Evaluation of structural and molecular variation of starch granules during the gelatinization process by using the rapid Mueller matrix imaging polarimetry system.

Starch is an essential and widely distributed natural material, but its detailed conformation and thermal transition properties are not yet well understood. We present a rapid Mueller matrix imaging system to explore the structural characteristics of starch granules by using 16 measurements with different incoming and outgoing polarizations. Due to the minimum rotation of the optical elements and the self-calibration ability of this system, the full Mueller matrix images can be accurately obtained within ten-odd seconds. Both structural and molecular features of the starch granule were investigated in the static state and gelatinization process by means of multiple optical characteristics deduced from the Mueller matrix. The experimental results for the structural changes during the gelatinization were close to other nonlinear optical approaches; moreover, the crystallinity and optical rotation of the starch granule are also determined through the use of this approach.

Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of patients with single-nodule small hepatocellular carcinoma following curative resection: a retrospective report.

BACKGROUND: Preoperative neutrophil-to-lymphocyte ratio (NLR) has been identified as a predictor for the recurrence of hepatocellular carcinoma (HCC), but the cut-off of NLR is inconsistent in various studies. Thus, we detected the prognostic value of preoperative NLR in the single-nodule small HCC (SHCC) patients using X-tile for cutpoint. METHODS: Between January 2007 and December 2010, a total of 222 single-nodule SHCC patients underwent curative resection and were examined for the prognostic roles of preoperative NLR by X-tile. RESULTS: In this study, all patients were divided into the low-NLR subgroup (NLR ≤ 2.1) and the high-NLR subgroup (NLR > 2.1) by X-tile. Preoperative NLR showed predictive value for time to recurrence (TTR) and overall survival (OS). Moreover, NLR was associated with total bilirubin, white blood cell counts, and HBsAg, respectively (P = 0.012, <0.001, and 0.011, respectively). Especially, NLR could discriminate the outcome of patients in the subgroup with alpha-fetoprotein (AFP) levels of ≤400 ng/mL. Importantly, postoperative transcatheter arterial chemoembolization (TACE) had close relationship with OS (P = 0.001) and TTR (P ≤ 0.001). CONCLUSIONS: Therefore, this study indicates that preoperative NLR, divided by X-tile for the cutpoint, is a simple prognostic marker for the patients with single-nodule SHCC after curative resection.

Conditional survival of pancreatic ductal adenocarcinoma in surgical and nonsurgical patients: a retrospective analysis report from a single institution in China.

BACKGROUND: Conditional survival (CS) could offer reliable prognostic information for patients who survived beyond a specified time since diagnosis when the impact of late effects have the greatest influence on prognosis. We aim to investigate CS for pancreatic ductal adenocarcinoma (PDAC) patients with surgery and nonsurgery. METHODS: Chinese PDAC patients between January 2002 and September 2012 were reviewed for analyses. CS rates were calculated for survivors after surgery and nonsurgery at different time points. RESULTS: Several clinicopathologic features were associated with overall survival (OS) in each subgroup including curative resection, palliative surgery, and nonsurgery. Both univariate and multivariate analyses showed that chemotherapy was a critical predictor for OS regardless of treatment status. CS rates were higher in the curative resected patients than other cases at the same time points. Importantly, stratification of 1-year CS by carcinoembryonic antigen (CEA), (carbohydrate antigen) CA19-9, and tumor stage showed lower CEA, CA19-9, and tumor stage associated with favorable 1-year CS over time (P = 0.016, 0.009 and 0.003). CONCLUSIONS: Dynamic CS estimates could be an accurate assessment for the prognosis of PDAC patients, allowing patients and clinicians to project subsequent survival based on time change.

Toripalimab Plus Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Trial.

PURPOSE: This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab in treating advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. Primary endpoints included safety and tolerability, and objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Fifty-four patients were enrolled between Apr 17, 2020 and Dec 11, 2020. As assessed by the investigator according to RECIST v1.1, the ORR was 31.5% [95% confidence interval (CI), 19.5-45.6] and the lower bound of the 95% CI was above the pre-specified boundary of 10%. The independent review committee (IRC) assessed ORR according to modified RECIST (mRECIST) was 46.3% (95% CI, 32.6-60.4). The median progression-free survival were 8.5 months (95% CI, 5.5-11.0) and 9.8 months (95% CI, 5.6-not evaluable) assessed by the investigator according to RECIST v1.1 and IRC according to mRECIST criteria, respectively. The median overall survival (OS) was not reached, and the 12- and 24-month OS rates were 77.3% and 63.5%, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 27 patients (50.0%). The most common TEAEs were proteinuria (59.3%), hypertension (38.9%), aspartate aminotransferase increased (33.3%), amylase increased (29.6%), platelet count decreased (27.8%), and bilirubin increased (27.8%). CONCLUSIONS: Toripalimab plus bevacizumab showed a favorable efficacy and safety profile, supporting further studies of this combination regimen as a first-line treatment of advanced HCC.

The combination of a prolonged treatment time window and alpha-fetoprotein benefits the tumor response of hepatocellular carcinoma patients as evaluated by the imRECIST: a single-center, retrospective study.

Background: The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. Methods: This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Results: Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). Conclusions: In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

Impact of simultaneous splenectomy and orthotopic liver transplantation in patients with end-stage liver diseases and splenic hyperfunction.

BACKGROUND: Whether splenectomy can be performed simultaneously during liver transplantation in patients with end-stage liver diseases complicated by hypersplenism remains controversial. This study aimed to compare the impact of simultaneous splenectomy on high- and low-risk liver transplant patients with end-stage liver diseases and severe hypersplenism. METHODS: Forty-two patients with end-stage liver diseases complicated by severe hypersplenism who had undergone orthotopic liver transplantation were enrolled in this study. Splenectomy was performed in 19 of the patients. The 42 patients were grouped according to the risk of liver diseases and operations they received. Patients were considered to be at high-risk if they had at least one of the following conditions: preoperative prothrombin time >5 seconds, portal vein thrombosis, and severe perisplenitis. High-risk patients who had undergone splenectomy were classified into group A, whereas high-risk patients who had not undergone splenectomy were classified into group B. Low-risk patients who had undergone splenectomy were classified into group C, and low-risk patients who had spleen preservation were classified into group D. Operative time, intraoperative blood loss, postoperative bleeding, pulmonary infection, perioperative mortality, and postoperative platelet recovery were analyzed. RESULTS: Operative time and intraoperative blood loss were greater in group A than in groups B-D (P<0.01), but there was no significant difference between groups C and D (P>0.05). In group A, 3 patients had postoperative bleeding, 5 had pulmonary infection, and 2 had perioperative mortality, which was higher than any other group, but postoperative bleeding, pulmonary infection, and perioperative mortality were similar to those in groups C and D. In patients undergoing simultaneous splenectomy, platelet counts recovered within 6 months after surgery. Thrombocytopenia was sustained in 3 of the 23 patients who did not undergo simultaneous splenectomy. CONCLUSION: Splenectomy should be avoided during orthotopic liver transplantation in high-risk patients, but this procedure does not increase the operative risk in low-risk patients and may be a valuable method to ensure good postoperative platelet recovery.

Lipocalin2 as a useful biomarker for risk stratification in patients with acute cholangitis: A single-center prospective and observational study.

BACKGROUND: Lipocalin2 (LCN2) is being increasingly used to diagnose and predict severe bacterial infection. We aimed to evaluate the predictive value of serum lipocalin 2 for severity grading of acute cholangitis (AC) on patient admission. METHODS: A total of 108 patients were enrolled in this study. Blood samples were obtained at admission. Receiver operating characteristic (ROC) curves were built to assess the abilities of LCN2 levels to predict moderate/severe (vs. mild) or severe (vs. mild/moderate) AC with traditional markers of inflammation such as white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR). The correlations among the key research indicators were determined using spearman's test. Multivariate analysis was conducted to identify the risk factors for severe AC. RESULTS: The levels of LCN2 on admission increased significantly with the severity of AC. By analysis of ROC curve of biomarkers for differentiating patients with moderate to severe AC (versus mild AC), the AUC for LCN2 (0.925) was significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 262.2 ng/mL, with a sensitivity of 90.8% and specificity of 81.4%. In addition, the AUC for LCN2 (0.912) for severe acute cholangitis was also significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 325.7 ng/mL. The sensitivity and specificity were 86.1% and 83.3%, respectively. Furthermore, LCN2 the closest relationships were found between LCN2 and PCT (r = 0.8054, P < 0.001) through Spearman's test. Multivariate analysis showed that LCN2 was the only risk factor predicting severe AC (P < 0.05). CONCLUSION: Serum LCN2 concentration on patient admission could better predict severe acute cholangitis than WBC, CRP, PCT and NLR. Serum LCN2 may become a potential biomarker in the risk stratification of acute cholangitis and in indicating the time of biliary drainage.

Comparison of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic radical antegrade modular pancreatosplenectomy (l-RAMPS) provides a new surgical approach for patients with pancreatic cancers of the body and tail. However, whether it can achieve comparable outcomes to the open RAMPS (o-RAMPS) remains an issue. METHODS: To evaluate the safety and effectiveness of l-RAMPS, the studies in the databases of Medline, Embase, and the Cochrane Library published before September 13, 2021 were searched and a meta-analysis was performed using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. The perioperative and oncological outcomes were analyzed. RESULTS: Five retrospective cohorts involving 189 patients were included for final pooled analysis. There were no significant differences in the patients' operation time, intra-abdominal bleeding rate, intra-abdominal infection rate, mild morbidity (Clavien-Dindo classification = 1), moderate to severe morbidity (Clavien-Dindo classification ≥2), overall morbidity, wound infection rate, pancreatic fistula rate, delayed gastric emptying rate, reoperation rate, length of hospital stay, postoperative mortality, R0 resection rate, and 2-year overall survival between the 2 approaches. Besides, l-RAMPS was associated with less blood loss (mean difference (MD) = -232.69, 95% confidence interval (CI) = -316.93 to -148.46, P < 0.00001) and shorter days until oral feeding (MD = -0.79, 95% CI = -1.35 to -0.22, P = 0.006). However, the pooled analysis also indicated a significantly fewer lymph nodes dissected (MD = -3.01, 95% CI = -5.59 to -0.43, P = 0.02) in l-RAMPS approach. CONCLUSIONS: Although l-RAMPS provides similar outcomes associated with benefits of minimal invasiveness compared to o-RAMPS, it harvested significantly fewer lymph nodes which might have potentially negative influence on the patients' long-term survival. L-RAMPS is still in the infancy stage and further investigation is needed to verify its feasibility.

Chinese Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021 Edition).

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the "Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)" based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.

Clinical application of "Double R" anastomosis technique in laparoscopic pancreaticoduodenectomy procedure.

ABSTRACT: Laparoscopic pancreaticoduodenectomy (LPD) is widely used as a treatment for periampullary tumors and pancreatic head tumors. However, postoperative pancreatic fistula (POPF), which significantly affects mortality and length of hospital stay of patients, remains one of the most common and serious complications following LPD. Though numerous technical modifications for pancreaticojejunostomy (PJ) have been proposed, POPF is still the "Achilles heel" of LPD.To reduce POPF rate and other postoperative complications following LPD by exploring the best approach to manage with the pancreatic remnant, a novel duct-to-mucosa anastomosis technique named Double Layer Running Suture (Double R) for the PJ was established. During 2018 and 2020, a totally 35 patients who underwent LPD with Double R were included, data on the total operative time, PJ duration, estimated blood loss, recovery of bowel function, postoperative complications, and length of hospital stay were collected and analyzed.The average duration of surgery was (380 ±â€Š69) minutes. The mean time for performing PJ was (34 ±â€Š5) minutes. The average estimated blood loss was (180 ±â€Š155) mL. The overall POPF rate was 8.6% (3/35), including 8.6% (3/35) for the biochemical leak, 0% (0/35) for Grade B, and 0% (0/35) for Grade C. No patient suffered from biliary fistula, post-pancreatectomy hemorrhage, and intra-abdominal infection, the 30-day mortality was 0%.Double R anastomosis is potentially a safe, reliable, and rapid anastomosis with a low rate of POPF and post-pancreatectomy hemorrhage. It provides surgeons more options when performing LPD. However, its safety and effectiveness should be verified further by a larger prospective multicenter study.

Endoscopic Endoluminal Radiofrequency Ablation and Single-Operator Peroral Cholangioscopy System (SpyGlass) in the Diagnosis and Treatment of Intraductal Papillary Neoplasm of the Bile Duct: A Case Report and Literature Review.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare biliary benign tumor with atypical clinical features and is frequently misdiagnosed. Its treatment is limited and surgical resection is thought to be the only therapeutic option in patients with IPNB. With the aim of increasing the early diagnosis rate of IPNB and providing more therapeutic options for surgeons, we innovatively put forward the concept of combined utilization of SpyGlass and endoscopic endoluminal radiofrequency ablation (ERFA) in the diagnosis and treatment of IPNB. Case Presentation: An 85-year-old woman was referred to our hospital due to right upper quadrant abdominal pain. The image examinations indicated suspicious filling defects at the upper common bile duct. Further evaluation of SpyGlass cholangioscopy showed multiple reddish villous lesions at the left hepatic duct, and SpyBite biopsy under direct visualization demonstrated papillary low-grade dysplasia. In consideration of the advanced age and preference of the patient, the novel ERFA therapy was performed. The procedure was successful without periprocedural complications; the patient recovered uneventfully and was discharged 2 days after the operation. Upon follow-up, the patient was asymptomatic and in good physical condition at 8 months postoperatively. Conclusion: Preliminarily, we demonstrate that the strategy of a combination of SpyGlass and ERAF seems to be a promising, feasible, well-tolerated, and safe management for patients with IPNB. However, more data with larger patient volumes are needed to evaluate its outcomes further.

Minimally invasive versus open radical resection surgery for hilar cholangiocarcinoma: Comparable outcomes associated with advantages of minimal invasiveness.

BACKGROUND: Minimally invasive surgery (MIS) provides a new approach for patients with hilar cholangiocarcinoma (HCCA). However, whether it can achieve similar outcomes to traditional open surgery (OS) remains controversial. METHODS: To assess the safety and feasibility of MIS for HCCA, a systematic review and meta-analysis was performed to compare the outcomes of MIS with OS. Seventeen outcomes were assessed. RESULTS: Nine studies involving 382 patients were included. MIS was comparable in blood transfusion rate, R0 resection rate, lymph nodes received, overall morbidity, severe morbidity (Clavien-Dindo classification > = 3), bile leakage rate, wound infection rate, intra-abdominal infection rate, days until oral feeding, 1-year overall survival, 2-year overall survival and postoperative mortality with OS. Although operation time was longer (mean difference (MD) = 93.51, 95% confidence interval (CI) = 64.10 to 122.91, P < 0.00001) and hospital cost (MD = 0.68, 95% CI = 0.03 to 1.33, P = 0.04) was higher in MIS, MIS was associated with advantages of minimal invasiveness, that was less blood loss (MD = -81.85, 95% CI = -92.09 to -71.62, P < 0.00001), less postoperative pain (MD = -1.21, 95% CI = -1.63 to -0.79, P < 0.00001), and shorter hospital stay (MD = -4.22, 95% CI = -5.65 to -2.80, P < 0.00001). CONCLUSIONS: The safety and feasibility of MIS for HCCA is acceptable in selected patients. MIS is a remarkable alternative to OS for providing comparable outcomes associated with a benefit of minimal invasiveness and its application should be considered more.

Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. METHOD: A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. RESULTS: Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. CONCLUSIONS: LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.

[Association between RsaI and AluI polymorphism in the estrogen receptor beta gene and primary hepatocellular carcinoma.].

OBJECTIVE: To investigate whether there is a association between estrogen receptor beta (ERb) gene polymorphism and primary hepatocellular carcinoma (HCC). METHODS: 100 primary HCC patients and 100 controls from southwestern China were recruited in this study. The polymorphism of RsaI and AluI in ERb gene was analyzed by PCR- restriction fragment length polymorphism (RFLP). RESULTS: R allelic frequency was 35.0% and 51.0% in HCC patients and in control group, respectively, odds ratio (OR) was 0.517 [95% confidence intervals (CI) = 0.346-0.773], P less than 0.01. A allelic frequency was 20.5% and 11.0% in HCC patients and in control group, respectively, OR was 2.086 (95% CI = 1.191-3.654), P less than 0.01. Gene frequency of RsaI and AluI in the two groups was distributed with polymorphism. CONCLUSION: ERb gene polymorphism is associated with primary liver cancer. R allele may be the guard factor, and A allele may be its risk factor.

Carbapenem-resistant Klebsiella pneumoniae infection causing rupture of graft artery in solid organ recipients: Case report and review of literature.

RATIONALE: Donor-derived bacterial infection is a rare cause of morbidity after solid organ transplantation (SOT) but associated with significant morbidity and mortality, deaths caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) infection account for a considerable proportion of postoperation mortality rate in liver and kidney recipients. The arterial rupture as a result of fungal arteritis is occasionally described, while the rupture of graft vascular anastomosis after SOT due to donor-derived CRKP infection is rarely reported. PATIENTS CONCERNS: We reported 1 patient with donor-derived CRKP infection following liver transplantation and 2 patients following renal transplantation (1 liver and 2 kidneys were from the same donor), who experienced sudden abdominal pain and abdominal hemorrhage almost at the same time after organ transplantation. DIAGNOSIS: The patients were diagnosed as graft arteries rupture due to corrosion caused by CRKP infection based on computed tomography scan, blood culture, laparotomy, and pulse-field gel electrophoresis. INTERVENTIONS: Anti-shock treatment, exploratory laparotomy, broad-spectrum antibiotics, and abdominal puncture and drainage were given. OUTCOMES: The liver recipient survived as well as the liver graft, still under treatment of multiple abdominal infections. The 2 renal recipients were alive after resection of the renal grafts and underwent hemodialysis. LESSONS: Rupture of graft artery should be foreseen when donor-derived CRKP infection was confirmed and broad-spectrum antibiotics and other interventions need to be considered.

An imbalance between stellate cells and γδT cells contributes to hepatocellular carcinoma aggressiveness and recurrence.

PURPOSE: The diagnostic potential of hepatic stellate cells (HSCs) and γδT cells for patients with hepatocellular carcinoma (HCC) and their synergistic contributions to the prognosis of these patients have not yet been investigated. The aim of this study was to elucidate the prognostic value of these cells in HCC. METHODS: The prognostic significance of the ratio of HSCs to γδT cells (SGR) was assessed in a total of 339 HCC patients undergoing resection. The correlation between the circulating tumor cell (CTC) level and SGR in 71 HCC patients was determined using the CellSearch system. In vitro experiments were performed to validate the synergistic effects of HSCs and γδT cells on hepatoma cells. RESULTS: Peritumoral SGR was closely associated with overall survival (OS) and recurrence-free survival (RFS) of HCC patients after resection. In the testing cohort, two nomograms incorporating the SGR were constructed for the prediction of OS and RFS. The predictive accuracy of the two nomograms was verified by the validation cohort. CTC levels were positively correlated with SGR (r = 0.479, p < 0.001). Among the patients with CTCs > 2/7.5 ml, those with a high SGR exhibited higher early recurrence rates than those with a low SGR. In vitro experiments revealed that the secretion of INF-γ, IL-17, and TNF-α from γδT cells was increased after culture with HSC-conditioned medium. In addition, γδT cells cultured with HSC-conditioned medium decreased the proliferative and invasive abilities of hepatoma cells. CONCLUSIONS: The peritumoral SGR is related to aggressive tumor behavior and has a powerful predictive value in HCC. Early recurrence in patients with a high peritumoral SGR might be associated with high CTC levels.

HBV-DNA Load-Related Peritumoral Inflammation and ALBI Scores Predict HBV Associated Hepatocellular Carcinoma Prognosis after Curative Resection.

BACKGROUND: Both persistent inflammatory activity and liver function damage contribute to a poor prognosis of hepatocellular carcinoma (HCC). This study aimed to develop nomograms that incorporate hepatitis virus B (HBV)-related peritumoral inflammation score (PIS) and liver function based on ALBI score to predict postoperative outcomes of HCC. METHODS: The prognostic roles of HBV-related preoperative PIS and ALBI scores in HCC recurrence were examined, and then two nomograms were constructed. The predictive accuracy and discriminative ability of the nomograms were compared with AJCC and BCLC staging systems of HCC. RESULTS: PIS (HBV-PIS) and ALBI scores (HBV-ALBI) with different HBV-DNA loads had association with overall survival (OS) and/or recurrence-free survival (RFS) of HCC. The independent predictors of OS and RFS were incorporated into the corresponding nomograms. In the training cohort, the C-indexes of OS and RFS nomograms were 0.751 and 0.736, respectively. ROC analyses showed that both OS and RFS nomograms had larger AUC (0.775 and 0.739, respectively) than AJCC and BCLC staging systems. These results were verified by the internal and external validation cohorts. CONCLUSION: The proposed nomograms, including HBV-DNA load-related PIS and ALBI scores, were accurate in predicting survival for HCC after curative resection.

Combined Preoperative ALBI and FIB-4 Is Associated with Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy.

BACKGROUND AND PURPOSE: Chronic inflammatory response is a risk factor for hepatocarcinogenesis and recurrence. This study aimed to develop a nomogram incorporating the combined albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) scores and the peritumoral inflammation score (PIS) to predict postoperative recurrence-free survival (RFS) of hepatocellular carcinoma (HCC). METHODS: The prognostic roles of preoperative ALBI and FIB-4 scores for HCC recurrence were investigated, and a nomogram was developed. The predictive ability of the nomogram was compared with the American Joint Commission on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) staging systems for HCC. Necroinflammatory activity in the peritumoral liver tissues was evaluated by hematoxylin and eosin (H&E) staining. RESULTS: Combined ALBI and FIB-4 was associated with PIS in the training and validation cohorts (r = 0.342 and 0.473, both P < 0.001), and all of the scores exhibited predictive value for RFS of HCC. The independent predictive factors of RFS such as AFP, tumor number, tumor size, microvascular invasion, PIS, and combined ALBI and FIB-4 were included in the corresponding nomogram. In the training cohort, the C-index of the RFS nomogram was 0.722. ROC analyses showed that the RFS nomogram had a larger AUC (0.739) than the AJCC and BCLC staging systems. These results were verified by the validation cohort. CONCLUSIONS: The proposed nomogram incorporating PIS and combined ALBI and FIB-4 was associated with recurrence for HCC following curative hepatectomy.

Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy.

In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including α-fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C-indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram-predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.

Expression of stem cell markers CK-19 and PDX-1 mRNA in pancreatic islet samples of different purity from rats.

BACKGROUND: Islet stem cells are more or less retained in the procedure of islet isolation and purification, and are transplanted together with islet grafts. Keratoprotein (CK-19) and pancreatic duodenal hox gene 1 (PDX-1) are markers of stem cells. This study was undertaken to examine the expression of these markers in pancreatic islet samples of different purity from rats. METHODS: A total of 30 male Sprague-Dawley rats were randomly assigned to 3 groups to undergo perfusion with V-type collagenase via the pancreatic duct, then the pancreas was excised, diced, shaken, digested and centrifuged to obtain islet sediments. The sediment from group A was not purified, while that from group B was purified with 25% Ficoll-400 and that from group C with 25% and 11% Ficoll-400. RNA was extracted from the different islet samples for reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of the pancreatic stem cell markers CK-19 and PDX-1 was assessed. RESULTS: The purity of islets in samples was (43.6+/-6.29)% in group A; (65.3+/-4.40)% in group B; and (77.6+/-6.36)% in group C (P<0.05). The expression of CK-19 and PDX-1 mRNA was significantly higher in group A than in groups B and C, but group C showed the lowest level of expression. CONCLUSION: The expression of CK-19 and PDX-1 mRNA in islet samples of different purity suggests the presence of stem cells in all islet samples.