BACKGROUND:Intraluminal postpancreatoduodenectomy hemorrhage is an uncommon but potentially devastating complication, with clinically complex and multifactorial sources. Current evidence on optimal management, particularly the role of angiography, remains controversial. This study aimed to optimize the management strategies for intraluminal postpancreatoduodenectomy hemorrhage by analyzing data from a high-volume center. METHODS:This single-center, retrospective study studied consecutive patients who underwent pancreatoduodenectomy from July 2018 to June 2025. The clinical manifestations, management, and outcomes of intraluminal postpancreatoduodenectomy hemorrhage were analyzed. RESULTS:Among the 3,011 patients who underwent pancreatoduodenectomy, intraluminal postpancreatoduodenectomy hemorrhage was observed in 115 patients (3.8%). The overall mortality of intraluminal postpancreatoduodenectomy hemorrhage patients was 6.1%. The bleeding sources were identified in 63 patients (54.8%), among whom 33 (28.7%) were diagnosed as "false" intraluminal postpancreatoduodenectomy hemorrhage because of primary extraluminal hemorrhage. Multivariate analyses suggested that high body mass index (odds ratio, 1.30; 95% confidence interval, 1.06-1.58; P = .010) was an independent risk factor for "false" intraluminal postpancreatoduodenectomy hemorrhage. Angiography demonstrated superior localization of bleeding sources (65.3%) compared with endoscopy (32.7%) and computed tomography (26.1%) (P < .001), with a lower false-positive rate than relaparotomy (2.0% vs 17.5%, P = .030). Definitive hemostasis rate was comparable between angiography (44.9%) and relaparotomy (50.0%), both significantly outperforming endoscopy (21.2%, P = .008). CONCLUSION:"False" intraluminal postpancreatoduodenectomy hemorrhage represents a significant subset of intraluminal postpancreatoduodenectomy hemorrhage cases. Angiography may serve as a reliable tool for both the diagnosis and treatment of intraluminal postpancreatoduodenectomy hemorrhage, particularly when "false" intraluminal postpancreatoduodenectomy hemorrhage is highly suspected.
The aim of our study was to determine the outcomes of liver transplant recipients receiving either lamivudine (LAM) monotherapy or LAM combined with low-dose intramuscular (IM) hepatitis B Immunoglobulin (HBIG) therapy. We performed a retrospective review of the medical records of patients that had had liver transplantation in a single center for HBV-related liver diseases from December 1999 to June 2004. A total of 165 patients received LAM monotherapy (51 patients) or combined prophylaxis (114 patients) post-liver transplantation (LT) with a mean follow-up of 20.13 months. Hepatitis B relapsed in 21 patients of the hepatitis B surface antigen (HBsAg) carriers who received LAM monotherapy, with a 1- and 2-yr actuarial risk of 27.4% and 39.7%. Recurrence occurred in 16 patients of 114 patients receiving the combined prophylaxis, with a 1- and 2-yr recurrence rate of 13.5% and 15.2% (P = 0.024). A total of 25 cases (67.6%) with YMDD mutants were detected in all the 37 patients, 14 cases (66.7%) in the monotherapy group and 11 cases (68.8%) in the combination group. In conclusion, LAM and low-dose intramuscular HBIG treatment demonstrates a better result than LAM monotherapy, as prophylaxis against post-LT reinfection of the graft, but the safety and efficacy as a substitution for high-dose intravenous HBIG with LAM needs to be investigated further.
571 Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy in hepatocellular carcinoma (HCC). Among BCLC A/B patients (pts) with MVI, adjuvant transarterial chemoembolization has been reported to provide a 1-year recurrence-free survival (RFS) rate of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with a PD-1 inhibitor as adjuvant therapy for pts at high risk of recurrence. Herein, we present the updated results with a median follow-up of 11.6 months. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and presented with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) More than three tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of the main portal venous system were excluded. Donafenib combined with a PD-1 inhibitor (i.e., toripalimab) was initiated at 4 to 8 weeks post-resection and was to be continued for up to six months, unless recurrence occurred or there was an intolerable adverse reaction. No other adjuvant therapies were permitted before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFS rate. The secondary endpoints included overall survival, quality of life (QoL) measured with the FACT- Hepatobiliary questionnaire, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in the efficacy analysis. The median time from surgery to enrollment was 1.4 months. MVI was the most common risk factor (n=25, 92.6%). The majority of the pts had only one risk factor (n=23, 85.2%). As of the data cutoff on August 13, 2024, relapse had occurred in four pts and the median RFS was not reached. The 1-year RFS rate was 81.6% (90% CI, 67.8%-95.4%) in all evaluable pts. QoL showed a mild increase from baseline while on adjuvant therapy. No deaths were observed. In the 30 pts who had received at least one dose, the incidence of any grade and grade 3 treatment-related adverse events (TRAEs) were 90.0% (27/30) and 40.0% (12/30), respectively. No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurring in at least two pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), increased alanine aminotransferase (10.0%), and increased aspartate aminotransferase (6.7%). Conclusions: The study's duration exceeded expectations due to slow recruitment. Nonetheless, it showed a promising outcome with a regimen of 6 months of adjuvant therapy with donafenib plus toripalimab in BCLC A/B pts at high risk of recurrence. An improvement in QoL was observed among patients during the adjuvant therapy. No new safety issues were identified. Clinical trial information: NCT04418401 .
BACKGROUND Portal vein stenosis (PVS) is a prevalent complication following pediatric liver transplantation (pLT) and significantly impacts long-term graft outcomes. This study assessed the efficacy and safety of balloon angioplasty and stent placement, calculated rates of restenosis or reintervention, and determined optimal interventional strategies for managing PVS following pLT. MATERIAL AND METHODS We retrospectively analyzed 884 pLT recipients at our institution. PVS occurred in 67 patients; 64 successfully underwent interventional procedures. We comparatively analyzed patients who achieved satisfactory results following initial balloon angioplasty with those who required subsequent interventions. Factors, including history of portal vein bridging and donor-recipient portal vein discrepancy rate, were analyzed. Significant factors were used to develop a logistic regression-based risk prediction model. Kaplan-Meier curves estimated patient and graft survival rates. RESULTS Fifty-two patients (81.25%) demonstrated satisfactory recovery following initial balloon angioplasty among the 64 pLT recipients with PVS. Twelve patients had restenosis; 10 underwent subsequent interventions with successful outcomes. A comparative analysis between the initial balloon angioplasty success group and the reintervention group showed significant differences between the groups with respect to portal vein bridging history and portal vein discrepancy rate (P<0.05). A logistic regression-based prediction model for restenosis was established. Kaplan-Meier survival analysis indicated an overall patient survival rate of 98.5% and a graft survival rate of 92.5% during the study period. CONCLUSIONS Patients with portal vein bridging history or poor donor-recipient PV matching are more prone to restenosis after initial balloon angioplasty. For such cases, we recommend direct stent placement as the initial treatment strategy.
Peri-operative respiratory virus (RV) infection is critical in paediatric liver transplantation. However, it has been inadequately studied, especially in terms of the clinical latency of infection (incubation period) and Omicron variant infection. Herein, we compared the infection profile of common RVs and Omicron variants in paediatric liver transplantation, aiming to identify the association of virus infection with outcomes. The Omicron cohort was designed prospectively, and the RV cohort was retrospective. Survival outcomes, medical resources, and major complications were compared. Risk factors associated with peri-operative mortality were investigated using regression analysis. We enrolled 649 paediatric liver transplantation patients, including 28 Omicron and 61 RV infections. The 1-y overall survival was 97.7 ± 0.6% for the non-infected group, and 93.4 ± 3.2% for the RV group (p = 0.092). No death occurred in the Omicron group. Mortality was higher in the clinical latency infection group compared with that in the non-infected group (13.8% vs. 1.4%, p = 0.002). Latent RV infection (hazard ratio (HR) = 6.323, 95% confidence interval (CI): 1.374-29.087), Multi‑drug resistance organism pneumonia (HR = 7.177, 95% CI: 1.817-28.350), infectious shock (HR = 4.284, 95% CI: 0.995-18.442) and blood loss (HR = 3.209, 95% CI: 1.166-8.833) were independent risk factors for peri-operative mortality. In conclusion, pre-transplant viral screening is fundamental to paediatric liver transplantation. Peri-operative Omicron infection might be controllable, while RV infection led to more complications compared with those in the non-infected group. Clinical latency infection is the key risk for paediatric liver transplantation mortality.
The incidence of post-transplant poral vein stenosis (PVS) is higher in pediatric liver transplantation, probably resulting from various portal vein (PV) reconstruction methods or other factors. 332 patients less than 12 years old when receiving liver transplantation (LT) were enrolled in this research. Portal vein reconstruction methods include anastomosis to the left side of the recipient PV trunk (type 1, n = 170), to the recipient left and right PV branch patch (type 2, n = 79), using vein graft interposition (type 3, n = 32), or end-to-end PV anastomosis (type 4, n = 50). The incidence of PVS was analyzed in terms to different PV reconstruction methods and other possible risk factors. PVS occurred in 35 (10.5
Background: Pancreatic fistula after distal pancreatectomy is a common and potentially lethal complication. The optimal closure method for the pancreatic remnant during minimally invasive distal pancreatectomy (MDP) remains unclear. Methods: Data of consecutive patients who underwent MDP in our institution between July 2018 and June 2021 were collected. The outcomes of MDP with stapler and hand-sewn closure were compared. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF) per the International Study Group of Pancreatic Surgery definition. Results: Of the 384 patients (stapler closure, 339; hand-sewn closure, 45) enrolled, 249 developed CR-POPF (grades B and C: 242 and 7 patients, respectively). The rates of grade B and grade C POPF in the stapler group were similar to the corresponding rates in the hand-sewn group (64.6% and 1.5% vs 51.1% and 4.4%, P = .078 and P = .223, respectively). No differences between the stapler and hand-sewn groups were observed regarding the median operation time (207 vs 222 minutes, P = .139), incidence of major complications (16.5% vs 20.0%, P = .559), and mortality (0.2% vs 0%, P = 1.000). The independent risk factors of CR-POPF were abdominal abscess, prolonged operation time, and transection site (P = .004, .006, and .001, respectively). Conclusion: The incidence and severity of CR-POPF by stapler closure of the pancreatic stump were comparable to those associated with hand-sewn closure in MDP in this retrospective cohort. Randomized controlled trials are needed to verify this finding.
AbstractEvidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.
e16202 Background: Adjuvant therapy may have an important role in decreasing recurrence rates and improve survival in selected pts with HCC following surgical resection. However, there is no standard treatment options or strategies. This study aimed to investigate the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC pts with high risks of recurrence. Methods: This prospective, open-label, single-arm study planned to enroll 30 pts who had undergone radical surgery and were diagnosed as HCC confirmed by histology or cytology with any of the following risk factors: a) Microvascular invasion (MVI); b) Satellite nodules in specimens; c) >3 tumor nodules; d) Portal vein tumor thrombosis (excluded main portal vein invasion). Donafenib combined with anti-PD-1 antibody was initiated at 4 to 8 weeks after surgical resection and continued for up to six months. The primary endpoint was the cumulative 1-year recurrence-free survival rate (RFSR). The secondary endpoints were recurrence-free survival (RFS), overall survival, and safety. Results: As of December 31st, 2022, a total of 23 pts received donafenib plus anti-PD-1 antibody (toripalimab) with a mean follow-up of 7.6 months (safety set). The most common risk factor was MVI (91%). 20 pts were included in efficacy set (three pts were excluded due to ineligibility), of whom 16 pts had one risk factor and four had two. Intrahepatic recurrence occurred in 3 pts (15%) and no extrahepatic metastasis or death was reported. The RFSR at one year was 83.0% (90%CI, 61.6%-93.1%) in all the pts from efficacy set, 81.9% (90%CI, 59.6%-92.6%) and 92.3% (90%CI, 66.0%-98.5%) in pts with MVI and MVI-low risk, and 85.1% (90%CI, 59.6%-95.1%) in pts with only one risk factor. The median RFS was not reached. The incidence of grade 3 adverse events related to donafenib and/or toripalimab was 52.2% (12/23). No pts had grade 4/5 adverse events. Adverse events leading to withdrawal of any and both treatments occurred in six (26.1%) and one (4.3%) pts, respectively. The most common grade 3 treatment-related adverse events (occurred in more than one patient) were palmar-plantar erythrodysesthesia syndrome (17.4%), rash (17.4%), alanine aminotransferase increased (13.0%), and aspartate aminotransferase increased (8.7%). Conclusions: These results were consistent with earlier reports. The combination of donafenib and toripalimab may be a promising adjuvant therapy for pts with MVI, satellite nodules or multiple tumor after hepatectomy. No safety issues were noted. Clinical trial information: NCT04418401 . [Table: see text]
Background and aims: Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival.Methods: This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. Delta MELD and Delta CLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality.Results: Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (Delta CLIF-OF >= 2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for Delta CLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to Delta MELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), Delta CLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while Delta CLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D).Conclusion: This was the first ACLF-based dynamic evaluation study. Delta CLIF-OF was a more powerful predictor of post-LT mortality than Delta MELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, Delta CLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.
Background and aims:. Many patients with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A exceeding the Milan criteria, or of BCLC stage B, can undergo resection after successful preoperative therapy, but an optimal approach has not been identified. We investigated preoperative drug-eluting bead transarterial chemoembolization (DEB-TACE) plus sintilimab, in this setting. Approach and Results:. In this prospective, phase II study (NCT04174781), adults with HCC of BCLC stage A exceeding the Milan criteria, or BCLC stage B, and ineligible for surgical resection, received sintilimab 200 mg and DEB-TACE. The primary endpoint was progression-free survival by modified RECIST. Secondary endpoints included objective response rate, pathologic response rate, and safety. At the data cutoff (July 2022), among 60 patients, the objective response rate was 62% (37/60) and 51 patients had undergone surgery. After a median follow-up of 26.0 months (range, 3.4–31.8), the median progression-free survival was 30.5 months (95% CI: 16.1–not reached). Among patients undergoing surgery, median progression-free survival was not reached and the 12-month progression-free survival rate was 76% (95% CI: 67–91). A pathologic complete response was achieved in 14% (7/51) of these patients. All patients experienced at least one adverse event, but these were generally manageable. Exploratory analyses showed an association between cytokeratin, V-domain Ig-containing Suppressor of T-cell Activation, CD68, CD169, and cluster 13 fibroblasts and recurrence after surgery. Conclusions. Sintilimab plus DEB-TACE before surgery showed good efficacy and safety in patients with HCC of BCLC stage A exceeding the Milan criteria or BCLC stage B.
Objective:To achieve radical resection of locally advanced pancreatic ductal adenocarcinoma (PDAC), and tested the safety and benefits of intestinal autotransplantation in pancreatic surgery.Background:PDAC has an extremely dismal prognosis. Radical resection was proved to improve the prognosis of patients with PDAC; however, the locally advanced disease had a very low resection rate currently. We explored and evaluated whether the combination of modern advances in systemic treatment and this macroinvasive surgery was feasible in clinical practice.Methods:Patients diagnosed as PDAC with superior mesenteric artery involvement and with or without celiac trunk involvement were included. Patients were treated with modified-FOLFIRINOX chemotherapy with or without anti-PD-1 antibodies and were applied to tumor resection combined with intestinal autotransplantation. Data on operative parameters, pathologic results, mortality, morbidity, and survival were analyzed.Results:A total of 36 consecutive cases were applied to this strategy and underwent radical resection combined with intestinal autotransplantation. Among these patients, 24 of them received the Whipple procedure, 11 patients received total pancreatectomy, and the other 1 patient received distal pancreatectomy. The median operation time was 539 minutes. Postoperative pathology showed an R0 resection rate of 94.4%, and tumor invasion of a superior mesenteric artery or superior mesenteric vein was confirmed in 32 patients. The median number of dissected lymph nodes was 43, and 25 patients were positive for lymph node metastasis. The median time of intensive care unit stay was 4 days. Two patients died within 30 days after surgery due to multiorgan failure. The severe postoperative adverse events (equal to or higher than grade 3) were observed in 12 out of 36 patients, and diarrhea, gastroparesis, and abdominal infection were the most frequent adverse events. Postoperative hospital stay was averagely of 34 days. The recurrence-free survival is 13.6 months. The median overall survival of patients after diagnosis and after surgery was 21.4 months and 14.5 months, respectively.Conclusions:Our attempt suggests the safety of this modality and may be clinically beneficial for highly selected patients with PDAC. However, the experience in multidisciplinary pancreatic cancer care and intestinal transplantation is warranted.
Background With the advent of intensive combination regimens, an increasing number of patients with unresectable pancreatic cancer (UPC) have regained the opportunity for surgery. We investigated the clinical benefits and prognostic factors of conversion surgery (CS) in UPC patients. Methods We retrospectively enrolled patients with UPC who had received CS following first-line systemic treatment in our center between 2014 to 2022. Treatment response, safety of the surgical procedure and clinicopathological data were collected. We analyzed the prognostic factors for postoperative survival among UPC patients who had CS. Results Sixty-seven patients with UPC were enrolled (53 with locally advanced pancreatic cancer (LAPC) and 14 with metastatic pancreatic cancer (MPC)). The duration of preoperative systemic treatment was 4.17 months for LAPC patients and 6.52 months for MPC patients. All patients experienced a partial response (PR) or had stable disease (SD) preoperatively according to imaging. Tumor resection was unsuccessful in four patients and, finally, R0 resection was obtained in 81% of cases. Downstaging was determined pathologically in 87% of cases; four patients achieved a complete pathological response. Median postoperative-progression-free survival (PO-PFS) was 9.77 months and postoperative overall survival (PO-OS) was 31.2 months. Multivariate logistic regression analyses revealed that the resection margin and postoperative changes in levels of tumor markers were significant prognostic factors for PO-PFS. No factors were associated significantly with PO-OS according to multivariate analyses. Conclusions CS is a promising strategy for improving the prognosis of UPC patients. The resection margin and postoperative change in levels of tumor markers are the most important prognostic factors for prolonged PFS. Multidisciplinary treatment in high-volume centers is strongly recommended. Prospective studies must be undertaken to resolve the various problems regarding optimal regimens, the duration of treatment, and detailed criteria for CS.
BACKGROUND:For tumors in the neck and body of the pancreas, distal pancreatectomy (DP) has been the standard surgical procedure for the last few decades and central pancreatectomy (CP) is an alternative surgical option. Whether CP better preserves remnant pancreatic endocrine and exocrine functions after surgery remains a subject of debate.AIM:To evaluate the safety and efficacy of CP compared with DP for benign or low-grade malignant pancreatic tumors in the neck and body of the pancreas.METHODS:This retrospective study enrolled 296 patients who underwent CP or DP for benign and low-malignant neoplasms at the same hospital between January 2016 and March 2020. Perioperative outcomes and long-term morbidity of endocrine/exocrine function were prospectively evaluated.RESULTS:No significant difference was observed in overall morbidity or clinically relevant postoperative pancreatic fistula between the two groups (P = 0.055). Delayed gastric emptying occurred more frequently in the CP group than in the DP group (29.4% vs 15.3%; P < 0.005). None of the patients in the CP group had new-onset or aggravated distal metastasis, whereas 40 patients in the DP group had endocrine function deficiency after surgery (P < 0.05). There was no significant difference in the incidence of diarrhea immediately after surgery, but at postoperative 12 mo, a significantly higher number of patients had diarrhea in the DP group than in the CP group (0% vs 9.5%; P < 0.05).CONCLUSION:CP is a generally safe procedure and is better than DP in preserving long-term pancreatic endocrine and exocrine functions. Therefore, CP might be a better option for treating benign or low-grade malignant neoplasms in suitable patients.
Background and Aim Donor shortage has become worldwide limitation in liver transplantation (LT). Use of hepatitis B virus surface antigen positive (HBsAg+) donors could be an alternative source of donor organs. This study aims to investigate the safety and efficacy of LT using HBsAg+ liver grafts and associated long-term outcome. Methods This was a retrospective study of adults LT registered in the database of the China Liver Transplant Registry between January 2015 and September 2018. By propensity score matching (1:1), 503 eligible patients who received HBsAg+ liver grafts were compared with 503 matched patients who received HBsAg- liver grafts. Results The 1-, 3-, and 5-year patient survival rates were 81.52%, 72.04%, and 66.65% in HBsAg+ donor group, which were comparable with 83.93%, 77.27%, and 65.73% in HBsAg- donor group (P = 0.222). The 1-, 3-, and 5-year graft survival rates were also comparable between the two groups (81.49%, 71.45%, and 67.26% vs 83.62%, 77.11%, and 65.81%, respectively, P = 0.243). Most main complications were not increased in HBsAg+ donor group except for the retaining of HBsAg positivity after LT. Furthermore, transplanting HBsAg+ liver grafts did not result in inferior outcomes either in HBsAg+ or HBsAg- recipients. The risk of tumor recurrence after LT was not increased in hepatocellular carcinoma patients. Conclusions The outcomes of using HBsAg+ liver grafts were comparable with those of HBsAg- liver grafts. Our study provided strong evidence for the safe use of HBsAg+ grafts in LT to expand the donor liver pool.
560 Background: FOLFIRINOX or modified FOLFIRINOX (mFFX) is the standard of care for the first line treatment of metastatic pancreatic adenocarcinoma (PDAC). However, the prognosis still remains poor, novel treatment options are urgently need. Sintilimab, a human IgG4 monoclonal antibody that binds to programmed cell death receptor-1(PD-1), has shown remarkable efficacy in various cancers. We designed the CISPD3-trial in China, aimed to determine the efficacy and safety of the combination of Sintilimab and mFFX for metastatic or recurrent PDAC. Methods: In this single center, randomized, open-label, phase 3 trial, we enrolled patients with metastatic or recurrent PDAC to compare the efficacy and safety of Sintilimab combined with mFFX versus mFFX alone as first-line or second-line therapy. Patients eligible were randomly assigned (1:1) to Sintilimab (200 mg every 3 weeks) plus mFFX (irinotecan 85 mg/m2, oxaliplatin 68 mg/m2 followed by 5-FU 2400 mg/m2, every 2 weeks) or mFFX. The primary endpoint was overall survival (OS), secondary endpoints included progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov, NCT03977272. Results: From March 2019, to Dec 2020, 110 patients were enrolled and randomized to Sintilimab plus mFFX (n = 55) or mFFX (n = 55). 85.5% Patients had metastatic disease and 14.5% had recurrent disease, 7.3% Patients had previous first-line chemotherapy. The baseline characteristics of the subjects in these two arms were comparable. The median follow-up time for OS was 21.3 months (IQR 15.9-25.0) in Sintilimab plus mFFX group and 19.6 months (15.5-25.1) in mFFX group. The median OS was similar between Sintilimab plus mFFX (10.9 months) and mFFX arm (10.8 months) with HR = 1.083 (95% CI 0.6843 to 1.690). Median PFS was 5.9 months in Sintilimab plus mFFX arm and 5.73 months in mFFX arm (HR 0.9324, 95% CI, 0.6158 to 1.412). The ORR was 50% in the Sintilimab plus mFFX arm versus 23.9% in the mFFX arm (P = 0.010). The most common AE of Grade ≥ 3 are neutropenia (58.5% in the Sintilimab plus mFFX group vs. 44.4% in mFFX group), thrombocytopenia (17.0% vs. 11.1%), anemia (13.2% vs. 13.0%), vomiting (13.2% vs. 11.1%), increased aminotransferase (11.3% vs. 5.6%). 22.6% immune-related adverse events (irAEs) and 5.7% irAEs of grade ≥ 3 were observed in Sintilimab plus mFFX arm. The most common irAEs were pulmonary adverse event (13.2%) with 3 (5.7%) patients grade ≥ 3, among which 1 (1.8%) death was considered to be treatment-related. No new safety signals were identified. Conclusions: The addition of Sintilimab to mFFX improved ORR in advanced PDAC patients significantly, however no superior OS and PFS were observed. Toxicity was manageable. These data suggest that combined PD-1 blockade may expand the benefit of chemotherapy in PDAC. Clinical trial information: NCT03977272.
Background: The growing disparity between organ availability and the number of candidates for organ transplantation has urged the use of marginal grafts including grafts from syphilis-positive donors. However, few knowledges could be acknowledged about this due to the rare data from case reports. Therefor we evaluate our data and summarize our experience of the management of liver grafts from syphilis-positive donors. Methods: From January 2015 to December 2019, 22 adult patients received liver transplantation from syphilis-positive donors while 873 patients got liver transplantation from syphilis-negative donors at our center. Given the imbalance in several baseline variables, propensity score matching was used. The outcomes were compared including complications, hospital stay, recovery of liver function and survival of the two groups and the management of the recipients was reviewed. Results: There were no differences in complications and hospital stay of the recipients after transplantation. And it showed similar trends in the liver function recovery. Patient and graft survivals were comparable to that of syphilis-negative grafts. And benzathine penicillin is effective to protect the recipients from syphilis. Conclusions: The use of liver grafts from syphilis-positive donors does not to increase the morbidity and mortality of the recipients. Also, the prophylactic theory of benzathine penicillin is helpful.
Objective: This study was performed to compare the effect of different time intervals between endoscopic retrograde cholangiopancreatography (ERCP) and early laparoscopic cholecystectomy (LC) on the operation duration, postoperative hospitalization, and postoperative complications. Materials and methods: We retrospectively reviewed data for 105 patients with cholecystocholedocholithiasis who underwent ERCP and LC from January 2016 to May 2019. The patients were divided into three groups. In Group A, the interval from ERCP to LC was ≤3 days; in Group B, the interval was 4–6 days; and in Group C, the interval was >6 days. We compared operation duration, blood loss volume, postoperative hospitalization, and rate of biliary complications among the three groups and analyzed the risk factors for postoperative complications. Results: Operation duration differed significantly between Groups A and B (47.5 min vs. 60.0 min, p = 0.033) and between Groups B and C (60.0 min vs. 47.5 min, p = 0.033). The median blood loss volume was significantly less in Group A than in Group B (8 ml vs. 10 ml, p = 0.041), and the postoperative hospitalization and rate of postoperative complications did not differ significantly. Conclusion: The best time for patients with cholecystocholedocholithiasis to undergo LC is 0–3 days after ERCP. If the operation cannot be performed within 3 days, we recommend 6 days after ERCP.
Background: Metastasis is the primary cause of death in colorectal cancer (CRC); the underlying mechanisms remain partly unknown. In this study, we aim to investigate the value of HOXA11-AS in survival evaluation and the potential role of HOXA11-AS/miR-149-3p axis in the CRC metastasis. Methods: The expressions of HOXA11-AS, both in obtained CRC samples and adjacent noncancerous tissues, were analyzed in survival evaluation. Competing endogenous RNAs (CeRNAs) Analysis were employed to reveal the potential relationship between HOXA11-AS and miR-149-3p. It was further confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Dual-luciferase reporter assay. Migration and invasion assay were used to verify the potential role of HOXA11-AS and miR-149-3p in the regulation of CRC metastasis. The potential pathway was explored by Western blot analysis. Results: The expression of HOXA11-AS in the CRC tissue is significantly higher than the expression in adjacent noncancerous tissue (p<0.0001). High expressions of HOXA11-AS were noticeably correlated with clinicopathologic characteristics including advanced clinical stage (p=0.021), larger tumor size (p<0.001) and frequent tumor recurrence (p=0.001). The overall survival in HOXA11-AS-High group was significantly shorter than the HOXA11-AS-Low group (p<0.001). Advanced clinical stage, tumor size and high expression of HOXA11-AS were showed as independent prognostic prediction factors for the 5-year tumor relapse of CRC patients (p<0.001). HOXA11-AS acts as a potential molecular sponge for miR-149-3p, in the promotion of CRC metastasis. In the miR-149-3p mimic-treated group, the expression of E-cadherin was increased, whereas the expression of N-cadherin, Snail, Slug, TGF-β1, Wnt2b, Twist and C/EBPβ was decreased. Conclusion: This study demonstrates that high expression of HOXA11-AS is correlated with CRC progression and poor prognosis and may promote metastasis via EMT by modulating miR-149-3p.
Background: Resection of pancreatic ductal adenocarcinoma (PDAC) with synchronous liver metastasectomy is still a matter of debate. We aimed to evaluate the feasibility of synchronous resection of PDAC and liver metastases for curative intent at a high-volume surgical center. Methods: Patients who underwent pancreaticoduodenectomy (PD) with synchronous liver metastasectomy (M1 resection group, n = 50) were matched 1 : 1 based on tumor and nodular stage, age, gender, body mass index and concomitant disease with two control groups (M0 resection and M1 no resection). The M0 resection group included patients who underwent PD without metastases. The M1 no resection group included patients with liver metastases who underwent palliative bypass or exploratory laparotomy without resection followed by palliative and adjuvant therapies. Results: M1 resection group had a longer operation time, larger intraoperative blood loss, and longer postoperative hospital stay than other two groups. R0 resection rate of M1 resection group was similar to that of M0 resection group (92% vs. 94%, p = 1.000). Postoperative complications were comparable between the groups. The overall median survival in M1 resection, M0 resection, and M1 no resection group was 16, 30, and 6 months, respectively. Cumulative survival rates for 1-, 2-, and 3-year of the M1 resection, M0 resection, and M1 no resection group were 63.8%, 29.0%, and 6.7%; 94.0%, 74.4%, and 25.1%; 24.0%, 2.0%, and 0%, respectively. The survival of M1 resection group was worse than that of M0 resection group (p = 0.009), however significantly much better than that of M1 no resection group (p = 0.001). Univariate analysis showed carcinoembryonic antigen >8 ng/ml and non-R0 resection were associated with death. Multivariate analysis revealed that M1 resection group had improved survival compared with M1 no resection group. Conclusions: PD with synchronous liver metastasectomy for oligometastatic PDAC is safe and feasible, it might provide survival benefits for selected patients.