Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Oral chemotherapy versus observation alone in nasopharyngeal carcinoma patients with persistently detected circulating cell-free Epstein-Barr virus DNA during follow-up.

AIM: Despite the high risk of tumor recurrence, patients with nasopharyngeal carcinoma (NPC) with persistently (at least twice) detected circulating cell-free Epstein-Barr virus (EBV) DNA levels during follow-up are routinely recommended to keep observation. For these patients, whether administering more aggressive treatment could improve survival outcomes remains unknown. MATERIALS AND METHODS: We retrospectively included 431 patients with nonmetastatic NPC with persistently detected EBV DNA during follow-up, who do not have clinical or imaging evidence of recurrence. Among these patients, 79 were administered oral chemotherapy, and the remaining 352 underwent observation alone. Baseline characteristics were balanced with propensity score matching (PSM) analysis. The primary endpoint was modified disease-free survival (mDFS), defined as time from detectable EBV DNA result to tumor recurrence or death. The secondary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: One-to-three PSM resulted in 251 eligible patients (oral chemotherapy group, 73; observation group, 178). In the matched cohort, the oral chemotherapy group had higher median mDFS (12.9 months [95 % confidence interval [CI] 9.6-16.3] vs. 6.8 months [95 % CI 5.8-7.8], p = 0.009) and DFS (24.1 months [95 % CI 18.5-29.7] vs. 16.7 months [95 % CI 14.4-19.1], p = 0.035) than the observation group. The median OS was numerically higher in the oral chemotherapy group than in the observation group (57.9 months [95 % CI 42.5-73.3] vs. 50.8 months [95 % CI 39.7-61.9], p = 0.71). A consistent benefit favoring oral chemotherapy was observed for mDFS in all subgroups analyses for male, <45 years, stage III-IVa disease, pretreatment EBV DNA load ≥ 4,000 copies/mL, no induction chemotherapy, or a detectable EBV DNA load ≥ 1,200 copies/mL. After adjusting for other confounders in the multivariate analysis, oral chemotherapy remained a significantly favorable factor for both mDFS (hazard ratio [HR] 0.67, 95 % CI 0.50-0.89; p = 0.006) and DFS (HR 0.68, 95 % CI 0.51-0.91; p = 0.01), but not a significant factor for OS (HR 0.89, 95 % CI 0.62-1.27; p = 0.52). CONCLUSIONS: In patients with NPC having persistently detected EBV DNA levels but without clinical or imaging evidence of recurrence during follow-up, oral chemotherapy significantly prolongs mDFS and DFS. Employing oral chemotherapy as a more aggressive treatment option, as opposed to mere observation, could potentially benefit these patients, although further prospective validation is necessitated.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

SZT2 variants associated with partial epilepsy or epileptic encephalopathy and the genotype-phenotype correlation.

Background: Recessive SZT2 variants are reported to be associated with developmental and epileptic encephalopathy 18 (DEE-18) and occasionally neurodevelopment abnormalities (NDD) without seizures. This study aims to explore the phenotypic spectrum of SZT2 and the genotype-phenotype correlation. Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported SZT2 mutations were systematically reviewed to analyze the genotype-phenotype correlations. Results: SZT2 variants were identified in six unrelated cases with heterogeneous epilepsy, including one de novo null variant and five pairs of biallelic variants. These variants had no or low frequencies in controls. All missense variants were predicted to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients with null variants exhibited DEE. The patients with biallelic null mutations presented severe DEE featured by frequent spasms/tonic seizures and diffuse cortical dysplasia/periventricular nodular heterotopia. The three patients with biallelic missense variants presented mild partial epilepsy with favorable outcomes. Analysis of previously reported cases revealed that patients with biallelic null mutations presented significantly higher frequency of refractory seizures and earlier onset age of seizure than those with biallelic non-null mutations or with biallelic mutations containing one null variant. Significance: This study suggested that SZT2 variants were potentially associated with partial epilepsy with favorable outcomes without NDD, expanding the phenotypic spectrum of SZT2. The genotype-phenotype correlation helps in understanding the underlying mechanism of phenotypic variation.

Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial.

OBJECTIVES: To address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma. DESIGN: Open-label, non-inferiority, multicentre, randomised, phase 3 trial. SETTING: Three Chinese hospitals between 20 November 2017 and 3 December 2018. PARTICIPANTS: Adults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement. INTERVENTIONS: Randomisation was done centrally by the Clinical Trials Centre at Sun Yat-sen University Cancer Center. Eligible patients were randomly assigned (1:1; block size of four) to receive MRLN sparing radiotherapy or standard radiotherapy (both medial and lateral retropharyngeal lymph node groups), and stratified by institution and treatment modality as follows: radiotherapy alone; concurrent chemoradiotherapy; induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy. MAIN OUTCOME MEASURES: Non-inferiority was met if the lower limit of the one sided 97.5% confidence interval of the absolute difference in three year local relapse-free survival (MRLN sparing radiotherapy minus standard radiotherapy) was greater than -8%. RESULTS: 568 patients were recruited: 285 in the MRLN sparing radiotherapy group; 283 in the standard radiotherapy group. Median follow-up was 42 months (interquartile range 39-45), intention-to-treat analysis showed that the three year local relapse-free survival of the MRLN sparing radiotherapy group was non-inferior to that of the standard radiotherapy group (95.3% v 95.5%, stratified hazard ratio 1.04 (95% confidence interval 0.51 to 2.12), P=0.95) with a difference of -0.2% ((one sided 97.5% confidence interval -3.6 to ∞), Pnon-inferiority<0.001). In the safety set (n=564), the sparing group had a lower incidence of grade ≥1 acute dysphagia (25.5% v 35.1%, P=0.01) and late dysphagia (24.0% v 34.3%, P=0.008). Patient reported outcomes at three years after MRLN sparing radiotherapy were better in multiple domains after adjusting for the baseline values: global health status (mean difference -5.6 (95% confidence interval -9.1 to -2.0), P=0.002), role functioning (-5.5 (-7.4 to -3.6), P<0.001), social functioning (-6.2 (-8.9 to -3.6), P<0.001), fatigue (7.9 (4.0 to 11.8), P<0.001), and swallowing (11.0 (8.4 to 13.6), P<0.001). The difference in swallowing scores reached clinical significance (>10 points difference). CONCLUSION: Compared with standard radiotherapy, MRLN sparing radiotherapy showed non-inferiority in terms of risk of local relapse with fewer radiation related toxicity and improved patient reported outcomes in patients with non-metastatic nasopharyngeal carcinoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT03346109.

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma.

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1-associating protein)-mediated TEAD4 m6A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

Current status and temporal trend of disease burden of thyroid cancer in China from 1990 to 2019.

OBJECTIVE: Thyroid cancer has been an increasingly high-profile public health issue. Comprehensive assessment for its disease burden seems particularly important for understanding health priorities and hinting high-risk populations. METHODS: We estimated the age-sex-specific thyroid cancer burden and its temporal trend in China from 1990 to 2019 by following the general methods from the global burden of disease (GBDs) 2019 Study. And Joinpoint regression model, the Cox-Stuart trend test, and Cochran-Armitage test were applied for the analysis of temporal and age trend. The Mantel-Haenszel statistical method was used to compare the gender difference. RESULTS: From 1990 to 2019, the age-standardized incidence rate of thyroid cancer in China has almost doubled to 2.05 per 100,000. Although the mortality rate and DALY rate kept leveling off, they presented a downtrend among females, while an upward trend in males. While the average annual percentage changes of those metrics all became deline since 2010 than the previous years. With age advancing, the rates of incidence, mortality, and DALYs for both sexes all presented linear fashion increases, which was particularly typical among males. CONCLUSION: Given the serious trend and gender-age heterogeneity of Chinese thyroid cancer burden, male gender and advanced age may be related to poor prognosis of thyroid cancer, and strengthening primary prevention and exploring the underlying risk factors should be among the top priorities.

Pinellia ternata attenuates carotid artery intimal hyperplasia and increases endothelial progenitor cell activity via the PI3K/Akt signalling pathway in wire-injured rats.

CONTEXT: Clinically, Pinellia ternata (Thunb.) Breit. (Araceae) (PT) has been widely used in the treatment of atherosclerosis and hyperlipidaemia, but the underlying mechanisms are still not clearly understood. OBJECTIVE: This research was conducted to confirm the mechanism by which PT affects carotid artery intimal hyperplasia. MATERIALS AND METHODS: An intestinal hyperplasia Sprague-Dawley rat model was established by carotid artery injury. The rats were randomly divided into five groups (n = 8): sham, model, PT (with daily intragastric administration of 10 g/mL/kg PT tubers water extract), PT+LY294002 (with intraperitoneal injection of 50 mg/kg LY294002 + 10 g/mL/kg PT) and endothelial progenitor cells (EPCs) (with injection of 5 × 105/cells), and treated for 4 or 8 weeks. RESULTS: HE staining showed that PT attenuated intimal hyperplasia. RT-PCR, Western blotting and immunohistochemistry showed that PT increased the expression of vascular endothelial growth factor (VEGF) and eNOS in the atherosclerotic carotid artery. PT increased the Dil-acLDL+/FITC-UEA-1+ population (from 0.41 ± 0.085% to 0.60 ± 0.092%) in the blood, decreased TCHO, TG, LDL-C, IL-6 and TNF-α levels, and increased HDL-C and IL-10 levels in the blood. However, these changes were reversed by the PI3K/Akt pathway inhibitor LY294002. DISCUSSION AND CONCLUSIONS: PT can be developed as an atherosclerosis and carotid intimal hyperplasia treatment drug. Therefore, further study will focus on the effects of PT on intimal hyperplasia in wire-injured atherosclerosis patients and explore in depth some other relevant molecular mechanisms.

Lifestyles correlate with stroke recurrence in Chinese inpatients with first-ever acute ischemic stroke.

OBJECTIVES: The previous studies have shown that recurrent stroke (RS) adversely affects the life of survivors of ischemic stroke (IS). However, lifestyle associated with RS has received a little systematic study in Chinese Han patients. We aimed to perform a comprehensive assessment of lifestyle and the potential risk factors associated with RS in Chinese Han inpatients with first-ever acute ischemic stroke by conducting a long-term follow-up. METHODS: Using a prospective and longitudinal design, we recruited 421 patients with first-ever acute ischemic stroke who were consecutively admitted to the Acute Stroke Unit between November 2012 and January 2014. Demographic data, vascular risk factors, previous Rankin scale score, and etiology were collected at study intake. Multivariable Cox regression model was used to investigate the influencing factors for RS. RESULTS: Fifty-seven (13.5%) patients experienced RS during the 1-year follow-up period. Multivariable Cox regression analysis revealed that smoking [hazard ratio (HR), 2.153; 95% confidence interval (CI), 1.263-3.671], high-density lipoprotein cholesterol (HDL) (HR 0.438; 95% CI 0.211-0.911), housework (HR 0.488; 95% CI 0.256-0.933), ischemic heart disease (IHD) (HR 2.998; 95% CI 1.281-7.020), daily consumption of fresh fruits (HR 0.477; 95% CI 0.278-0.819), and good sleep quality (HR 0.375; 95% CI 0.216-0.650) were associated with RS among stroke patients. CONCLUSIONS: Our results suggest that healthy lifestyle (high fruit intake, smoking cessation, housework, and good sleep quality), higher HDL levels, and lack of IHD may be associated with a lower risk of RS in patients with first-onset IS.

Hydrogen sulfide prevents homocysteine­induced endoplasmic reticulum stress in PC12 cells by upregulating SIRT­1.

It was previously confirmed that hydrogen sulfide (H2S) has a neuroprotective effect, preventing homocysteine­induced neurotoxicity. However, the exact molecular mechanisms underlying this protective effect remain to be fully elucidated. Endoplasmic reticulum (ER) stress contributes to homocysteine­induced neurotoxicity. Silent mating type information regulator 2 homolog 1 (SIRT­1) can attenuate ER stress, exerting its neuroprotective effect. Therefore, the present study aimed to investigate whether H2S protects PC12 cells against homocysteine­induced ER stress and whether SIRT­1 mediates this protective effect of H2S. Western blotting was used to detect the expression of SIRT­1, glucose­regulated protein 78 (GRP78), and cleaved caspase­12 in PC12 cells. It was observed that sodium hydrosulfide (NaHS), an exogenous H2S donor, significantly attenuated the homocysteine­induced ER stress responses, including increases in the protein expression levels of GRP78 and cleaved caspase­12. Simultaneously, NaHS upregulated the expression of SIRT­1 and reversed the homocysteine­induced downregulation of SIRT­1 in PC12 cells. Sirtinol, a specific inhibitor of SIRT­1, eliminated the protective effects of H2S in homocysteine­induced ER stress. These data indicated that H2S prevented homocysteine­induced ER stress via enhancing the expression of SIRT­1. These findings offer novel insight into the protective mechanisms of H2S against homocysteine­induced neurotoxicity.

A case report of syndrome of inappropriate antidiuretic hormone secretion with Castleman's disease and lymphoma.

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in hospitalized patients and is often described in patients with small-cell carcinoma of the lung. In this report, we described both Castleman's disease and lymphoma coexisting in one patient with SIADH. CASE PRESENTATION: A 70-year-old Chinese woman with a history of diabetes mellitus and insulin therapy had severe hyponatremia and gastrointestinal symptoms. Through a series of examinations, common causes such as pulmonary carcinoma were excluded. An abdominal mass was detected by computed tomography. Although the peripheral lymph node biopsy showed the pathological result as Castleman's disease, the pathology of the abdominal lymph node revealed diffuse large B-cell lymphoma. After chemotherapy, the hyponatremia was treated during a period of follow-up. CONCLUSION: This patient presented with the rare clinical condition of inappropriate antidiuretic hormone secretion alongside Castleman's disease and lymphoma. Asymptomatic hyponatremia may persist for some time suggesting that clinical physicians should pay attention to the mild cases of hyponatremia. We also hypothesized that Castleman's disease is a condition of pre-lymphoma with both having the ability to cause SIADH. The possibility of lymphoma as well as Castleman's disease triggering the development of SIADH should also be taken into consideration for conducting recurrent biopsies.

[Effect of 5-fluorouracil in combination with Astragalus membranaceus on amino acid metabolism in mice model of gastric carcinoma].

OBJECTIVE: To study the effect of 5-fluorouracil-FU in combination with astragalus membranaceus(AM) on amino acid metabolism in mice model of gastric carcinoma induced by 3-methylcholanthrene(MC). METHODS: Mice gastric carcinoma models were established by 3-methylcholanthrene induction and randomly divided into different groups, and received 5-FU treatment (group A) 5-FU plus AM (group B), 5-FU plus a high dose of AM(group C), no treatment (group D). Normal mice were used as control (group N). Free amino acid in the tumor specimens were examined. RESULTS: The levels of free Valine, Methionine, Leucine, Arginine and cystine in the tumor specimens in group D were significantly higher than that in group N(P< 0.05). The levels of free serine in group A, B, C, D were significantly higher than that in group N. The levels of free glutamic acid in group A, B were significantly higher than that in group N(P< 0.05). The levels of free proline in group C, D were significantly higher than that in group P, N(P< 0.05). CONCLUSIONS: The increasing levels of free serine and proline in tumor specimens in gastric cancer mice model reveals metabolic disturbance of amino acid. 5-FU plus astragalus membranaceus can decrease the level of free glutamic acid in the mice models, and inhibit tumor growth.

[A study on correlation of hepatic metastasis of colorectal cancer to vascular endothelial growth factor, angiopoietin-2, and fibronectin].

OBJECTIVE: To study the correlation of hepatic metastasis of colorectal cancer to vascular endothelial growth factor (VEGF), angiopoietin- 2 and fibronectin (FN). METHODS: The transcription and expression of VEGF, angiopoietin- 2 and FN were detected by semiquantitative reverse transcription- polymerase chain reaction (SQRT- PCR) and immunohistochemical staining in the specimens from sixty patients with colorectal cancer. RESULTS: The mRNA transcription and expression levels of VEGF, angiopoietin- 2 and FN in colorectal cancer tissues were obviously higher than those in paratumor normal tissues P< 0.05. The transcription and expression levels of VEGF were correlated with tumor invasion P< 0.05,Dukes' stage P< 0.05,and lymph node and/or hepatic metastasis P< 0.05. Angiopoietin expression and transcription levels were correlated with tumor differentiation. The expression of FN in extra cellular matrix (ECM) was significantly higher (P< 0.05),whereas ECM in basement membrane was significantly lower in cancer tissues than that in paratumor normal tissues (P< 0.05),which both were correlated with tumor invasion P< 0.05,Dukes' stage P< 0.05,and lymph node metastasis P< 0.05. Absence of FN protein in basement membrane was also correlated with hepatic metastasis. CONCLUSION: Colorectal cancer cells can secrete VEGF and contribute to metastasis and proliferation of tumor by stimulating the growth of tumor vessel. Both of VEGF and angiopoietin- 2 contribute to angiogenesis and the decrease of FN in basement membrane of cancer tissue is an important primary factor of hepatic metastasis.

[Therapeutic efficacy of bipolar plasmakinetic technique compared with transurethral resection on benign prostate hyperplasia].

OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with the bipolar plasmakinetic technique (PKRP) compared with the transurethral resection (TURP) in the treatment of benign prostate hyperplasia (BPH). METHOD: Four hundred BPH patients with matched lesions were divided into 2 groups: 200 patients, aged 74.1 (58-91), underwent transurethral prostatectomy with PKRP, and 200 patients, aged 73.8 (56-90), underwent TURP. RESULT: In the PKRP group the average IPSS decreased from 27.1 +/- 4.5 preoperatively to 11.3 +/- 3.4 postoperatively 6 months after (P < 0.01), the. average maximum flow-rate Q (max) increased from 6.1 +/- 2.4 ml/s preoperatively to 18.6 +/- 3.5 ml/s postoperatively (P < 0.01), and the average residual urine (RU) reduced from 102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). However in the TURP group the average IPSS decreased from 26.9 +/- 4.2 preoperatively to 10.8 +/- 3.6 6 months after the operation (P < 0.01), the Q (max) increased from 5.7 +/- 2.4 ml/s preoperatively to 19.1 +/- 3.7 ml/s postoperatively (P < 0.01), and the average RU decreased from 102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). There were no significant differences in these parameters between these 2 groups (all P > 0.05). The average catheter retention time was 31.5 h in the PKRP, significantly shorter than that in the TURP group (61.5 hours, P < 0.01). The incidence rate of post-operational asynodia in the PKRP group was 14.3%, not significantly different from that in the TURP group (15.2%, P > 0.05). During the operation no hemorrhage or transurethral resection syndrome (TURS) occurred in the PKRP group, however, there were 5 cases of TURS and 18 cases of blood transfusion in the TURP group. CONCLUSION: PKRP has the same therapeutic efficacy as TURP on BPH. Moreover, it was more cheaper and with lower complication than TURP.