IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer.

OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.

Clinical practice of basin-shaped hepaticojejunostomy following hilar resection of stage III/IV hilar cholangiocarcinoma.

BACKGROUND: Radical surgery for Bismuth type III/IV hilar cholangiocellular carcinoma, which was usually considered unresectable, seems to improve prognosis by increasing the surgical curability rate. However, the dilemma of multiple billiary stumps and high postoperative complication rate caused by hepato-enteric anastomosis has been the main impediment. Thus, we practiced and introduce a new technique called "basin-shaped" hepaticojejunostomy to improve the treatment. METHODS: Thirty-two cases with Bismuth type III/IV hilar cholangiocarcinoma admitted to our department from Aug. 2013 to Dec. 2015 and who underwent hilar resection and resection segment 4(or plus resection segment 1) were reconstructed by "basin-shaped" hepaticojejunostomy. The clinical data were collected and analyzed. RESULTS: All patients underwent successful R0 high hilar resection following basin-shaped hepaticojejunostomy and were discharged from the hospital without severe postoperative complications. The average operation time for hepato-enteric anastomosis was 42.1 ± 8.5 min. The postoperative bile leakage rate was 3.1% (1/32), and the biliary infection rate was 6.2% (2/32). Within a median follow-up of 25.6 months, none of the patients developed local recurrence around the hepato-enteric anastomosis. CONCLUSIONS: For patients with Bismuth type III/IV hilar cholangiocellular carcinoma who underwent resection segment 4(or plus resection segment 1), basin-shaped hepaticojejunostomy was a safe, simple and valid method for bile duct reconstruction, with a relatively low incidence of postoperative complications.

High expression levels of COX-2 and P300 are associated with unfavorable survival in laryngeal squamous cell carcinoma.

In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence (P < 0.05). P300 expression was correlated with COX-2 expression (P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival (P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC.

Adjuvant chemotherapy combined with immunotherapy in patients with cholangiocarcinoma after radical resection.

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.

Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis.

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Effect of tea polyphenol on oxidative injury in S180 cells induced hepatocarcinoma mice.

The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels.

Adjuvant Cytokine-Induced Killer Cell Therapy Improves Disease-Free and Overall Survival in Solitary and Nonmicrovascular Invasive Hepatocellular Carcinoma After Curative Resection.

Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI).In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. Of these, 102 patients received CIK treatment after surgery (CIK group), whereas 205 patients did not (control group). Pathological evaluation was used to retrospectively determine MVI status. The CIK group had 60 MVI-negative and 42 MVI-positive patients, while the numbers in control group were 124 and 81. Kaplan-Meier and Cox regression analyses were used to validate possible effects of CIK treatment on disease free survival (DFS) and overall survival (OS) as appropriate.For all patients, the CIK group exhibited significantly higher OS than the control group (log-rank test; PDFS = 0.055, POS = 0.020). Further analysis based on MVI stratification showed that for patients with MVI, DFS and OS did not differ between the 2 groups (PDFS = 0.439, POS = 0.374). For patients without MVI, the CIK group exhibited better DFS and OS than the control group (PDFS = 0.042, POS = 0.007), and multivariate analyses demonstrated that CIK treatment was an independent prognostic factor both for DFS and OS.For solitary HCC, CIK cell therapy after curative resection improves DFS and OS for patients without MVI, but has no statistically significant survival benefit for patients with MVI.

[The protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion injury and coagulopathy after excision of liver cancer].

OBJECTIVE: To observe the protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion (I/R) injury and coagulopathy in liver cancer patients undergoing excision of hepatic cancer after occlusion of hepatic blood flow. METHODS: A prospective randomly controlled study was conducted. Sixty patients with liver cancer classified as Child-Pugh class A undergoing hepatectomy in the Department of Hepatobiliary Surgery of Sun Yat-sen University Cancer Center from October 2011 to March 2013 were enrolled. The patients were randomized into control group and Xuebijing group (each patient received 100 mL Xuebijing injection added to 0.9% saline as a preoperative treatment for 3 days). Complete blood count, coagulation function, hepatic function, serum pro-inflammatory cytokines and alpha-fetoprotein (AFP) levels were determined before and after operation. RESULTS: Forty-five out of 60 patients were enrolled eventually, with 23 patients in control group and 22 in Xuebijing group, and among them 43 patients were positive for hepatitis B surface antigen (HBsAg) at admission. Compared with those before operation, the postoperative levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) in control and Xuebijing groups were significantly elevated, prothrombin time (PT) and activated partial prothrombin time (AfYIT) were significantly prolonged, and white blood cells (WBC) , proportion of neutrophils (N) and C-reactive protein (CRP) were significantly increased (P<0.05 or P<0.01 ). Although the above indexes in Xuebijing group after operation were lower than those in control group in different degrees [ALT (U/L): 213.1 (80.4-796.6) vs. 265.8 (15.6-882.3), AST (UIL): 194.1 (65.4-914.2) vs. 264.3 (15.4-475.9), LDH (lg,U/L): 5.69 ± 0.72 vs. 5.71 ± 0.72, PT (s): 15.24 ± 2.16 vs. 14.41 ± 1.33, AfYIT (s): 31.51 ± 7.04 vs. 29.47 ± 4.90, WBC (x 109/L) : 13.4 7 ± 4.66 vs. 14.58 ± 4.40, N: 0.87 ± 0.06 vs. 0.87 ± 0.04, CRP (mg/L): 40.64 (16.93-189.59) vs. 45.64 ( 1.65-349.40) J, no statistical significance was found between the groups (all P>0.05 ). The preoperative levels of tumor necrosis factor-a (TNF -a) and interleukin-6 OL-6) were both less than 1.0 ng/L, and the postoperative levels of TNF-a showed no significant change, and IL-6 was increased to 485.10 (104.00-837.50) ng/L and 193.26 (95.10-385.20) ng/L in control and Xuebijing groups respectively (P<0.01). The serum high mobility group box-1 ( HMGB1 ) protein levels after operation were higher than those of preoperative in both groups (both P<0.01), but the postoperative HMGB1 in Xuebijing group were significantly lower than those in control group (j.Lg/L: 268.73 ± 5.56 vs. 277.12 ± 2.92, P<0.01). Acute physiology and chronic health evaluation ll (APACHE ll) score in Xuebijing group was significantly lower than that in control group (4.18 ± 3.75 vs. 4.53 ± 2.34, t=5.328, P=0.027), and the first passage of flatus and defecation after operation in Xuebijing group were significantly earlier than those in control group [exhaust time (days): 3 (2-4) vs. 3 (2-4), U=-2.023, P=0.043; defecation time (days): 4 (2-6) vs. 5 (3-8), U =-2.926, P=0.003 J. However, no difference was found between two groups in the postoperative and total hospital days. Spearman rank correlation analysis showed there were positive correlations between hepatitis B virus (HBV)-DNA levels and preoperative ALT (r=0.414, P=0.044) and AST (r=0.405, P=0.024) in 33 HBV-DNA positive patients, but there was no significant correlation between HBV -DNA levels or other preoperative liver function indicators. CONCLUSIONS: Hepatic I/R injury and coagulopathy may occur in liver cancer patients undergoing resection of cancer with occlusion of hepatic blood flow. Xuebijing injection may inhibit the release of serum pro-inflammatory cytokines, thereby alleviate hepatic I/R injury and promote the recovery of intestinal function. But it does not offer protective effect on coagulopathy.

Clinicopathological characteristics and outcome of primary sarcomatoid carcinoma and carcinosarcoma of the liver.

BACKGROUND: Primary sarcomatoid carcinoma (SC) and carcinosarcoma (CS) of the liver are rare tumors. PATIENTS AND METHODS: From November 1999 to June 2011, clinicopathological features and outcome of 10 SC and 14 CS patients were retrospectively studied. RESULTS: In the SC group, six patients had hepatocellular carcinoma and four had cholangiocellular carcinoma, while in the CS group, it was nine and five patients, respectively. All cases of the sarcomatous components were vimentin-positive. Pan-cytokeratin were stained in sarcomatous components of the SC group, but not in the CS group. The sarcomatous component in the SC group was negative for desmin, myoglobin, HHF35, SMA, CD68, Mac387, AAT, CD34, and S100. In the CS group, the sarcomatous components in six cases were malignant fibrous histiocytomas, six were fibrosarcomas, and two were rhabdomyosarcomas. Median survival times were 9.6 and 4.8 months for the SC and CS groups, respectively (P = 0.483). In univariate analysis, favorable predictors of overall survival were asymptomatic, Child-Pugh class A, no distant metastasis, and radical resection. CONCLUSIONS: SC and CS were highly aggressive malignancies with similar poor survival regardless of the histological and immunohistochemical findings. Early detection through regular physical examination and treatment with radical resection may improve the outcome of those patients.

[Osteopontin as a potential biomarker of metastasis and recurrence for hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Osteopontin (OPN), a secretory phosphorylated glycoprotein and integrin-binding protein, has been involved in tumorigenesis, progression, invasion, and metastasis. OPN is over-expressed in a variety of human tumors. This study was to evaluate the value of OPN detection in forecasting the postoperative metastasis and recurrence of hepatocellular carcinoma (HCC). METHODS: Plasma OPN level of 56 patients with HCC was detected before operation by enzyme-linked immunosorbent assay (ELISA), and plasma samples of 23 healthy volunteers were also analyzed as control group. The correlation of plasma OPN level to metastasis and recurrence of HCC was analyzed. RESULTS: Plasma OPN level was significantly higher in HCC group than in control group [(864.4+/-391.9) microg/L vs. (382.5+/-169.4) microg/L, P<0.001]. During the follow-up, 25 patients had tumor recurred. Plasma OPN level was significantly higher in the patients with early HCC recurrence than in those without recurrence [(961.0+/-411.6) microg/L vs. (744.6+/-323.9) microg/L, P=0.039]. Cox multivariate analysis showed that plasma OPN level, cirrhosis, and tumor size were independent predictors for HCC recurrence and metastasis. CONCLUSION: Plasma OPN level may be a potential diagnostic marker for predicting metastasis and recurrence of HCC.

[Clinical analysis of 38 cases of hepatic focal nodular hyperplasia and literature review].

BACKGROUND & OBJECTIVE: Focal nodular hyperplasia (FNH) is a rare benign hepatic tumor, and its diagnosis and treatment remain controversial. This study was to summarize the clinical features of FNH, and explore its diagnosis and treatment principles. METHODS: Clinical data of 38 FNH patients, treated in our hospital from Jul. 1997 to Jul. 2004, were studied retrospectively with literature review to summarize the clinical feature, diagnosis, and treatment of FNH. All the patients were followed up till Jul. 2004. RESULTS: Among the 38 patients, 30 (78.9%) were under 40 years old, 26 (68.4%) were asymptomatic, 32 (84.2%) had normal liver function, and alpha fetoprotein (AFP) was negative in all the patients. Correct diagnosis rates were 5.3% (2/38) for B ultrasonography, 45.5% (5/11) for color Doppler ultrasound, 100% (2/2) for contrast-enhanced ultrasound, and 36.8% (14/34) for double-phase helical CT scan. Of the 38 patients, 34 (89.5%) underwent hepatic resection without any complication, 1 underwent biopsy and transcatheter arterial embolization (TAE), 2 underwent biopsy and percutaneous ethanol injection (PEI), 1 only underwent biopsy. The size of lesions didn't change after TAE or PEI. HCC appeared in 2 patients with hepatitis 69 and 32 months after the resection of FNH lesions. At the end of follow-up, 37 patients were survival, and the other one died of other disease 1 year after PEI. CONCLUSIONS: The patients with FNH usually have no clinical symptoms with good prognosis. The combination of multiple imaging measures is of help to the diagnosis of FNH. We recommend close observation for patients with confirmed diagnosis of FNH and without clinical symptoms, and recommend surgical resection for those with equivocal diagnosis, symptoms, lesion enlargement, or accompanied with hepatitis or cirrhosis.

[Evaluation of new TNM staging system for hepatocellular carcinoma after hepatectomy].

BACKGROUND & OBJECTIVE: The TNM staging system for hepatocellular carcinoma (HCC) was revised by the International Union Against Cancer (UICC) from the 5th edition (TNM5) to the 6th edition (TNM6) in 2002. This study was to evaluate the prognostic value of TNM6 staging in a large cohort study of HCC patients who underwent hepatectomy, and investigate its feasibility and applicability in China. METHODS: Clinical and follow-up data of 478 HCC patients, who underwent hepatectomy in our center from Jan. 1993 to Dec. 1998, were reviewed retrospectively. Survival rates of the patients were compared according to TNM5 staging and TNM6 staging. The advantages and disadvantages of TNM6 staging were analyzed. RESULTS: According to TNM5 staging, 12 (2.5%) patients were in stage I, 224 (46.8%) in stage II, 95 (19.9%) in stage IIIA, 8 (1.7%) in stage IIIB, and 139 (29.1%) in stage IVA. The 5-year survival rates were 81.8%, 41.5%, 17.0%, 0%, and 10.2%, respectively; there were significant differences in survival rate between stage II and IIIA, between stage II and IIIB, and between stage IIIA and IIIB, but no significant differences were observed between stage I and II, or between stage IIIB and IVA. According to TNM6 staging, 234 (48.9%) patients were in stage I, 41 (8.6%) in stage II, 96 (20.1%) in stage IIIA, 88 (18.4%) in stage IIIB, and 19 (4.0%) in stage IIIC. The 5-year survival rates were 43.3%, 20.2%, 13.1%, 13.0%, and 0, respectively; there was significant difference in survival rate between stage I and II, but no significant differences were found between stage II and IIIA, between stage II and IIIB, and between stage IIIA and IIIB. CONCLUSIONS: TNM6 staging has important improvement, and is simpler than TNM5 staging. But TNM6 staging still has limitation, which is not very accurate to predict the prognosis in clinical practice, and is not suitable for Chinese HCC patients who were usually accompanied with cirrhosis.

[Preliminary study on orthotopic liver transplantation for treatment of advanced hepatocellular carcinoma without extra-hepatic metastasis - a report of 10 cases].

BACKGROUND & OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) are unresectable even without extra-hepatic metastasis. In addition, about 80%-90% patients in China are accompanied with cirrhosis. Liver transplantation is probably more proper for these patients than other treatments. This study was to explore the value of liver transplantation for treatment of advanced HCC without extra-hepatic metastasis, and to summarize the experience of liver transplantation performed in Cancer Center of Sun Yat-sen University. METHODS: Ten patients with advanced HCC without extra-hepatic metastasis who underwent liver transplantation in Sun Yat-sen University Cancer Center from Sept. 2003 to Apr. 2004 were followed up to May 2004, and their clinical records were reviewed retrospectively. RESULTS: The mortality within 1 month after operation was 0.0% for 10 cases of liver transplantation. One patient was alive for 7 month with tumor recurrence, and the remaining 9 patients were alive for 1-6 months without recurrence. Alpha fetoprotein (AFP) decreased to normal range within 2 months in 2 cases with macro tumor thrombus in the trunk of portal vein, and the left branch of portal vein, respectively. CONCLUSION: Advanced HCC without extra-hepatic metastasis, even with macro tumor thrombus in portal vein, is still indicated for liver transplantation.