Survival prediction for patients with malignant biliary obstruction caused by pancreatic cancer undergoing biliary drainage: the COMBO-PaS model.

BACKGROUND: Patients with pancreatic cancer-caused biliary obstruction (PC-BO) have poor prognosis, but we lack of tools to predict survival for clinical decision-making. This study aims to establish a model for survival prediction among patients with PC-BO. METHODS: A total of 172 patients with PC-BO treated with percutaneous biliary drainage were randomly divided into a training group (n = 120) and a validation group (n = 52). The independent risk factors for overall survival were selected to develop a Cox model. The predictive performance of M stage, hepatic metastases, cancer antigen 199, and the Cox model was determined. Naples prognostic score (NPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for 1-month mortality risk were compared with the Cox model. RESULTS: The Cox model was developed based on total cholesterol, direct bilirubin, hepatic metastases, cancer antigen 199, stenosis type, and preprocedural infection (all P < 0.05), which named "COMBO-PaS." The COMBO-PaS model had the highest area under the curves (AUC) (0.801-0.933) comparing with other predictors (0.506-0.740) for 1-, 3-, and 6-month survival prediction. For 1-month mortality risk prediction, the COMBO-PaS model had the highest AUC of 0.829 comparing with NPS, PNI, and CONUT. CONCLUSION: The COMBO-PaS model was useful for survival prediction among patients with PC-BO.

Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization.

OBJECTIVES: Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS: A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS: Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS: ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS: • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.

Transcatheter arterial chemoembolization alone versus combined with microwave ablation for recurrent small hepatocellular carcinoma after resection: a retrospective comparative study.

PURPOSE: To compare the efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) versus TACE alone for the treatment of recurrent small hepatocellular carcinoma (sHCC) after resection. MATERIALS AND METHODS: From June 2015 to January 2020, a total of 45 patients with recurrent sHCC (size ≤ 3 cm) treated by TACE-MWA or TACE were included in this study. The radiological response at 1-, 3-, 6-month after initial treatment [modified Response Evaluation Criteria in Solid Tumors (mRECIST)], progression-free survival (PFS), overall survival (OS), and complications were evaluated. RESULTS: The TACE-MWA group showed better 1-, 3-, 6-month tumor response rates than TACE group. The corresponding 1-, 3-, and 5-year PFS rates were 76.5%, 70.6%, and 70.6% for the TACE-MWA group, and 56.1%, 15.0%, and 15.0% for the TACE group (P = 0.003). The 1-, 3-, and 5-year OS rates were 100.0%, 82.1%, and 61.5% for the TACE-MWA group, and 89.0%, 58.1%, and 50.8% for the TACE group (P = 0.389), respectively. Moreover, no major complications related to treatment were observed in either of the groups. Compared with the TACE group, the TACE-MWA group had a significantly lower number of re-TACE sessions (P = 0.003). CONCLUSIONS: Although TACE alone provides equivalent effectiveness for recurrent sHCC in terms of OS rates, TACE-MWA had better 1-, 3-, 6-month tumor response rates and may prolong tumor PFS time.

Prognostic nomogram for acute pancreatitis after percutaneous biliary stent insertion in patients with malignant obstruction.

OBJECTIVE: This study aimed to develop and validate a nomogram to predict the risk of pancreatitis after percutaneous transhepatic biliary stent insertion (PTBS) in patients with malignant biliary obstruction (MBO). MATERIALS AND METHODS: We enrolled 314 patients who underwent PTBS for MBO from March 2016 to July 2021 in this retrospective study. We used univariate analysis to identify potential risk factors, while a multivariate logistic regression model was employed to establish a nomogram for predicting the risk of pancreatitis. The discrimination and calibration of the nomogram were evaluated by estimating the area under the receiver operator characteristic curve (AUC) and by bootstrap resampling and visual inspection of the calibration curve. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: After the procedure, 41 (13.1%) patients developed pancreatitis. Based on multivariate logistic regression analysis, young age (OR = 2.57, 95% CI 1.16 to 5.69), stent insertion across the papilla (OR = 6.47, 95% CI 2.66 to 15.70), and visualization of the pancreatic duct (OR = 15.40, 95% CI 6.07 to 39.03) were associated with an elevated risk of pancreatitis. Importantly, the performance of the nomogram was satisfactory, with an identical AUC (0.807, 95% CI 0.730 to 0.883) and high-level agreement between predicted and observed probabilities as suggested in calibration curves. The DCA curve subsequently confirmed the clinical utility. CONCLUSION: A predictive nomogram for pancreatitis after PTBS in patients with MBO was successfully established in the present study.

Percutaneous stent placement for malignant hilar biliary obstruction: side-by-side versus stent-in-stent technique.

BACKGROUND: Currently, side-by-side (SBS) and stent-in-stent (SIS) are the two main techniques for stent deployment to treat hilar biliary obstructions. Previous studies comparing these two techniques are very limited, and thus, no consensus has been reached on which technique is better. The purpose of this study is to compare the clinical efficacy and safety of SBS and SIS deployment via a percutaneous approach for malignant hilar biliary obstruction. METHODS: From July 2012 to April 2019, 65 patients with malignant hilar biliary obstruction who underwent bilateral stenting using either the SBS or SIS techniques were included in this study. Among them, 27 patients underwent SIS stent insertion (SIS group), and the remaining 38 patients underwent SBS stent insertion (SBS group). Technical success, improvement of jaundice, complications, duration of stent patency, and overall survival were evaluated. RESULTS: Technical success was achieved in all patients in the two groups. The serum bilirubin level decreased more rapidly 1 week after the procedures in the SBS group than in the SIS group (P = 0.02). Although the total complication rate did not differ between the two groups, cholangitis was found to be more frequent in the SIS group (P = 0.04). The median stent patency was significantly longer in the SBS group (149 days) than in the SIS group (75 days; P = 0.02). The median overall survival did not significantly differ between the two groups (SBS vs. SIS, 155 days vs. 143 days; P > 0.05). CONCLUSIONS: Percutaneous transhepatic bilateral stenting using either the SBS or SIS technique is safe and effective in the management of malignant hilar biliary obstruction. However, SBS offers a quicker improvement of jaundice, a lower incidence of cholangitis after the procedure, and a longer stent patency period than SIS.

A case-control study on the risk factors for hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an endemic communicable disease in China, accounting for 90% of total reported cases worldwide. In this study, the authors want to investigate the risk factors for HFRS in recent years to provide the prevention and control advices. METHODS: A community-based, 1:2 matched case-control study was carried out to investigate the risk factors for HFRS. Cases were defined as laboratory-confirmed cases that tested positive for hantavirus-specific IgM antibodies. Two neighbourhood controls of each case were selected by sex, age and occupation. Standardized questionnaires were used to collect information and identify the risk factors for HFRS. RESULTS: Eighty-six matched pairs were investigated in the study. The median age of the cases was 55.0 years, 72.09% were male, and 73.26% were farmers. In the multivariate logistic regression analysis, cleaning spare room at home (OR = 3.310, 95%CI 1.335-8.210) was found to be risk factor for infection; storing food and crops properly (OR = 0.279 95%CI 0.097-0.804) provided protection from infection. CONCLUSION: Storing food and crops properly seemed to be protective factor, which was important for HFRS prevention and control. More attention should be paid to promote comprehensive health education and behaviour change among high-risk populations in the HFRS endemic area.

Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study.

BACKGROUND & AIMS: Previous prognostic scores for transarterial chemoembolization (TACE) were mainly derived from real-world settings, which are beyond guideline recommendations. A robust model for outcome prediction and risk stratification of recommended TACE candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: Between January 2010 and May 2016, 1,604 treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh A5-B7 and performance status 0 undergoing TACE were included from 24 tertiary centres. Patients were randomly divided into training (n = 807) and validation (n = 797) cohorts. A prognostic model was developed and subsequently validated. Predictive performance and discrimination were further evaluated and compared with other prognostic models. RESULTS: The final presentation of the model was "linear predictor = largest tumour diameter (cm) + tumour number", which consistently outperformed other currently available models in both training and validation datasets as well as in different subgroups. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were further selected as cut-off values, leading to the "six-and-twelve" score which could divide patients into 3 strata with the sum of tumour size and number ≤6, >6 but ≤12, and >12 presenting significantly different median survival of 49.1 (95% CI 43.7-59.4) months, 32.0 (95% CI 29.9-37.5) months, and 15.8 (95% CI 14.1-17.7) months, respectively. CONCLUSIONS: The six-and-twelve score may prove an easy-to-use tool to stratify recommended TACE candidates (Barcelona Clinic Liver Cancer stage-A/B) and predict individual survival with favourable performance and discrimination. Moreover, the score could stratify these patients in clinical practice as well as help design clinical trials with comparable criteria involving these patients. Further external validation of the score is required. LAY SUMMARY: There is currently no prognostic model specifically developed for recommended or ideal transarterial chemoembolization (TACE) candidates with hepatocellular carcinoma, despite these patients being frequently identified as the best target population in pivotal randomized controlled trials. The six-and-twelve score provides patient survival prediction, especially in ideal candidates of TACE, outperforming other currently available models in both training and validation sets, as well as different subgroups. With cut-off values of 6 and 12, the score can stratify ideal TACE candidates into 3 strata with significantly different outcomes and may shed light on risk stratification of these patients in clinical practice as well as in clinical trials.

Incidence and management of oesophageal ruptures following fluoroscopic balloon dilatation in children with benign strictures.

OBJECTIVES: The purpose of this study is to investigate the incidence and management of oesophageal ruptures following fluoroscopic balloon dilatation (FBD) in children with benign oesophageal strictures. METHODS: Sixty-two children with benign oesophageal strictures underwent FBDs. Oesophageal rupture was categorized as intramural (type 1), transmural (type 2), or transmural with free leakage (type 3). The possible risk factors for oesophageal ruptures were analyzed. RESULTS: One hundred and twenty-nine FBDs were performed in these patients. The oesophageal rupture rate was 17.1 % (22/129). The majority (21/22) of ruptures were type 1 and type 2, both were treated conservatively. Only one patient had a type 3 rupture and underwent oesophagoesophagostomy. The patient gender, age, and the length and cause of the stricture showed no significant effect on the rupture (P > 0.05). However, for the patients ≤2 years old, the initial balloon with a diameter ≥10 mm showed a higher oesophageal rupture rate than those <10 mm during the first session (P = 0.03). CONCLUSIONS: Although the oesophageal rupture rate in children was 17.1 %, the type 3 rupture rate was 0.8 %, which usually requires aggressive treatment. For children ≤2 years old, the initial balloon diameter should be <10 mm in the first session for decreasing the risk of oesophageal rupture. KEY POINTS: • The oesophageal rupture rate following balloon dilatation in children was 17.1 %. • The incidence of transmural rupture with free leakage is very low. • Only transmural rupture with free leakage needs aggressive treatment. • For children ≤2 years, the initial balloon diameter should be <10 mm.

Fluoroscopic removal of retrievable self-expandable metal stents in patients with malignant oesophageal strictures: Experience with a non-endoscopic removal system.

OBJECTIVES: To evaluate clinical outcomes of fluoroscopic removal of retrievable self-expandable metal stents (SEMSs) for malignant oesophageal strictures, to compare clinical outcomes of three different removal techniques, and to identify predictive factors of successful removal by the standard technique (primary technical success). METHODS: A total of 137 stents were removed from 128 patients with malignant oesophageal strictures. Primary overall technical success and removal-related complications were evaluated. Logistic regression models were constructed to identify predictive factors of primary technical success. RESULTS: Primary technical success rate was 78.8 % (108/137). Complications occurred in six (4.4 %) cases. Stent location in the upper oesophagus (P=0.004), stricture length over 8 cm (P=0.030), and proximal granulation tissue (P<0.001) were negative predictive factors of primary technical success. If granulation tissue was present at the proximal end, eversion technique was more frequently required (P=0.002). CONCLUSIONS: Fluoroscopic removal of retrievable SEMSs for malignant oesophageal strictures using three different removal techniques appeared to be safe and easy. The standard technique is safe and effective in the majority of patients. The presence of proximal granulation tissue, stent location in the upper oesophagus, and stricture length over 8 cm were negative predictive factors for primary technical success by standard extraction and may require a modified removal technique. KEY POINTS: • Fluoroscopic retrievable SEMS removal is safe and effective. • Standard removal technique by traction is effective in the majority of patients. • Three negative predictive factors of primary technical success were identified. • Caution should be exercised during the removal in those situations. • Eversion technique is effective in cases of proximal granulation tissue.

Fluoroscopic-guided stent placement in failed tentative endoscopic approaches to malignant gastroduodenal obstructions.

Background Fluoroscopic or endoscopic placement of metallic stents is used as a safe, non-surgical, palliative treatment option for malignant gastroduodenal obstructions. However, endoscopic stent placement is not always feasible, due to the tight or tortuous stricture of the obstructed area and insufficient visualization of the stomach due to remnant food material. Purpose To assess the technical feasibility and clinical outcomes of fluoroscopic-guided stent placement in malignant gastroduodenal obstructions following the technical failure of endoscopic stent placement. Material and Methods In all, 19 patients (14 men, 5 women; age range, 36-85 years) were referred due to technical failures of tentative endoscopic stent placement. Indications were failure to pass the guide wire through the obstruction (n = 13), failure to reach the stricture lesion due to short endoscope (n = 5), and acute angulation of the stricture lesion (n = 1). Data were retrospectively collected regarding the technical and clinical success of the fluoroscopy, the dysphagia score before and after stent placement, and major complications and their management. Results Fluoroscopic stent placement was technically successful in 15/19 patients (79%). Failures were due to complete obstruction (n = 3) and acute angulation of the stricture lesion (n = 1). Clinical success was achieved in all 15 patients with successful stent placement. The dysphagia score significantly improved after stent placement ( P < 0.001). Complications occurred in 4/15 patients (27%), including tumor overgrowth (n = 2), stent collapse (n = 1), and jaundice (n = 1). Conclusion Fluoroscopic stent placement in malignant gastroduodenal obstructions following a technical failure of endoscopic stent placement is technically feasible and has an acceptable clinical outcome.

Gastroduodenal stent placement versus surgical gastrojejunostomy for the palliation of gastric outlet obstructions in patients with unresectable gastric cancer: a propensity score-matched analysis.

OBJECTIVES: To compare the outcomes between stent placement and surgical gastrojejunostomy (GJ) for the palliation of gastric outlet obstruction (GOO) in patients with unresectable gastric cancer. METHODS: A retrospective study was performed in a single university hospital in 224 patients with GOO, and who were treated either by stent placement (n = 124) or surgical GJ (n = 100). The outcomes were assessed with reference to the following variables with the use of propensity-score matching: success rates; complications; dysphagia scores, albumin, and body mass index; survival; symptom-free duration; and hospitalization. RESULTS: We identified a well-balanced cohort of 74 pairs of patients, matched on the basis of propensity score. The dysphagia score 7 days after treatment was significantly better in the stent group (P < 0.001). Albumin level 1 month after treatment was significantly lower in the stent group (P < 0.001). Symptom-free duration and hospitalization were significantly longer in the surgery group (P = 0.002, P < 0.001, respectively). The recurrence rate was significantly higher in the stent group (P = 0.032). CONCLUSIONS: Stent placement can provide faster symptom relief and shorter hospitalization, while surgical GJ can provide longer symptom-free duration, less recurrent obstruction symptoms and better nutritional status. KEY POINTS: • The two methods are equally effective in palliating gastric outlet obstruction symptoms • The stent group showed rapid and efficient palliation of symptoms • Recurrent symptoms were more frequent in the stent group • Surgical gastrojejunostomy provides a longer symptom-free duration and better nutritional status.

C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1/2-mediated epithelial-mesenchymal transition.

C5a and its receptor, C5a receptor (C5aR), play critical roles in tumor progression. However, mechanisms of C5a-C5aR axis in hepatocellular carcinoma (HCC) cell invasiveness are not fully elucidated. In this study, we found that C5aR expression was highly expressed in HCC cell lines and tumor tissues, and associated with capsular invasion, tumor stage and some epithelial-mesenchymal transition (EMT)-related markers. Activation of C5aR by C5a promoted HCC cell invasion and migration, whereas depletion of C5aR expression significantly impaired C5a-stimulated invasion and migration. Furthermore, we found that C5aR induced EMT in HCC cells, through downregulation of E-cadherin and Claudin-1 expression, and upregulation of Snail expression. Finally, we demonstrated that C5aR stimulated activation of ERK1/2, and ERK1/2 pathway was involved in C5aR-mediated EMT, cell invasion and migration of HCC cells. Thus, our data suggest that C5aR stimulates cell invasion and migration via ERK1/2-mediated EMT in HCC cells, and implicate that blocking C5aR expression has therapeutic promise to inhibit HCC invasiveness.

Arterioportal shunts in patients with hepatocellular carcinoma treated using ethanol-soaked gelatin sponge: therapeutic effects and prognostic factors.

PURPOSE: To evaluate the efficacy and safety of transarterial embolization with ethanol-soaked gelatin sponge (ESG) for the treatment of arterioportal shunts (APSs) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 61 patients with unresectable HCC was included in this study, conducted from June 2008 to November 2011. These patients, who were treated with APSs, had received transarterial therapy. They underwent transarterial embolization of the shunt with ESG followed by transarterial chemoembolization if available. Changes in APSs, tumor response (per modified Response Evaluation Criteria in Solid Tumors), postembolization events, patient survival, and prognostic factors were analyzed. RESULTS: The median follow-up period was 13 months (range, 3-34 mo). The immediate APS improvement rate was 97% (59 of 61), and the APS improvement rate at first-time follow-up was 54% (33 of 61). Tumor response at 2 months after first embolization was as follows: complete response in two patients (3.3%), partial response in 24 patients (39.3%), stable disease in 24 patients (39.3%), and progressive disease in 11 patients (18.1%). Survival rates were 79% at 6 months, 50% at 1 year, and 12% at 2 years; the median survival time was 382 days. Maximal tumor size and APS improvement at first-time follow-up were demonstrated to be independent prognostic factors (P < .05). CONCLUSIONS: Transarterial embolization with ESG may be safe and effective for the treatment of APSs in patients with unresectable HCC. Small maximal tumor size (< 5 cm) and an improvement in APSs favored overall survival.

Full-thickness esophageal perforation after fluoroscopic balloon dilation: incidence and management in 820 adult patients.

OBJECTIVE: The purpose of this study is to investigate the incidence, management, and outcomes of esophageal perforation after fluoroscopic balloon dilation in 820 adult patients with esophageal diseases. MATERIALS AND METHODS: Between December 1990 and April 2014, a total of 820 adult patients (age range, 21-93 years) underwent 1869 fluoroscopic balloon dilation sessions (mean, 2.3 sessions/patient; range, 1-29 sessions/patient) for esophageal diseases. We retrospectively reviewed the prospectively collected medical records and images of these patients and collected the data of patients who developed esophageal perforations after fluoroscopic balloon dilation. RESULTS: During this period, 12 patients (six men and six women; mean age, 51 years; age range, 28-69 years) developed perforations. The perforation rate was 1.5% per patient and 0.6% per dilation. Among the first eight patients, four who were treated with surgery had perforations 2 cm or larger, and the other four who underwent fasting, parenteral alimentation, and treatment with antibiotics had perforations smaller than 2 cm. The last four patients underwent stent placement immediately after the diagnosis, regardless of the perforation's size. The median hospital stay was 11.5 days. CONCLUSION: Fluoroscopic balloon dilation of esophageal diseases is a safe procedure with a low perforation rate. A perforation size greater than 2 cm is considered large and requires aggressive treatment. Although the number of patients with esophageal perforation we treated is relatively small and further clinical trials are needed, temporary stent placement seems to be an initial choice in the management of esophageal perforations after fluoroscopic balloon dilation.

IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2-ERK1/2 Pathway.

BACKGROUND: As a pro-inflammatory cytokine, IL-33 has been demonstrated to play an important role in tumor progression. It is reported that IL-33 is highly expressed in the serum and tumor tissues of patients with gastric cancer. However, the function of IL-33 in gastric cancer remains elusive. We here tried to elucidate the effects of IL-33 on gastric cancer cell invasion and migration. METHODS: Invasion assay and migration assay were performed to assess the effects of IL-33 on gastric cancer cell invasion and migration. ST2 receptor was silenced by siRNA, and ERK1/2 pathway was inhibited by U0126. Protein levels of MMP-3 and IL-6 in cell supernatant were measured by ELISA. RESULTS: IL-33 promoted the invasion and migration of gastric cancer cells, in a dose-dependent manner. Knockdown of the IL-33 receptor ST2 attenuated the IL-33-mediated invasion and migration. Furthermore, via ST2 receptor, IL-33 induced the activation of ERK1/2 and increased the secretion of MMP-3 and IL-6. In addition, blockage of ERK1/2 pathway resulted in inhibition of invasion and migration induced by IL-33, and downregulation of MMP-3 and IL-6 production. CONCLUSIONS: IL-33 promotes gastric cancer cell invasion and migration by stimulating the secretion of MMP-3 and IL-6 via ST2-ERK1/2 pathway. Thus, IL-33 may be a useful marker for the diagnosis and treatment of gastric cancer.

TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.

Transarterial Chemoembolization Plus Tyrosinkinase Inhibitors and PD-1 Inhibitors for Spontaneously Ruptured Hepatocellular Carcinoma.

PURPOSE: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with tyrosinkinase inhibitors (TKI) and PD-1 inhibitors, versus TACE monotherapy for the treatment of ruptured hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study included 104 patients with ruptured HCC receiving either combination therapy or TACE monotherapy at two centers between June 2015 and June 2022. Propensity score matching (PSM) analysis was used at a 1:2 ratio to reduce bias between the two groups. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were the occurrence of adverse events (AEs, Common Terminology Criteria for AEs, version 5.0.) and the peritoneal metastasis rate. RESULTS: A total of 69 patients were enrolled after PSM, including 23 patients in the combination group and 46 patients in the monotherapy group. The combination group exhibited a significantly longer median OS (553 days, 95% confidence interval [CI] 222.6-883.9) compared to the monotherapy group (105 days, 95% CI 81.2-128.7; P < 0.001). Similarly, the combination group showed a better median PFS (356 days, 95% CI 299.5-412.4) compared to the monotherapy group (97 days, 95% CI 75.9-118.1; P < 0.001). Moreover, there was no significant difference in the peritoneal metastasis rate (combination group: 8.6% vs. monotherapy group: 26.1%, P = 0.119). Grade 3 AEs occurred at a rate of 21.7% and 13% in combination and monotherapy groups, respectively. No Grade 4/5 AEs were observed in either group. CONCLUSIONS: Our study demonstrated that the combination of TACE with TKI and PD-1 inhibitors significantly enhances OS and PFS compared to TACE monotherapy in ruptured HCC patients. Furthermore, this combined approach exhibited an acceptable safety profile.

Acute Pancreatitis After Percutaneous Metallic Stent Insertion for Malignant Biliary Obstruction: A Retrospective 2-Center Study.

BACKGROUND/AIMS: The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction. MATERIALS AND METHODS: From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis. RESULTS: On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened. CONCLUSION: Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.

Prognostic value of des-γ-carboxyprothrombin in patients with AFP-negative HCC treated with TACE.

In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease.