery. The rate of early hematogenous metastasis and overall survival (OS) in patients with high CA 19.9 and/or high DUPAN-2 (CA 19.9 > 200 U/mL and/or DUPAN-2 >300 U/mL) were 46.3% and 18 months, respectively, whereas the metastatic rate and OS in patients with low CA 19.9 and DUPAN-2 were 12.7% and 37.5 months, respectively. Furthermore, in patients with high CA 19.9 and/or high DUPAN-2, preoperative therapy significantly reduced the rate of early hematogenous metastasis and prolonged the OS.ConclusionsSerum CA 19.9 and DUPAN-2 levels are useful predictors of early hematogenous metastasis and indicators for effectiveness of neoadjuvant therapy in PDAC patients.     

Isolated pulmonary recurrence after resection of pancreatic cancer: the effect of patient factors and treatment modalities on survival

BackgroundThe literature suggests favorable survival for patients with isolated pulmonary recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) as compared to other recurrence patterns. Within this cohort, it remains unclear what factors are associated with improved survival.MethodsPatients who developed pulmonary recurrence after pancreatectomy were selected from a prospective database. Predictors for post-recurrence survival (PRS) were analyzed using a multivariable Cox regression model.ResultsNinety-six patients were included. Median recurrence-free survival (RFS), PRS and overall survival (OS) were 16.3, 18.8 and 39.6 months, respectively. Further systemic treatment and/or metastasectomy (n = 64, 67%) was associated with significantly improved PRS and OS when compared to best supportive care (n = 35, 22%) (26.3 vs. 5.3 and 48.1 vs. 18.4, respectively; both P < 0.001). Patients who were able to undergo metastasectomy (n = 19) achieved a PRS and OS of 35.0 and 68.9 months, respectively. More than 5 pulmonary lesions, symptoms and CA 19-9 ≥100 U/mL at time of recurrence were predictive of decreased PRS. A recurrence-free interval of >16 months and treatment for recurrence were independently associated with improved PRS.ConclusionsIsolated pulmonary recurrence occurs in 13% of patients with recurrent PDAC and is associated with a median OS of 40 months. Aggressive treatment in highly selected patients was correlated with improved survival.     

Development and multicenter validation of a nomogram for preoperative prediction of lymph node positivity in pancreatic cancer(NeoPangram)

Background: Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer. This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease. Methods: A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts. Multivariate logistic regression analysis was used to construct the nomogram. Model performance was evaluated by discrimination, calibration, and clinical usefulness. An independent multicenter cohort consisting of 250 patients was used for external validation. Results: A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9), CA125, CA50, and CA242. A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis: risk score of the four-marker signature, computed tomography-reported LN status, and clinical tumor stage. The prediction model exhibited good discrimination ability, with C-indexes of 0.806, 0.742 and 0.763 for the development, internal validation, and external validation cohorts, respectively. The model also showed good calibration and clinical usefulness. A cut-off value(0.72) for the probability of LN metastasis was determined to separate low-risk and high-risk patients. Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status. Conclusions: This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.     

Nomogram for predicting the overall survival of the patients with oesophageal signet ring cell carcinoma

BackgroundThe purpose of this study was to explore the prognostic factors of oesophageal signet ring cell (SRC) carcinoma and to construct a nomogram for predicting the outcome of SRC carcinoma of oesophagus.MethodsA total of 968 cases of oesophageal SRC carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Cases were divided into training cohort and validation cohort. Univariate and multivariable Cox analyses was performed to select the predictors of overall survival (OS for the nomogram. The performance of nomogram was validated with Harrell’s concordance index (C-index), calibration curves and decision curve analysis (DCA).ResultsThe 1- and 5-year OS in the training cohort were 0.446 and 0.146, respectively, and the 1- and 5-year OS in the validation cohort were 0.459 and 0.138. The independent prognostic factors for establishing the nomogram were marital status, invasion of the surrounding tissue, lymph node metastasis, distant metastasis, surgery and chemotherapy. The Harrell’s c-index value of the training cohort and validation cohort were 0.723 and 0.708. In the calibration curves, the predicted survival probability and the actual survival probability have a considerable consistency. DCA indicated the favourable potential clinical utility of the nomogram.ConclusionsA nomogram to predict the OS of patients with oesophageal SRC carcinoma was established. The validation of the nomogram fully demonstrates its great performance.     

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.