Recent advances in understanding the genetics of pancreatic ductal adenocarcinoma (PDAC) have led to the potential for a personalized approach. Several studies have described the feasibility of generating genetic profiles of PDAC with next-generation sequencing (NGS) of samples obtained through endoscopic ultrasound-guided tissue acquisition (EUS-TA). The aim of this study was to find the best EUS-TA approach for successful NGS of PDAC. We attempted to perform NGS with tissues from 190 patients with histologically proven PDAC by endoscopic ultrasound-guided fine-needle aspiration and endoscopic ultrasound-guided fine-needle biopsy at Samsung Medical Center between November 2011 and February 2015. The medical records of these patients were retrospectively reviewed for parameters including tumor factors (size, location, and T stage), EUS-TA factors (needle gauge [G], needle type, and number of needle passes) and histologic factors (cellularity and blood contamination). The sample used for NGS was part of the EUS-TA specimen that underwent cytological and histological analysis. NGS could be successfully performed in 109 patients (57.4%). In the univariate analysis, a large needle G (p=0.003) and tumor located in the body/tail (p=0.005) were associated with successful NGS. The multivariate logistic regression analysis revealed that the needle G was an independent factor of successful NGS (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; p=0.031). The needle G is an independent factor associated with successful NGS. This finding may suggest that the quantity of cells obtained from EUS-TA specimens is important for successful NGS.
Targeted deep sequencing across broad genomic regions has been used to detect circulating tumor DNA (ctDNA) in pancreatic ductal adenocarcinoma (PDAC) patients. However, since most PDACs harbor a mutation in KRAS, sequencing of broad regions needs to be systemically compared to analyzing only KRAS mutations for PDAC. Using capture-based targeted deep sequencing, we detected somatic tumor mutations in 17 fine needle aspiration biopsy and 69 longitudinal cell-free DNA (cfDNA) samples from 17 PDAC patients. KRAS mutations were detected in 10 out of 17 pretreatment patient plasma samples. Next, interrogation of genetic alterations in matched primary tumor samples detected ctDNA in 12 of 17 pretreatment plasma samples and cfDNA sequencing across the 83 target genes identified ctDNA in 15 of 17 cases (88.2% sensitivity). This improved sensitivity of ctDNA detection resulted in enhanced tumor burden monitoring when we analyzed longitudinal plasma samples. We found that cfDNA sequencing detected the lowest mutant allelic fractions and number of variants when complete response or partial response to chemotherapy was achieved. We demonstrated that ctDNA levels measured by targeted deep sequencing sensitively indicate the presence of cancer and correlate well with clinical responses to therapy and disease progression in PDAC patients.
We investigated the efficacy of prophylactic pancreatic stent placement for preventing postprocedure pancreatitis in patients undergoing endoscopic papillectomy. This retrospective study included 82 consecutive patients who underwent endoscopic papillectomy for benign ampullary neoplasm at Samsung Medical Center between August 2002 and June 2011. The patients were subdivided into two groups, namely, those who received prophylactic pancreatic stent placement and those who did not. Patient demographics, baseline blood test, tumor characteristics, and endoscopic treatment data were collected. The primary endpoint was postprocedure pancreatitis. There was no difference in the development of postprocedure pancreatitis between the stent group and the no stent group (6/54, 10.5% and 2/28, 7.14%, respectively; p=1.00). At baseline, there were no significant differences between the two groups in terms of their risk factors for pancreatitis except pancreatic duct dye injection. The stent group was more likely to have dye injection than the nonstent group (100% vs 42.8%, p<0.001). However, in a logistic regression analysis, no significant difference was observed in the risk factors for pancreatitis including dye injection. Our data suggest that routine prophylactic pancreatic duct stent placement in all patients undergoing endoscopic papillectomy may not be necessary and that large-scale prospective studies are required to identify the subgroup of patients who would benefit.
24 October 2017 in Scandinavian Journal of Gastroenterology
Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is effective for tissue diagnosis of pancreatic mass. To improve diagnostic yield and drawbacks, 22-gauge (G) core biopsy (FNB) needle has been developed. This study aims to compare 22G FNA and FNB needles for EUS-guided sampling of suspected pancreatic cancer. Methods: This is a randomized controlled crossover trial. A total of 60 patients with suspected unresectable pancreatic cancer referred for EUS-guided sampling were randomly assigned to two groups. Both groups had 22G FNA and FNB needles performed in a randomized order. The primary endpoint was the cytological, histological and overall diagnostic accuracy of pancreatic cancer. Results: FNA and FNB needles reported similar level of diagnostic accuracy (FNA needle 95% vs. FNB needle 93.3%; p = .564), and it was not statistically different. However, cytological cellularity was significantly higher in the FNB needles compared to FNA needles (odds ratio 2.75, 95% confidence interval (CI)). There were no procedure-related complications in both needles. Conclusions: The diagnostic accuracy of EUS-guided sampling for pancreatic cancer using 22G FNA is comparable to FNB needles. The cytological quality of specimen is better in the FNB needle.
Jun Young Kim, Sang-geul Lee, Danbee Kang, Dong Kyu Lee, Joo Kyung Park, Kyu Taek Lee, Jong Kyun Lee, and Kwang Hyuck Lee. Gut and Liver 2021;15:922-9. https://doi.org/10.5009/gnl20257