scholarly journals Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuki Sunagawa ◽  
Masamichi Hayashi ◽  
Suguru Yamada ◽  
Hiroshi Tanabe ◽  
Keisuke Kurimoto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Surgical Margin ◽  
Surgical Margins ◽  
Detection Sensitivity ◽  
Field Cancerization ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Marker Panel ◽  
Methylation Marker

Abstract Background Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. Methods We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017–2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. Results Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352–9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). Conclusion Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

Adjuvant therapy with gemcitabine and stereotactic body radiation therapy versus gemcitabine alone for resected stage II pancreatic cancer: A prospective, randomized, open label, single-center trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15765-e15765
Author(s):  
Tao Ma ◽  
Xueli Bai ◽  
Qichun Wei ◽  
Shunliang Gao ◽  
Bingfeng Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Stereotactic Body Radiation Therapy ◽  
Stage Ii ◽  
Recurrence Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Local Disease Control ◽  
Resected Stage

e15765 Background: Although adjuvant chemotherapy with gemcitabine has for years been the standard of care for resected pancreatic cancer, the role of adjuvant radiation is still debatable. We aimed to investigate the efficacy of gemcitabine combined with stereotactic body radiation therapy (SBRT) as adjuvant therapy for resected stage II pancreatic cancer. Methods: This single center randomized controlled trial was designed to enroll 512 patients with stage II pancreatic cancer that underwent curative-intended radical resection from a large-volume tertiary pancreatic center in China. Patients were randomly assigned to gemcitabine-alone adjuvant chemotherapy or adjuvant SBRT (25 Gray in 5 fractions) followed by gemcitabine chemotherapy. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included locoregional recurrence-free survival (LRFS), overall survival (OS), and incidence of adverse events. Interim analysis was planned at the time of 2.5-years’ enrollment. Results: 40 patients were randomly assigned to treatment between Sep 1, 2015, and Mar 31, 2018 (21 to the gemcitabine group and 19 to the gemcitabine plus SBRT group). Of these, one was excluded because of ineligibility and one did not receive any treatment. The median RFS was 12.4 (9.3-15.6) months in the gemcitabine group and 14.7 (9.2-20.1) months in the gemcitabine plus SBRT group ( P= 0.753), with median LRFS of 18.2 (14.6-21.7) months in the gemcitabine group and 13.1 (9.1-16.8) months in the gemcitabine plus SBRT group ( P= 0.333). The median OS was 21.7 (19.5-24.0) months in the gemcitabine group and 16.9 (12.8-20.9) in the gemcitabine plus SBRT group ( P= 0.066). Grade 3 or 4 neutropenia, thrombocytopenia, nausea or vomiting, and liver dysfunction were all comparable between the two groups. Evaluation of data from the first 40 enrolled patients indicated that the addition of adjuvant SBRT was not associated with either better local disease control or recurrence free survival. And because of failure to achieve the accrual target, the trial was terminated prematurely. Conclusions: Adjuvant SBRT neither provided a survival benefit nor improved local disease control in resected stage II pancreatic cancer. Clinical trial information: NCT02461836.

scholarly journals NDRG2 correlated with favorable recurrence-free survival inhibits metastasis of mouse breast cancer cells via attenuation of active TGF-β production

2012 ◽  
Vol 33 (10) ◽  
pp. 1882-1888 ◽  
Author(s):  
Sang-seok Oh ◽  
Donghyeok Kim ◽  
Dong-Hee Kim ◽  
Hong Hee Chang ◽  
Kyung-Cheol Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Mouse Breast Cancer

scholarly journals Locally recurrent chondrosarcoma of the pelvis and limbs can only be controlled by wide local excision

2019 ◽  
Vol 101-B (3) ◽  
pp. 266-271 ◽  
Author(s):  
M. K. Laitinen ◽  
M. C. Parry ◽  
L-R. Le Nail ◽  
C. H. Wigley ◽  
J. D. Stevenson ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Primary Tumour ◽  
Surgical Margin ◽  
Recurrence Free Survival ◽  
Disease Specific Survival ◽  
Univariable Analysis ◽  
Free Survival ◽  
Local Recurrence Free Survival ◽  
Disease Specific ◽  
Significant Factors

Aims The purpose of this study was to investigate the potential for achieving local and systemic control after local recurrence of a chondrosarcoma of bone Patients and Methods A total of 126 patients with local recurrence (LR) of chondrosarcoma (CS) of the pelvis or a limb bone were identified from a prospectively maintained database, between 1990 and 2015 at the Royal Orthopaedic Hospital, Birmingham, United Kingdom. There were 44 female patients (35%) and 82 male patients (65%) with a mean age at the time of LR of 56 years (13 to 96). The 126 patients represented 24.3% of the total number of patients with a primary CS (519) who had been treated during this period. Clinical data collected at the time of primary tumour and LR included the site (appendicular, extremity, or pelvis); primary and LR tumour size (in centimetres); type of operation at the time of primary or LR (limb-salvage or amputation); surgical margin achieved at resection of the primary tumour and the LR; grade of the primary tumour and the LR; gender; age; and oncological outcomes, including local recurrence-free survival and disease-specific survival. A minimum two years’ follow-up and complete histopathology records were available for all patients included in the study. Results For patients without metastases prior to or at the time of local recurrence, the disease-specific survival after local recurrence was 62.5% and 45.5% at one and five years, respectively. After univariable analysis, significant factors predicting disease-specific survival were grade (p < 0.001) and surgical margin (p = 0.044). After multivariable analysis, grade, increasing age at the time of diagnosis of local recurrence, and a greater time interval from primary surgery to local recurrence were significant factors for disease-specific survival. A secondary local recurrence was seen in 26% of patients. Wide margins were a good predictor of local recurrence-free survival for subsequent recurrences after univariable analysis when compared with intralesional margins (p = 0.002) but marginal margins did not reach statistical significance when compared with intralesional margins (p = 0.084) Conclusion In cases of local recurrence of a chondrosarcoma of bone, we have shown that if the tumour is non-metastatic at re-staging, an increase in disease-specific survival and in local recurrence-free survival is achievable, but only by resection of the local recurrence with a wide margin. Cite this article: Bone Joint J 2019;101-B:266–271.

scholarly journals Highly sensitive and portable mRNA detection platform for early cancer detection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongxia Li ◽  
Antony R. Warden ◽  
Wenqiong Su ◽  
Jie He ◽  
Xiao Zhi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Early Stage ◽  
Point Of Care ◽  
Cancer Biomarker ◽  
Detection Sensitivity ◽  
Detection Methods ◽  
Mrna Detection ◽  
Amplification Method ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs’ GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).

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