Toripalimab in combination with Anlotinib for unresectable hepatocellular carcinoma after SBRT: A prospective, single-arm, single-center clinical study.

Objective: Exposing tumor antigens to the immune system is the key to ensuring the efficacy of immunotherapy. SBRT is the main way to reveal the specifical antigens of tumors which can enhance the immune response. We aimed to explore the clinical efficacy and safety of Toripalimab combined with Anlotinib for uHCC after SBRT. Methods: This is a prospective, single-arm, explorative clinical study. uHCC patients with an ECOG PS score of 0-1, Child-Pugh class A or B, and BCLC stage B or C were included and treated with SBRT(8Gy*3) followed by 6-cycle combinational therapy with Toripalimab and Anlotinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of treatment-related adverse events (TRAEs). Continuous variables were presented as medians and ranges. Survivals were studied with the Kaplan-Meier method. Categorical data were expressed as n (percentage). Results: Between June 2020 and October 2022, a total of 20 patients with intermediate-advanced uHCC were enrolled. All cases had multiple intrahepatic metastases, or macrovascular invasion, or both, among whom 5 cases with lymph node or distant metastases. Until September 2022, the median follow-up time was 7.2 months (range, 1.1-27.7 months). Median survival time could not be assessed at the moment, based on iRecist, median PFS was 7.4 months (range, 1.1-27.7 months), ORR 15.0%, and DCR 50.0%. 14 patients experienced treatment-related adverse events with an incidence of 70%. The overall survival rates at 18 months and 24 months were 61.1% and 50.9%, respectively. And the progression-free survival rates were 39.3% and 19.7%. Conclusion: Exposure of specific antigens of HCC via SBRT may improve the efficacy of combinational therapy with Toripalimab and Anlotinib for uHCC with manageable adverse effects, which deserves further exploration. Clinical trial registration: www.clinicaltrials.gov, identifier ChiCTR2000032533.

Orthotopic liver transplantation improves postoperative quality of life, survival rate and reduces recurrence rate in patients with liver cancer.

OBJECTIVE: To evaluate the impact of orthotopic liver transplantation (OLT) on postoperative quality of life (QoL), survival rate and recurrence rate of patients with liver cancer (LC). METHODS: One hundred and twenty-seven patients with LC treated in our hospital from December 2016 to January 2018 were divided into two groups according to different treatment schemes. Patients in the research group (n=67) were given OLT and those in the control group (n=60 cases) were given hepatectomy. The incidence of postoperative complications, hospitalization expenses, the time to liver function recovery, surgical wound healing, pain resolution and hospitalization were compared between the two groups. The overall survival rate (OSR), disease-free survival rate (DFSR), and average survival time of patients were recorded and compared. The Visual Analogue Scale (VAS) score one day and three days after surgery, alpha-fetoprotein (AFP) level, and adverse emotion before and after operation were compared. QoL scores at six months after surgery, one-year recurrence and metastasis rates, and treatment satisfaction one year after surgery were also compared. The expression of Ki-67 and Topo IIαin the tumor-bearing group (n=5) was detected. RESULTS: The research group presented markedly lower incidence of postoperative complications, and evidently shorter time to liver function recovery, surgical wound healing, pain resolution and hospitalization, while with noticeably higher hospitalization expenses. The one-year and five-year OSRs and DFSRs were noticeably higher, and the average survival time was remarkably longer in the research group as compared to the control group. Patients in the research group scored remarkably lower in VAS scores on the first and third day after surgery than patients in the control group. In comparison with the control group, the one-year recurrence and metastasis rates were evidently lower in the research group, and the scores of SF-36 were remarkably higher. The AFP level at one month after surgery was obviously lower in the research group, and the treatment satisfaction was greatly higher. Ki-67 in the tumor-bearing group was mainly located in the nucleus, and Topo IIα was mainly nucleus positive; the positive Ki-67 and Topo IIα expression rates in the tumor-bearing group was 66.7% and 69.8%, respectively. CONCLUSIONS: OLT can improve the postoperative QoL, survival rate and reduce the recurrence rate of LC patients.

Prediction of post-hepatectomy liver failure and long-term prognosis after curative resection of hepatocellular carcinoma using liver stiffness measurement.

BACKGROUND AND STUDY AIMS: Post-hepatectomy liver failure (PHLF) is the main cause of perioperative death after hepatocellular carcinoma (HCC) resection. PHLF occurrence is related to both the hepatectomy volume and the degree of cirrhosis. Accurate preoperative assessment of the degree of cirrhosis may aid in reducing the incidence of PHLF. Several studies have shown that the liver stiffness measurement (LSM) is well correlated with cirrhosis. This study explored the relationship between LSM and PHLF occurrence after radical HCC resection and the effect on long-term prognosis. PATIENTS AND METHODS: We retrospectively analyzed the clinical data of 164 patients who underwent radical HCC resection at our center from January 2017 to January 2020. The related postoperative PHLF factors were analyzed. The LSM threshold in postoperative PHLF was calculated through receiver operating characteristic (ROC) curve analysis. Patients were grouped according to different LSM thresholds and survival analysis was performed. RESULTS: Forty-six patients experienced PHLF, of whom 19, 21, and 6 were classified as grades A, B, and C, respectively. Multivariate analysis indicated that LSM was an independent risk factor for PHLF after HCC surgery (OR = 1.174, P < 0.000). LSM (OR = 1.219, P < 0.000) and intraoperative bleeding (OR = 1.001, P = 0.047) were risk factors for grade B-C PHLF. The LSM threshold that predicted PHLF occurrence was 17.9 kPa (AUC = 0.831, P < 0.000) and 24.5 kPa (AUC = 0.867, P < 0.000) for grade B-C PHLF. LSM was correlated with PHLF severity (r = 0.439, P < 0.001). The median survival times were 32 vs 26 months (P = 0.016) for patients with LSM ≤ 17.9 kPa vs those with LSM > 17.9 kPa and 28 vs 24 months (P = 0.004) for patients with LSM ≤ 24.5 kPa vs those with LSM > 24.5 kPa. CONCLUSION: LSM is related to PHLF occurrence in patients undergoing HCC resection; a higher LSM is associated with the occurrence of more severe PHLF after surgery. In addition, LSM may aid in predicting long-term survival after liver resection in patients with HCC.

Efficacy and safety of transarterial chemoembolization plus sorafenib in patients with recurrent hepatocellular carcinoma after liver transplantation.

Objectives: To explore the benefit and safety of transarterial chemoembolization (TACE) in combination with sorafenib in patients with recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). Methods: In this multi-center retrospective study, 106 patients with recurrent HCC after OLT were included. Fifty-two patients were treated with TACE plus sorafenib (TS group) and 54 were treated with TACE alone (TC group). Primary and secondary endpoints including overall survival (OS) and progression-free survival (PFS), and safety were assessed. Results: The median OS (17 vs 10 months, P=0.035) and PFS (12 vs 6 months, P=0.004) in the TS group were longer than those in the TC group. On multivariate analysis, BCLC stage (HR [hazard ratio]=0.73 [95% CI, 0.27-0.99], P=0.036) and sorafenib medication (HR=2.26 [95% CI, 1.35-3.69], P=0.01) were identified as independent prognostic risk factors for OS. No severe adverse events related to sorafenib were noted in the TS group. Four patients discontinued sorafenib due to intolerance. Conclusion: TACE in combination with sorafenib is a feasible regimen to improve the survival with mild toxicity in patients with recurrent HCC after OLT.

Correlationship between Ki67, VEGF, and p53 and Hepatocellular Carcinoma Recurrence in Liver Transplant Patients.

BACKGROUND AND AIMS: Patients with hepatocellular carcinoma (HCC) who undergo orthotopic liver transplantation (OLT) are at risk for posttransplant tumor recurrence. The aim of this study was to evaluate the correlation between the expression of Ki67, VEGF, and p53 in HCC and clinicopathological characteristics of HCC patients, as well as their predictive value for HCC recurrence after OLT. METHODS: 60 patients who underwent OLT and were found to have HCC in the liver explant. The expression of Ki67, VEGF, and p53 in HCC was detected by immunohistochemistry. RESULTS: Ki67 was associated with the tumor number and the grade of differentiation at baseline. VEGF was associated with the diameter and number of tumors, tumor differentiation, and lymph node metastasis. p53 was associated with the tumor diameter and tumor encapsulation. The expression of Ki67, VEGF, and p53 in HCC was correlated with the tumor recurrence after OLT, respectively. Among them, VEGF was an independent predictor for tumor recurrence after OLT. CONCLUSION: Ki67, VEGF, and p53 are associated with the recurrence of HCC after OLT. VEGF independently predicts the recurrence of HCC.

Impact of iatrogenic biliary injury during laparoscopic cholecystectomy on surgeon's mental distress: a nationwide survey from China.

BACKGROUND: Iatrogenic biliary injury (IBI) following laparoscopic cholecystectomy (LC) is the most serious iatrogenic complications. Little is known whether LC-IBI would lead to surgeon's severe mental distress (SMD). METHODS: A cross-sectional survey in the form of electronic questionnaire was conducted among Chinese general surgeons who have caused LC-IBI. The six collected clinical features relating to mental distress included: 1) feeling burnout, anxiety, or depression, 2) avoiding performing LC, 3) having physical reactions when recalling the incidence, 4) having the urge to quit surgery, 5) taking psychiatric medications, and 6) seeking professional psychological counseling. Univariable and multivariable analyses were performed to identify risk factors of SMD, which was defined as meeting ≥3 of the above-mentioned clinical features. RESULTS: Among 1466 surveyed surgeons, 1236 (84.3%) experienced mental distress following LC-IBI, and nearly half (49.7%, 614/1236) had SMD. Multivariable analyses demonstrated that surgeons from non-university affiliated hospitals (OR:1.873), patients who required multiple repair operations (OR:4.075), patients who required hepaticojejunostomy/partial hepatectomy (OR:1.859), existing lawsuit litigation (OR:10.491), existing violent doctor-patient conflicts (OR:4.995), needing surgeons' personal compensation (OR:2.531), and additional administrative punishment by hospitals (OR:2.324) were independent risk factors of surgeon's SMD. CONCLUSION: Four out of five surgeons experienced mental distress following LC-IBI, and nearly half had SMD. Several independent risk factors of SMD were identified, which could help to make strategies to improve surgeons' mental well-being.

Comparison of Regorafenib, Fruquintinib, and TAS-102 in Previously Treated Patients with Metastatic Colorectal Cancer: A Systematic Review and Network Meta-Analysis of Five Clinical Trials.

BACKGROUND This study aimed to conduct a systematic review of the literature to identify key randomized controlled clinical trials (RCTs), followed by network meta-analysis, to compare the efficacy and safety profiles of regorafenib, fruquintinib, and TAS-102 in previously treated patients with metastatic colorectal carcinoma (mCRC). MATERIAL AND METHODS Systematic literature review was performed using the Medline, Embase, and Cochrane library online databases to identify published randomized controlled trials (RCTs). Hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and the odds ratios (ORs) for the objective response rate (ORR), disease control rate (DCR), adverse events (AEs), serious adverse events (SAEs), and fatal adverse events (FAEs) were compared indirectly using network meta-analysis based on a random-effects model. RESULTS Five RCTs that included 2,604 patients fulfilled the eligibility criteria and were analyzed. Indirect comparisons showed that fruquintinib was associated with significant superiority for PFS (HR, 0.57; 95% CI, 0.34-0.95) and DCR (OR, 1.80; 95% CI, 1.08-3.01) when compared with TAS-102 in patients with mCRC. However, there was no significant difference between OS or ORR between regorafenib, fruquintinib, and TAS-102. Fruquintinib was associated with a significantly higher risk of SAEs when compared with TAS-102 or regorafenib. There was no significant difference in the risk of AEs or FAEs following indirect comparison between fruquintinib, regorafenib, and TAS-102. CONCLUSIONS The findings from network meta-analysis showed that fruquintinib was associated with significant superiority for PFS and DCR compared with TAS-102, but fruquintinib was associated with significantly increased risk for SAEs compared with regorafenib and TAS-102.

Expression of miR-664-3p in Osteosarcoma and Its Effects on the Proliferation and Apoptosis of Osteosarcoma Cells.

BACKGROUND: To explore the expression level of miR-664-3p in osteosarcoma and its effects on the proliferation and apoptosis of osteosarcoma cells. METHODS: Specimens of osteosarcoma tissues were collected from 41 cases undergoing surgical treatment in the Orthopedics Department of Wuhan Puai Hospital, Wuhan, China from January 2015 to February 2018. Another 40 cases of normal bone tissue were collected. The expression of miR-664-3p were detected using quantificational real-time polymerase chain reaction. miR-664-3p mimics, miR-664-3p inhibitor and miR-664-3p negative control (NC) were used to transfect U2-OS, which were named as mimics group, inhibitor group and NC group, respectively. MTT assay was adopted to detect the effects of microRNA-664-3p on the proliferation of U2-OS after 24, 48, 72, 96 and 120 hours of transfection. Flow cytometry was applied to measure the apoptosis rate of U2-OS after miR-664-3p transfection. Finally, Western Blot was employed to detect the expression of proteolipid protein 2 (PLP2). RESULTS: The total apoptosis rate of cells in the inhibitor group was obviously higher than those in the mimics group and the NC group (P<0.001). The relative expression level of PLP2 in the inhibitor group was significantly lower than those in the mimics group and the NC group (P<0.001). CONCLUSION: MiR-664-3p may be involved in the occurrence and development of osteosarcoma, and can regulate the proliferation and apoptosis of U2-OS cells, and the expression of PLP2. Besides, miR-664-3p may become a novel molecular biological indicator for the diagnosis, targeted treatment and prognosis assessment of osteosarcoma.

Valproic acid exhibits anti-tumor activity selectively against EGFR/ErbB2/ErbB3-coexpressing pancreatic cancer via induction of ErbB family members-targeting microRNAs.

BACKGROUND: Deregulated ErbB signaling plays an important role in tumorigenesis of pancreatic cancer. However, patients with pancreatic cancer benefit little from current existed therapies targeting the ErbB signaling. Here, we explore the potential anti-tumor activity of Valproic acid against pancreatic cancer via targeting ErbB family members. METHODS: Cell viability assay and apoptosis evaluation were carried out to determine the efficacy of VPA on pancreatic cancer cells. Western blot analyses were performed to determine the expression and activation of proteins. Apoptosis enzyme-linked immunosorbent assay was used to quantify cytoplasmic histone associated DNA fragments. Lentiviral expression system was used to introduce overexpression of exogeneous genes or gene-targeting short hairpin RNAs (shRNAs). qRT-PCR was carried out to analyze the mRNAs and miRNAs expression levels. Tumor xenograft model was established to evaluate the in vivo anti-pancreatic cancer activity of VPA. RESULTS: VPA preferentially inhibited cell proliferation/survival of, and induced apoptosis in EGFR/ErbB2/ErbB3-coexpressing pancreatic cancer cells within its clinically achievable range [40~100 mg/L (0.24~0.6 mmol/L)]. Mechanistic investigations revealed that VPA treatment resulted in simultaneous significant down-regulation of EGFR, ErbB2, and ErbB3 in pancreatic cancer cells likely via induction of ErbB family members-targeting microRNAs. Moreover, the anti-pancreatic cancer activity of VPA was further validated in tumor xenograft model. CONCLUSIONS: Our data strongly suggest that VPA may be added to the treatment regimens for pancreatic cancer patients with co-overexpression of the ErbB family members.

Fecal fusobacterium nucleatum for detecting colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the efficacy of fecal Fusobacterium nucleatum ( Fn) for detecting colorectal cancer. It is the first systematic review and meta-analysis to focus exclusively on fecal Fn for colorectal cancer. MATERIALS AND METHODS: Comprehensive searches of several databases before January 2018 were conducted. Fecal Fn for detecting colorectal cancer was evaluated via pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve. Heterogeneity was explored using meta-regression and subgroup analyses. The publication bias and the overall quality of evidence were also analyzed. RESULTS: Our analysis included six papers containing seven case-control studies in the systematic review and meta-analysis. Overall sensitivity and specificity were 0.68 (95% confidence interval (CI) 0.64, 0.72) and 0.78 (95% CI 0.75, 0.81), respectively. The positive likelihood ratio and negative likelihood ratio in detecting colorectal cancer were 2.87 (95% CI 1.62, 5.10) and 0.40 (95% CI 0.30, 0.54) respectively. The diagnostic odds ratio (OR) was 8.75 (95% CI 4.86, 15.78) and the area under the curve was 0.80. A subgroup analysis showed that in Asia, the colorectal cancer sample size ⩾50 had higher specificity (specificity 0.85, 95% CI 0.80, 0.88). No publication bias existed. The GRADEpro showed a moderate level of the available evidence. CONCLUSIONS: Compared to other examinations, the fecal Fn test seems a good choice for detecting colorectal cancer. It also has better diagnostic performance in Asians. However, more clinical trials with large sample sizes and strict randomization are needed to further verify the evidence.

Influence of UGT1A1 gene methylation level in colorectal cancer cells on the sensitivity of the chemotherapy drug CPT-11.

OBJECTIVE: To study the influence of the methylation level of UGT1A1 gene related to CPT-11 metabolic enzymes in colorectal cancer cells on the sensitivity of chemotherapy drugs. METHODS: Test the changes in sensitivity of seven colorectal cancer cell strains that have been/not been subject to DAC treatment to CPT-11, analyze its correlation with CES2, UGT1A1 and GUSB mRNA expression according to IC50; screen the effective interference sequence of UGT1A1 siRNA, test the changes in cytotoxicity of CPT-11 after UGT1A1 siRNA is transfected, select RK0 cells and make them transfected with the chemosynthetic UGT1A1 siRNA after their UGT1A1 expression is restored with or without demethylation treatment. RESULTS: The sensitivity of different colorectal cancer cell strains to CPT-11 showed difference (P<0.05), UGT1A1 expression in colorectal cell lines had a negative correlation with the IC50 (r=0.790648, P<0.05), the interference efficiency of the screened UGT1A1 siRNA was up to 78%. The IC50 value of siRNA decreased by nearly one time after transfected with HT-29 (P<0.01); which of methylated RK0 cells of UGT1A1 gene increased instead after the demethylation treatment. However, the IC50 value of the demethylation treatment group increased compared with the non-demethylation treatment group after UGT1A1 siRNA was transfected. CONCLUSIONS: The cytotoxicity of CPT-11 to colorectal cancer cells has a negative correlation with UGT1A1 expression, and positive correlation with CES2 and GUSB. The specific silencing UGT1A1 gene of siRNA could significantly increase the sensitivity of CPT-11 to the chemotherapy of colorectal cancer cells. UGT1A1 methylation was an important factor affecting the chemosensitivity of CPT-11.

HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-glycoprotein.

BACKGROUND: Multidrug resistance (MDR) is one of the major reasons chemotherapy-based treatments fail. Hypoxia is generally associated with tumor chemoresistance. However, the correlation between the heterodimeric hypoxia-inducible factor-1 (HIF-1) and the multidrug resistance (MDR1) gene/transporter P-glycoprotein (P-gp) remains unclear. This study aims to explore the molecular mechanisms of reversing colon cancer MDR by focusing on the target gene HIF-1α. METHODS: A chemotherapeutic sensitivity assay was used to observe the efficiency of MDR reversal in LoVo multicellular spheroids (MCS). The apoptotic level induced by different drugs was examined by flow cytometry (FCM). Binding of HIF-1α to the MDR1 gene promoter was evaluated by Chromatin immunoprecipitation (ChIP). The relationship between HIF-1α/P-gp expression and sensitivity to chemotherapy was analyzed. RESULTS: The sensitivity of LoVo MCS to all four chemotherapy drugs was decreased to varying degrees under hypoxic conditions. After silencing the HIF-1α gene, the sensitivities of LoVo MCS to all four chemotherapy drugs were restored. The apoptotic levels that all the drugs induced were all decreased to various extents in the hypoxic group. After silencing HIF-1α, the apoptosis level induced by all four chemotherapy drugs increased. The expression of HIF-1α and P-gp was significantly enhanced in LoVo MCS after treatment with hypoxia. Inhibiting HIF-1α significantly decreased the expression of MDR1/P-gp mRNA or protein in both the LoVo monolayers and LoVo MCS. The ChIP assay showed that HIF-1α was bound to the MDR1 gene promoter. Advanced colon carcinoma patients with expression of both HIF-1α and P-gp were more resistant to chemotherapy than that with non expression. CONCLUSIONS: HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-gp. The expression of HIF-1α and MDR1/P-gp can be used as a predictive marker for chemotherapy resistance in colon cancer.

Overexpression of microRNA-122 re-sensitizes 5-FU-resistant colon cancer cells to 5-FU through the inhibition of PKM2 in vitro and in vivo.

5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in the treatment of colon cancer. However, acquired chemoresistance is becoming one of the major challenges for patients with advanced stages of colon cancer. Currently, the mechanisms underlying cancer cell resistance to 5-FU are not fully understood. MicroRNAs (miRNA) have been suggested to play important roles in tumorigenesis and drug resistance in colon cancer. In this study, we generated 5-FU-resistant colon cancer cell lines from which we found that miR-122 was downregulated in 5-FU-resistant cells compared with sensitive cells. Meanwhile, the glucose metabolism is significantly upregulated in 5-FU-resistant cells. We report that PKM2 is a direct target of miR-122 in colon cancer cell. Importantly, overexpression of miR-122 in 5-FU-resistant cells resensitizes 5-FU resistance through the inhibition of PKM2 both in vitro and in vivo. In summary, these findings reveal that the dysregulated glucose metabolism contributes to 5-FU resistance, and glycolysis inhibition by miR-122 might be a promising therapeutic strategy to overcome 5-FU resistance.

Regulation and expression of aberrant methylation on irinotecan metabolic genes CES2, UGT1A1 and GUSB in the in-vitro cultured colorectal cancer cells.

OBJECTIVE: To evaluate the aberrant methylation gene expression related to the irinotecan (CPT-11) metabolic enzymes in different colorectal cancer cell strains; provide new thoughts and measures for reverse of tumor drug resistance. METHODS: Studied the aberrant methylation state of CES2, UGT1A1 and GUSB in eight colorectal cancer cell strains through MSP method; and analyze the expression of the target gene after being dealt with DAC. RESULTS: UGT1A1 showed methylation in five cell strains, while CES2 and GUSB respectively showed consistent unmethylation or hemimethylation. After being dealt with DAC, CES2 and GUSB mRNA showed different expressions but not significant. The expression quantity of UGT1A1mRNA in the low-expression cell strains increased significantly. The expression of UGT1A1 protein where POSITIVE presented low expression was up-regulated to different degrees. Negative tropism was found in CES2 and UGT1A1. CONCLUSION: Methylation in UGT1A1 gene expression silencing as an important mechanism; methylation could provide an effective target for methylation regulation intervening in the treatment of CPT-11. Meanwhile, studies found that the changes in expressions of CES2 and GUSB might be resulted from some unknown target that still existed during the regulation, or from the influence of methylation in the non-core zone of promoters on the gene transcription.

Expression of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa co-determines the prognosis of colon cancer patients.

Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto-oncogene that is linked to the development and progression of several cancers. In this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor-adjacent mucosa together as an independent prognostic factor for colon cancer patients. The study included 343 colon cancer patients. Immunohistochemical staining was used to detect pim-1. Multivariate cox regression for disease-free survival (DFS) were used to identify independent prognostic factors. Analytic hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score (PTS) for recurrence and survival. Kaplan-Meier DFS curves and OS curves for patients with different pim-1 expression levels were compared using the log-rank test. In this study, four independent prognostic factors were identified for colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent mucosa, as well as tumor stage. It has been established that clinical stage is an important prognostic factor for colon cancer patients. However, PTS can identify the patients who are likely to recur not only in the whole radical excision group but also within each stage of this group. Based on the results of this study we can conclude that the PTS combined with clinical staging system may be a better predictor of colon cancer patients' prognosis than using the clinical stage system alone. ClinicalTrials.gov Number: ChiCTR-PRCH-12002842.

[Treatment of the ununited lower limb fracture with reamed intramedullary interlocking nail].

OBJECTIVE: To investigate the clinical effect of the treatment of the ununited lower limb fracture with reamed intramedullary interlocking nail. METHODS: Fifty-two patients with ununited lower limb fracture were treated with intramedullary interlocking nail (femur 36, tibia 16). The main cause of nonunion was interternal fixation loosening or fracture (41 cases, 78.8%), other reasons included bone defection, bone infection or too much traction of fracture (11 cases, 21.2%). According to X-ray classification: 41 cases in type hypertrophy, 11 cases in type atrophy. All these patients need operation to remove the primary implant, clean the hard bone, ischemia bone and scar, manual ream and fix by intramedullary interlocking nail, then bone graft were done around the fracture site. With the knee joint stiffness, relax it by manipulate or operation. RESULTS: Beside 3 superficial infection (2 delayed healing and 1 healing after debridement), other 49 wounds healed on time. All cases were followed up for an average of 25.2 months, ranging from 12 months to 39 months. All the ununion healed from 5 to 11 months, mean union time were 6.1 months. Deep tissue infection, fat embolism, implant loosening, nail broken or nonunion were not found in this series. According to judet standard on the movement of knee, the excellent-good rate was 82.7%. CONCLUSIONS: Intramedullary interlocking nail is effective to treat nonunion of lower limb fracture.

[VPC regimen combined with whole-brain radiotherapy in the treatment of small cell lung cancer with brain metastasis].

BACKGROUND: The main treatment strategy of cancer patients with brain meta- stasis is irradiation, while so far there is few research concerning chemotherapy combined with radiotherapy for these patients. The aim of this study is to evaluate the therapeutic effect and toxicity of chemotherapy with VPC regimen combined with whole-brain radiotherapy (WBRT) in small cell lung cancer (SCLC) with brain metastasis. METHODS: A total of 60 SCLC patients with brain metastasis received a cycle of VPC regimen (teniposide 60mg/m² iv on days 1-5, cisplatin 35mg/m² iv on days 1-3, semustine 80mg/m² PO on day 1) every 3-4 weeks. WBRT was administered on day 6 of the first cycle of chemotherapy at a dose of 2Gy given in 5 fractions per week. Patients with less than 3 brain lesions received WBRT at a dose of 30Gy and then small field radiotherapy up to total dose of 50Gy, otherwise they received WBRT at a total dose of 40Gy. Response was evaluated by brain and chest CT or MRI after WBRT and at least 2 cycles of chemotherapy were completed. RESULTS: All the patients completed WBRT combined with chemotherapy. Total response rate of primary pulmonary tumor was 46.7%, with 4 cases of CR. The objective brain response rate was 60.0%, with 11 cases of CR and 25 cases of PR. Symptom relief was observed in all 48 patients with neurological symptoms. Main adverse effects were myelotoxicity, nausea/vomiting, constipation and alopecia. The follow-up rate was 93.3% with a median survival duration of 11.3 months. The 1-, 2- and 5-year survival rate was 43.3%, 35.0% and 6.7%, respectively. CONCLUSIONS: Chemotherapy combined with WBRT can be safely performed for SCLC with brain metastasis and its short-term response is quite satisfactory. It may be worthy of further clinical investigation.

[Exploratory study on related factors of sexual dysfunction among breast cancer patients].

OBJECTIVE: To investigate the factors related to sexual dysfunction among breast cancer patients so as to improve the prevention and treatment of the disorder as well as the life quality of the patients. METHODS: Sixty-five breast cancer patients during the rehabilitation period were interviewed by questionnaire on the sexual function before and after treatment. RESULTS: Age and perception of sex were two important factors for the significant difference in the rate of sexual dysfunction among the patients. In the groups of 45-55 and 56-65 years, the rates of sexual dysfunction were 66.7% and 73.9%, respectively. Compared with the < 45-year group (33.3%), the findings were statistically significant (P < 0.01), and the difference was statistically significant between the incorrect perception group (70.3%) and the correct one (47.6%) (P < 0.05). Of all the factors analyzed in the research, the stage of cancer, treatment methods, vaginal dryness, decreased libido, dyspareunia and sex perception had significant correlation with newly developed sexual dysfunction (P < 0.05). CONCLUSION: The stage of cancer, treatment methods, sex perception, vaginal dryness et al had significant correlation with sexual dysfunction of breast cancer patients after treatment. To treat and prevent sexual dysfunction among breast cancer patients, oncology professionals should initiate communication about sexual difficulties, perform comprehensive assessments, and educate and counsel patients about the management of these difficulties.

[Treatment of fracture of neck of femur in the aged with hollow compression screw].

OBJECTIVE: To summarize the clinical results of hollow compression screw in treatment of fracture of neck of femur in the aged. METHODS: From November 1993 to October, 1998, 52 aged patients with several types of fracture of neck of femur were treated; among them, there were 25 males and 27 females aged from 60 to 83 years (70 years on average). There were 48 cases of fresh fracture and 4 cases of old fracture. Forty-two cases were performed closed reduction internal fixation, 10 cases with open reduction internal fixation. RESULTS: All the patients could sit by themselves 4 to 6 days after operation, and could walk with a crutch 10 to 15 days after operation. The mobility of hip joint was nearly normal 4 weeks after operation. All the patients were followed 26 to 84 months, 48.5 months on average. Bone union was achieved in 50 cases, nonunion in 2 cases. The average healing time was 4.7 months. There were no other complications, such as ankylosis and muscular atrophy, but ischemic necrosis in 3 cases. CONCLUSION: This method has following advantages, convenient manipulation, less injury, stable fixation, and the short-term recovery, which avoid some common complications. It is a reliable method worthy of popularizing.