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.

Comparison of EUS and ERCP-guided tissue sampling in suspected biliary stricture.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are commonly used diagnostic modalities in biliary strictures. We compared the diagnostic yield of EUS and ERCP-based tissue sampling in intrinsic biliary strictures without extrinsic mass outside the bile duct. METHODS: A total of 85 patients who underwent ERCP and EUS for diagnosis of suspected biliary strictures confined to the bile duct were analyzed retrospectively at Samsung Medical Center, Seoul, Korea, between 2010 and 2018. RESULTS: Seventy-one patients were diagnosed with malignancy and 14 patients were diagnosed with benign strictures. EUS-based tissue sampling was more sensitive and accurate than ERCP-based tissue sampling (p = 0.038). The overall sensitivity and accuracy were 67.6% (95% confidence interval (CI) 56.1-77.3) and 72.9% (95% CI 62.7-81.2) for ERCP-based sampling, and 80.3% (95% CI 69.6-87.9) and 83.5% (95% CI 74.2-89.9) for EUS-based sampling, respectively. EUS-based sampling was superior to ERCP-based sampling in distal bile duct strictures (accuracy: 87.0% vs. 72.5%, p = 0.007), but not in perihilar strictures. In cases without intraductal mass, EUS-based tissue sampling was also superior to ERCP-based sampling (accuracy: 83.3% vs. 69.7%, p = 0.029), but not in cases with mass. CONCLUSION: EUS-based tissue sampling was superior to ERCP-based method in intrinsic biliary stricture with no mass outside the bile duct, particularly in those without intraductal mass or those with strictures located in distal bile duct. Therefore, EUS-based sampling should be considered for making a pathological diagnosis of suspected distal bile duct strictures even in lesions without definite mass.

Recurrence pattern and surveillance strategy for rectal neuroendocrine tumors after endoscopic resection.

BACKGROUND AND AIM: Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. METHODS: We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3). RESULTS: A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38-2.23). Extracolonic metastasis was not detected in this study. CONCLUSION: Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non-metastatic rectal NETs. However, regular endoscopic follow-up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs.

Incidence of and Risk Factors for Alcohol Relapse After Liver Transplantation for Alcoholic Liver Disease: Comparison Between Deceased Donor and Living Donor Liver Transplantation.

BACKGROUND: There are controversies over whether patients with alcohol-related liver disease (ALD) should follow the "6-month abstinence rule" before undergoing liver transplantation (LT), especially in case of living donor LT (LDLT). We analyzed the risk of alcohol relapse among ALD patients who received LT according to donor types and abstinence period before LT. METHODS: A total of 129 patients (mean 50.7 ± 9.2 years, male 78.3%) who underwent LT between January 2000 and July 2017 for ALD at Samsung Medical Center, Seoul, Korea, were analyzed. Alcohol relapse was defined as any use of alcohol after LT. RESULTS: The alcohol relapse rate was lower in LDLT recipients compared with that in DDLT recipients (13.9% vs. 31.7% at 3 years, P = 0.013). DDLT recipient, short abstinence period (< 6 months), and current smoking status were factors associated with alcohol relapse. The alcohol relapse rate was highest (54.5% at 3 years) for current smokers without 6-month sobriety who received DDLT, and it was lowest for never/ex-smoker with 6-month sobriety who received LDLT (4.3% at 3 years). For LDLT recipients, the alcohol relapse rate was not different according to abstinence period (17.7% vs. 11.6% at 3 years for short abstinent period < 3 months vs. ≥ 3 months, P = 0.92), but it was higher for current smokers compared with that for non/ex-smokers (22.4% vs. 5.8% at 3 years, P = 0.05). CONCLUSION: When considering LDLT for ALD, sobriety period may not be an absolute contraindication as abstinence period showed a weak association with alcohol relapse. Smokers need careful attention for alcohol relapse.

Effects of Novel Probiotics in a Murine Model of Irritable Bowel Syndrome.

Background/Aims: Dysbiosis is an important factor in the pathogenesis of irritable bowel syndrome (IBS). Several studies have reported promising results using probiotics for the treatment of IBS. This study evaluated the efficacy of novel probiotics isolated from Kimchi, a Korean fermented food, and the feces of healthy Vietnamese people in a murine model of IBS. Methods: Lactobacillus paracasei DK121 was isolated from Kimchi, and L. salivarius V4 and L. plantarum V7 were isolated from the feces of healthy Vietnamese people residing in Korea. Forty rats were allocated to receive one of the study strains, a mixture of the strains, or the vehicle. After 5 days of administration, the rats were restrained in a cage to induce IBS. The effects of the probiotics on IBS were analyzed by evaluating the stool weights and stool consistency scores. Results: The primary outcome was analyzed upon the completion of a three-week experiment. The rats in the V7 group showed lower stool weights than those in the control group at week 2 (median: 1.10 [V7] vs. 2.35 [control], p=0.04, Mann-Whitney U-test) and week 3 (median: 1.10 [V7] vs. 2.80 [control], p=0.017). The rats in the DK121 (median: 2.00, p=0.007), V7 (median: 2.00, p=0.004), and mixture (median: 1.50, p=0.001) groups showed better stool consistency scores at week 2 than the control group (median: 3.00). Conclusions: The novel probiotics have beneficial effects on defecation in a murine model of IBS. Human studies confirming the efficacy are warranted.

In vitro effect of clinical propofol concentrations on platelet aggregation.

The inhibitory effect of propofol on platelet aggregation remains unclear, and studies on the subject disagree. Furthermore, although propofol infusions are widely used for general anesthesia and as sedatives for patients in intensive care units, little information is available on its concentration- and time-related effects on platelet aggregation. Here, the authors investigated the in vitro effect of propofol, at concentrations required for sedation and general anesthesia, on platelet aggregation after 1, 2, or 3 h. Blood from healthy volunteers (n = 9) was incubated at propofol plasma concentrations of 0, 2, 4, and 10 µg/mL in a water bath at 37°C. Platelet aggregation was measured using a platelet function analyzer (PFA-100) after 1, 2, or 3 h of incubation. Times to occlude collagen/epinephrine (CEPI) or collagen/adenosine 5'-diphosphate (CADP)-coated membranes (closure times, CTs) were measured. The CEPI and CADP CTs of non-incubated blood were 125.6 ± 19.5 s and 93.0 ± 12.2 s, respectively, and no significant difference in CEPI CTs was observed at propofol plasma concentrations of 0, 2, 4, and 10 µg/mL after incubation for 1, 2, or 3 h. CADP CTs were comparable at propofol concentrations of 0, 2, 4, and 10 µg/mL at each incubation time. These findings suggest that propofol at concentrations required for sedation and general anesthesia has no inhibitory effect on platelet aggregation after 3 h of incubation.

In vitro effect of clinical propofol concentrations on red blood cell aggregation and deformability.

This in vitro study investigated time-related effects of propofol at the plasma concentrations required for sedation and general anaesthesia, on RBC aggregation, deformability, and morphology. Blood containing propofol at plasma concentrations of 0, 2 and 4 µg ml-1 was incubated in a water bath at 37°C for 1, 2, or 4 hours. RBC elongation indices (EIs) and aggregation indices (AIs), which represent RBC deformability and aggregation, respectively, were measured. Also, RBC morphological indices (MIs), which represent RBC morphology, were calculated. EIs and AIs were similar at propofol concentrations of 0, 2, or 4 µg ml-1 after 1, 2, or 4 hours of incubation. MIs at propofol plasma concentrations 0 or 2 µg ml-1 were similar after 1, 2, and 4 hours of incubation, however, MI at a propofol concentration of 4 µg ml-1 after 4 hours of incubation was higher than its value after 1 or 2 hours of incubation. No significant difference was observed between MIs at propofol plasma concentrations 0, 2, or 4 µg ml-1 after 1, 2, and 4 hours of incubation. At clinical doses, propofol has no direct effects on RBC deformability, aggregation, or morphology over a 4 hours incubation period.