scholarly journals Integration of Global Metabolomics and Lipidomics Approaches Reveals the Molecular Mechanisms and the Potential Biomarkers for Post-Operative Recurrence in Early Stage Cholangiocarcinoma

Author(s):  
Sureerat Padthaisong ◽  
Jutarop Phetcharaburanin ◽  
Poramate Klanrit ◽  
Jia V. Li ◽  
Nisana Namwat ◽  
...  

Abstract Background: Cholangiocarcioma (CCA) is a major health problem for people in Thailand. The treatment is challenging because most of patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcome. Methods: We performed 1H-NMR and UPLC-MS based-metabolomics on CCA serum. The differential metabolites were further analyzed using pathway analysis and potential biomarkers identification.Results: At an early stage, CCA patients with recurrence have a different metabolic profile compared with non-recurrence patients. In recurrence patients, the metabolites involved in energy metabolism, such as pyruvate metabolism and the TCA cycle, are down-regulated, while most lipids, including TGs, PCs, PEs and Pas, are up-regulated. This metabolic feature has been described in cancer stem-like cell (CSC) metabolism. Based on this, the correlation of putative CSC markers and proteins involved in identified pathways, together with recurrence-free survival was explored. The results revealed that the expression levels of the CSC markers CD44v6 and CD44v8-10 are associated with CD36 (a protein involved in lipid uptake) as well as with recurrence-free survival. Potential metabolic biomarkers were identified using ROC and Kaplan-Meier analyses. We found that citrate, sarcosine, succinate, creatine, creatinine and pyruvate and TGs have good predictive values for CCA recurrence and are associated with recurrence-free survival. Conclusions: These findings reveal an alteration of the metabolic profile associated with recurrence. These metabolic changes may be associated with the existence of CSCs that lead to CCA recurrence. Moreover, the alteration of metabolites was shown to provide suitable biomarkers for CCA recurrence. Therefore, the differential metabolites between patients with and without recurrence can be used as biomarkers for CCA recurrence.

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sureerat Padthaisong ◽  
Jutarop Phetcharaburanin ◽  
Poramate Klanrit ◽  
Jia V. Li ◽  
Nisana Namwat ◽  
...  

Abstract Background Cholangiocarcioma (CCA) treatment is challenging because most of the patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcomes. Methods We performed 1H-NMR and UPLC-MS-based metabolomics on the CCA serum. The differential metabolites were further analyzed using pathway analysis and potential biomarker identification. Results At an early stage, the metabolites involved in energy metabolisms, such as pyruvate metabolism, and the TCA cycle, are downregulated, while most lipids, including TGs, PCs, PEs, and PAs, are upregulated in recurrence patients. This metabolic feature has been described in cancer stem-like cell (CSC) metabolism. In addition, the CSC markers CD44v6 and CD44v8-10 are associated with CD36 (a protein involved in lipid uptake) as well as with recurrence-free survival. We also found that citrate, sarcosine, succinate, creatine, creatinine and pyruvate, and TGs have good predictive values for CCA recurrence. Conclusion Our study demonstrates the possible molecular mechanisms underlying CCA recurrence, and these may associate with the existence of CSCs. The metabolic change involved in the recurrence pathway might be used to determine biomarkers for predicting CCA recurrence.


2021 ◽  
Vol 10 (5) ◽  
pp. 1058
Author(s):  
Grégoire Rocher ◽  
Thomas Gaillard ◽  
Catherine Uzan ◽  
Pierre Collinet ◽  
Pierre-Adrien Bolze ◽  
...  

To determine if the time-to-chemotherapy (TTC) after primary macroscopic complete cytoreductive surgery (CRS) influences recurrence-free survival (RFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC). We conducted an observational multicenter retrospective cohort analysis of women with EOC treated from September 2006 to November 2016 in nine institutions in France (FRANCOGYN research group) with maintained EOC databases. We included women with EOC (all FIGO stages) who underwent primary complete macroscopic CRS prior to platinum-based adjuvant chemotherapy. Two hundred thirty-three patients were included: 73 (31.3%) in the early-stage group (ESG) (FIGO I-II), and 160 (68.7%) in the advanced-stage group (ASG) (FIGO III-IV). Median TTC was 43 days (36–56). The median OS was 77.2 months (65.9–106.6). OS was lower in the ASG when TTC exceeded 8 weeks (70.5 vs. 59.3 months, p = 0.04). No impact on OS was found when TTC was below or above 6 weeks (78.5 and 66.8 months, respectively, p = 0.25). In the whole population, TTC had no impact on RFS or OS. None of the factors studied were associated with an increase in TTC. Chemotherapy should be initiated as soon as possible after CRS. A TTC greater than 8 weeks is associated with poorer OS in patients with advanced stage EOC.


2016 ◽  
Vol 101 (1-2) ◽  
pp. 7-13
Author(s):  
Ohseong Kwon ◽  
Seok-Soo Byun ◽  
Sung Kyu Hong ◽  
Ja Hyeon Ku ◽  
Cheol Kwak ◽  
...  

Partial nephrectomy has become a treatment of choice for clinical T1a renal masses. Some international guidelines suggest that partial nephrectomy can be applied also in clinical T1b tumors. The aim of this study was to evaluate the feasibility of partial nephrectomy for tumors larger than 4 cm. We reviewed the medical records of 1280 patients who underwent partial nephrectomy and had pathologically confirmed malignancy. Patients were categorized into two groups by the size of tumors on computed tomography image, with a cutoff value of 4 cm. The oncologic and functional outcomes were compared between the two groups. Recurrence-free survival after surgery was estimated using the Kaplan-Meier method. Of the 1280 patients, 203 patients (15.9%) had renal tumors larger than 4 cm. There were significantly more exophytic tumors (P < 0.001) and the R.E.N.A.L. scores were significantly higher (P < 0.001) in partial nephrectomy >4 cm. Mean ischemic times were significantly different (P < 0.001). After 24 months, mean creatinine level between partial nephrectomy >4 cm and partial nephrectomy ≤4 cm was not different significantly (P = 0.554). And the percent changes of glomerular filtration rate after partial nephrectomy were not different at last follow-up (P = 0.082). The 5-year recurrence-free survival rates were 96.6% in partial nephrectomy ≤4 cm, and 94.5% in partial nephrectomy >4 cm (P = 0.416). Based on the present findings, partial nephrectomy for tumors larger than 4 cm showed comparable feasibility and safety to partial nephrectomy for tumors ≤4 cm considering oncologic and functional outcomes, despite longer operative and ischemic time.


2020 ◽  
Vol 9 (10) ◽  
pp. 3306
Author(s):  
Wojciech Krajewski ◽  
Marco Moschini ◽  
Łukasz Nowak ◽  
Sławomir Poletajew ◽  
Andrzej Tukiendorf ◽  
...  

Background and Purpose: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2–6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits. Materials and Methods: Data from 645 patients with primary T1HG bladder cancer treated between 2001 and 2019 in 12 tertiary care centres were retrospectively reviewed. The study included patients who underwent reTURB before BCG induction (Pre-BCG group: 397 patients; 61.6%) and those who had reTURB performed after BCG induction (Post-BCG group: 248 patients, 38.4%). The decision to perform reTURB before or after BCG induction was according to the surgeon’s discretion, as well as a consideration of local proceedings and protocols. Due to variation in patients’ characteristics, both propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. Results: The five-year recurrence-free survival (RFS) was 64.7% and 69.1% for the Pre- and Post-BCG groups, respectively, and progression-free survival (PFS) was 82.7% and 83.3% for the Pre- and Post-BCG groups, respectively (both: p > 0.05). Similarly, neither RFS nor PFS differed significantly for a five-year period or in the whole time of observation after the PSM and IPW matching methods were used. Conclusions: Our results suggest that there might be no difference in recurrence-free survival and progression-free survival rates, regardless of whether patients have reTURB performed before or after BCG induction.


2020 ◽  
Vol 61 (4) ◽  
pp. 586-593
Author(s):  
Yanping Bei ◽  
Naoya Murakami ◽  
Yuko Nakayama ◽  
Kae Okuma ◽  
Tairo Kashihara ◽  
...  

ABSTRACT Surgery is the standard modality for early-stage I–II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80–94). The median follow-up period and OS was 39.8 months (range, 10–101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0–1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4104-4104
Author(s):  
Kiyoshi Hasegawa ◽  
Norihiro Kokudo ◽  
Masatoshi Makuuchi ◽  
Namiki Izumi ◽  
Takafumi Ichida ◽  
...  

4104 Background: Which is the best treatment for less advanced hepatocellular carcinoma (HCC) with good liver function remains one of the most important and unsolved problems. To solve this problem, we conducted this study and evaluated the therapeutic impacts of surgical resection (SUR), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) on long-term outcomes in patients with HCC. Methods: A large-scale database constructed by a Japanese nationwide survey was used for this study. Between 2000 and 2005, 28,510 patients with HCC were treated by SUR, PEI, or RFA, among whom we identify 12,968 patients with no more than 3 tumors (≤3cm) and liver damage of class A or B. The patients were divided into SUR group (n=5,361), RFA group (n=5,548), and PEI group (n=2,059). Rates of overall and recurrence-free survival were compared among them. Results: Median follow-up was 2.16 years. Overall survival rates at 3 and 5 years were respectively 85.3%/71.1% in the SUR group, 81.0%/61.1% in the RFA, and 78.9%/56.3% in the PEI. Recurrence-free survival rates at 3 and 5 years were 56.7%/36.2%, 42.8%/28.3%, and 35.7%/23.1%, respectively. On multivariate analysis, the hazard ratio for death was significantly lower in the SUR group than in the RFA (SUR vs. RFA:0.84, 95% confidence interval, 0.74-0.95; p=0.006) and the PEI (SUR vs. PEI:0.75, 0.64-0.86; p=0.0001). The hazard ratios for recurrence were also lower in the SUR group than in the RFA (SUR vs. RFA:0.74, 0.68-0.79; p=0.0001) and the PEI (SUR vs. PEI:0.59, 0.54-0.65; p=0.0001). Conclusions: Surgical resection would provide longer overall and recurrence-free survival than either RFA or PEI in patients with HCC.


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