scholarly journals Developing a preoperative serum metabolome-based recurrence-predicting nomogram for patients with resected pancreatic ductal adenocarcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Seoung Yoon Rho ◽  
Sang-Guk Lee ◽  
Minsu Park ◽  
Jinae Lee ◽  
Sung Hwan Lee ◽  
...  

AbstractWe investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4131
Author(s):  
Alice Usai ◽  
Gregorio Di Franco ◽  
Margherita Piccardi ◽  
Perla Cateni ◽  
Luca Emanuele Pollina ◽  
...  

It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice.


2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Hongkai Zhuang ◽  
Zixuan Zhou ◽  
Zuyi Ma ◽  
Shanzhou Huang ◽  
Yuanfeng Gong ◽  
...  

Background: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) of pancreatic head remains poor, even after potentially curative R0 resection. The aim of this study was to develop an accurate model to predict patients’ prognosis for PDAC of pancreatic head following pancreaticoduodenectomy. Methods: We retrospectively reviewed 112 patients with PDAC of pancreatic head after pancreaticoduodenectomy in Guangdong Provincial People’s Hospital between 2014 and 2018. Results: Five prognostic factors were identified using univariate Cox regression analysis, including age, histologic grade, American Joint Committee on Cancer (AJCC) Stage 8th, total bilirubin (TBIL), CA19-9. Using all subset analysis and multivariate Cox regression analysis, we developed a nomogram consisted of age, AJCC Stage 8th, perineural invasion, TBIL, and CA19-9, which had higher C-indexes for OS (0.73) and RFS (0.69) compared with AJCC Stage 8th alone (OS: 0.66; RFS: 0.67). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the nomogram for OS and RFS were significantly higher than other single parameter, which are AJCC Stage 8th, age, perineural invasion, TBIL, and CA19-9. Importantly, our nomogram displayed higher C-index for OS than previous reported models, indicating a better predictive value of our model. Conclusions: A simple and practical nomogram for patient prognosis in PDAC of pancreatic head following pancreaticoduodenectomy was established, which shows satisfactory predictive efficacy and deserves further evaluation in the future.


2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Chen ◽  
Cui-Cui Zhao ◽  
Fei-Ran Chen ◽  
Guo-Wei Feng ◽  
Fei Luo ◽  
...  

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.


2020 ◽  
Vol 21 (4) ◽  
pp. 127-130
Author(s):  
V. U. Rayn ◽  
◽  
A. A. Chernov ◽  
S. O. Zabotkin ◽  
◽  
...  

Aim. To access overall and event-free survival rates in patients after surgical treatment of localized and locally spread pancreatic head cancer. Materials and methods. A single center observational trial was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. Data were collected retrospectively from 2007 to 2019. Patients with resectable tumors were included into the study whose final histology showed pancreatic ductal adenocarcinoma and en-bloc resection. According to the technical facilities and actual clinical protocols all patients received surgical treatment only and were then monitored. Data on progression patterns and survival rates were collected and calculated using Kaplan-Meier survival analysis. Results. Median overall survival (OS) after R0 pancreaticoduodenectomy was 16,8 months (IQR 10,9-23,5). Median progression-free survival was 10,6 mo. (IQR 8,0-20,7). OS in jaundiced patients was 4,9 mo. shorter than in patients without jaundice at the diagnosis (р = 0,011). Patients with serum bilirubin level < 100 μmol/l lived on average 7.2 months longer (p = 0.014). Most frequent sites of primary progression were liver and peritoneum, lungs, bones, lymph nodes of the abdominal cavity / retroperitoneal space, less often metastases were found in the skin and soft tissues. In 21.4% of cases metastases were found in several organs simultaneously with most frequent combination of liver and peritoneum, liver and lungs, lungs and bones. The median survival after progression was 7.1 ± 4.8 months Conclusion. Pancreatic duct adenocarcinoma has a high potential for progression and has therefore poor prognosis. To improve long-term outcomes, it is advisable to apply additional therapeutic options perioperatively.


2019 ◽  
Vol 2 (1) ◽  
pp. 22-27
Author(s):  
Xiaodong Tian ◽  
Jisong Li ◽  
Hongqiao Gao ◽  
Yan Zhuang ◽  
Yongsu Ma ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1291
Author(s):  
Jaewoo Kwon ◽  
Yejong Park ◽  
Eunsung Jun ◽  
Woohyung Lee ◽  
Ki-Byung Song ◽  
...  

Radical antegrade modular pancreatosplenectomy (RAMPS) is considered an effective procedure for left-sided pancreatic ductal adenocarcinoma (PDAC). However, whether there are differences in perioperative outcomes, pathologies, or survival outcomes between anterior RAMPS (aRAMPS) and posterior RAMPS (pRAMPS) has not been reported previously. We retrospectively reviewed and compared the demographic, perioperative, histopathologic, and survival data of patients who underwent aRAMPS or pRAMPS for PDAC. We also compared these two groups among patients without periadrenal infiltration or adrenal invasion. A total of 112 aRAMPS patients and 224 pRAMPS patients were evaluated. Periadrenal infiltration, neoadjuvant treatment, and concurrent vessel resection were more prevalent in the pRAMPS group. After excluding patients with periadrenal infiltration, 106 aRAMPS patients were compared with 157 pRAMPS patients. There were no significant differences between the aRAMPS and pRAMPS groups in the pathologic tumor size, resection margin, proportion of tangential margin in the R1 resection, and number of harvested lymph nodes. The median overall survival and disease-free survival also did not differ significantly between the two groups. We cautiously suggest that pRAMPS will not necessarily provide more beneficial histopathologic outcomes and survival rates for left-sided PDAC cases without periadrenal infiltration. If periadrenal infiltration is not suspected, aRAMPS alone should be sufficiently effective.


2019 ◽  
Vol 5 (suppl) ◽  
pp. 85-85
Author(s):  
Zhuzeng Yin ◽  
Rong Liu

85 Background: Adjuvant chemotherapy with gemcitabine (GEM) is standard care for resected pancreatic ductal adenocarcinoma (PDAC). Nab-paclitaxel plus gemcitabine (AG) vs gemcitabine (GEM) have shown better survival and tumor response with in advanced or metastatic PDAC. We aimed to determine the efficacy and safety of AG compared with GEM for resected PDAC. Methods: We retrospectively reviewed resectable PDAC patients (pts) who received AG or GEM as adjuvant chemotherapy from January 2013 to December 2016 at the Chinese PLA General Hospital, Bei Jing, China. Pts received nab-paclitaxel (125mg/m2) followed by GEM (1,000 mg/m2) on days 1, 8 every 3 weeks or GEM (1,000 mg/m2) alone on days 1, 8 every 3 weeks for 6 cycles unless disease progression or there was unacceptable level of adverse events. Disease free survival (DFS), overall survival (OS) and toxicity were analyzed. Results: Among 70 pts received AG or GEM as adjuvant chemotherapy, 10 pts were excluded due to the serious complication or R2 resection. The analysis was based on 30 pts in each group undergone complete macroscopic (R0 or R1) resection. Median DFS was 15.8 months (95% CI 13.1-18.5) in AG group (6 pts not arrived) compared with 12.2 months in GEM group (95% CI 9.6-14.8, P = 0.039, 3 pts not arrived). Median OS was 28.3 months (95% CI 21.9-34.6) in AG group (11 pts not arrived) as compared with 20.6 months in GEM group (95% CI 11.2-29.9, P= 0.028, 7 pts not arrived). The 2 years survival rate was 63.3% versus 43.3% in AG group versus GEM group. The most common adverse events of grade 3 or higher were leukopenia (32.3% in AG group vs. 20.7% in GEM group, P= 0.387), neutropenia (45.2% vs.31%, P= 0.298), G-CSF use (41.9% vs. 24.1%, P= 0.177), sensory peripheral neuropathy (51.6% vs. 24.1%, P= 0.036) and fatigue (3.2% vs. 3.4%, P= 0.737). Conclusions: Our results provide the evidence that the adjuvant combination of nab-paclitaxel plus gemcitabine significantly improved DFS and OS of resected PDAC.


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