Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study.

Background/Aims: : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods: : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results: : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions: : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

Comprehensive immunoprofile analysis of prognostic markers in pancreaticobiliary tract cancers.

Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T-cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD-1, PD-L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD-L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD-1+ immune cells (p = 0.0002) and CD8+ T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3+ (p = 0.0343) and CD8+ (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8+ (p = 0.0148), FOXP3+ (p = 0.0208), PD-1+ (p = 0.0318) cells in PDAC, and FOXP3+ cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p < 0.0001), mass size (p = 0.0004), metastasis (p = 0.006), PD-L1 (p < 0.0001), PD-1 (p = 0.003) and CD8 (p = 0.0063) was significantly associated with OS in PDAC, and CD8 (p = 0.007) was statistically related to OS in BTC. In multivariate analysis, prognostic factors were operation after chemotherapy (p = 0.021) in PDAC and CD8 (p = 0.037) in BTC. Therefore, immunoprofile analysis of cells expressing CD8, FOXP3, PD-1, and PD-L1 might have prognostic values in patients with pancreaticobiliary tract cancers.

Postoperative Prognostic Predictors of Bile Duct Cancers: Clinical Analysis and Immunoassays of Tissue Microarrays.

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of E-cadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0-2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0-2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions: This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Video Capsule Endoscopy Optimal Timing in Overt Obscure Gastrointestinal Bleeding.

Video capsule endoscopy (VCE) has become the noninvasive diagnostic standard in the investigation of overt obscure gastrointestinal bleeding (OGIB), with a high positive and negative predictive value. However, the diagnostic yield of the VCE is thought to depend on when it was performed. We evaluate the optimal timing performing VCE relative to overt OGIB to improve the diagnostic yield. A total 271 patients had admitted and underwent VCE for overt OGIB between 2007 and 2016 in Samsung Medical Center, Seoul, Korea. To evaluate the diagnostic yield of VCE for overt OGIB with respect to timing of the intervention, diagnostic yield was analyzed according to the times after latest bleeding. The finding of VCE was classified into P0 or P1 (no potential for bleeding or uncertain hemorrhagic potential) and P2 (high potential for bleeding, such as active bleeding, typical angiodysplasia, large ulcerations or tumors). The P2 lesion was found in 106 patients and diagnostic yield of was 39.1% for overt OGIB. Diagnostic yield of VCE to detect P2 lesion was higher when it is performed closer to the time of latest bleeding (timing of VCE between the VCE and latest bleeding: <24 h, 43/63 (68.3%); 1 days, 16/43 (34.9%); 2 days, 18/52 (34.6%); 3 days, 13/43 (30.2%); 4 days, 7/28 (25.0%); 5-7 days, 6/24 (25.0%), and ≥8 days, 4/18 (22.2%); ptrend < 0.001). The interval between the VCE and latest bleeding were categorized into <24 h (n = 63), 1-2 days (n = 95), 3-7 days (n = 95) and ≥8 days (n = 18). Multivariable analyses showed the odds ratio for P2 lesion detection was 4.99 (95% confidence interval, 1.47-16.89) in <24 h group, compared with ≥8 days group (p < 0.010). The overall re-bleeding rate for those with P2 lesion was higher than for those with P0 or P1 lesion at the end of mean follow up of 2.5 years. The proportion of patients who underwent therapeutic intervention including surgery, endoscopic intervention and embolization was higher when VCE is performed closer to the time of latest bleeding (p = 0.010). Early deployment of VCE within 24 h of the latest GI bleeding results in a higher diagnostic yield for patients with overt OGIB and consequently resulted in a higher therapeutic intervention rate.

Clinical Clues of Pre-Symptomatic Pancreatic Ductal Adenocarcinoma Prior to Its Diagnosis: A Retrospective Review of CT Scans and Laboratory Tests.

Most pancreatic ductal adenocarcinoma cases are unresectable at the time of diagnosis. Only early diagnosis and curative resection can help prolong survival. We tried to find out useful clinical clues of pre-symptomatic area prior to pancreatic cancer diagnosis compared to normal controls. Of 4799 patients diagnosed with pancreatic cancer between 1995 and 2014 at the Samsung Medical Center, 51 were selected for study. They had no symptoms at diagnosis and underwent computed tomography 6 to 36 months prior to diagnosis for reasons other than cancer diagnosis. We selected 288 control subjects who underwent computed tomography during the same period. Data were retrospectively reviewed included various variables. Fasting blood sugar (171.8 ± 97.5 vs. 115.8 ± 34.8 units, p < 0.05), new onset diabetes mellitus within 3 years (12/51 (23.5%) vs. 17/181 (9.8%), p < 0.05), carbohydrate antigen 19-9 level (609.5 ± 2342.5 vs. 17.0 ± 26.2, p = 0.08), main pancreatic duct dilatation (26/51 (51.0%) vs. 57/181 (31.5%), p < 0.05) in computed tomography scan were higher in pancreatic cancer group than in normal group, respectively. In multi-variate analysis, carbohydrate antigen 19-9, new onset diabetes mellitus (<3 years), and segmental main pancreatic duct dilatation were independent risk factors for pancreatic cancer. Our study concluded that independent risk factors for pancreatic cancer were elevated carbohydrate antigen 19-9, new onset diabetes mellitus (<3 years), and local main pancreatic ductal dilatation on computed tomography scan.

Clinical significance of circulating tumor cells after chemotherapy in unresectable pancreatic ductal adenocarcinoma.

Circulating tumor cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). A total of 52 patients with PDAC were prospectively enrolled in this study. Peripheral blood samples were serially collected at the time of diagnosis and after chemotherapy with clinical assessments. CTCs were isolated through a centrifugal microfluidic disc, enumerated with immunostaining against Epithelial cell adhesion molecule (EpCAM), Cytokeratin (CK), Plectin-1 and CD45, and identified by an automated imaging system. One or more CTCs were detected in 84.62% patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumor sizes, location and metastatic sites. The absolute number of CTCs after chemotherapy was inversely related to overall survival (OS), and the decreased number of CTCs after chemotherapy was significantly associated with longer OS in patients with PDAC. Identifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survival in patients with unresectable PDACs.

Aspirin Use Is Not Associated with the Risk of Metachronous Gastric Cancer in Patients without Helicobacter pylori Infection.

INTRODUCTION: Helicobacter pylori (H. pylori) eradication can prevent metachronous gastric cancer (MGC) after the performance of an endoscopic resection for early gastric cancer (EGC). However, 50% of infections persist after eradication, and the identification of MGC protective factors is important. The anti-tumor activity of aspirin has been demonstrated, but its efficacy in preventing MGC remains controversial. We evaluated the effect of aspirin on metachronous recurrence in H. pylori-negative patients. METHODS: A total of 4351 patients were evaluated between January 2007 and December 2016, and 2151 patients who met the inclusion criteria were analyzed. The primary outcome was the cumulative incidence of MGC after an endoscopic resection for EGC. RESULTS: During a 5-year median follow-up (interquartile range, 3.5-6.2), MGC developed in 176 (7.7%) patients, with a cumulative incidence of 89.4% in aspirin users and 92.7% in non-users; this difference was not statistically significant (p = 0.64). The duration of aspirin uses and the occurrence of MGC in both groups were not significantly different. There was no significant difference between groups when the duration of aspirin use was categorized into ≤1 year (hazard ratio (HR), 0.64; 0.20-2.01, p = 0.45), 1-4 years (HR, 1.35; 0.66-2.76, p = 0.41), and >4 years (HR, 1.17; 0.67-2.03, p = 0.58). CONCLUSIONS: Aspirin use was not associated with a lower risk of MGC in H. pylori-negative patients. Further prospective studies are needed.