Hand-sewn gastrojejunal anastomosis reduces delayed gastric emptying after pancreaticoduodenectomy: A single-center retrospective clinical study of 1,077 consecutive patients.

BACKGROUND: Hand-sewn anastomosis and stapled anastomosis are the 2 main types of gastrojejunal anastomotic methods in pancreaticoduodenectomy. There is ongoing debate regarding the most effective anastomotic method for reducing delayed gastric emptying after pancreaticoduodenectomy. This study aims to identify factors that influence delayed gastric emptying after pancreaticoduodenectomy and assess the impact of different anastomotic methods on delayed gastric emptying. METHODS: The study included 1,077 patients who had undergone either hand-sewn anastomosis (n = 734) or stapled anastomosis (n = 343) during pancreaticoduodenectomy between December 2016 and November 2021 at our department. We retrospectively analyzed the clinical data, and a 1:1 propensity score matching was performed to balance confounding variables. RESULTS: After propensity score matching, 320 patients were included in each group. Compared with the stapled anastomosis group, the hand-sewn anastomosis group had a significantly lower incidence of delayed gastric emptying (28 [8.8%] vs 55 [17.2%], P = .001) and upper gastrointestinal tract bleeding (6 [1.9%] vs 17 [5.3%], P = .02). Additionally, the hand-sewn anastomosis group had a significantly reduced postoperative length of stay and lower hospitalization expenses. However, the hand-sewn anastomosis group had a significantly longer operative time, which was consistent with the analysis before propensity score matching. Logistic regression analysis showed that stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula were independent prognostic factors for delayed gastric emptying. CONCLUSION: Hand-sewn anastomosis was associated with a lower incidence rate of clinically relevant delayed gastric emptying after pancreaticoduodenectomy. Stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula could increase the incidence of postoperative clinically relevant delayed gastric emptying. Hand-sewn anastomosis should be considered by surgeons to reduce the occurrence of postoperative delayed gastric emptying and improve patient outcomes.

Resveratrol alleviates oxidative stress induced by oxidized soybean oil and improves gut function via changing gut microbiota in weaned piglets.

BACKGROUND: Oxidized soybean oil (OSO) has been shown to impair growth and exacerbate inflammation, leading to intestinal barrier injury in animals. Recent evidence suggests important roles for resveratrol (RES) in the promoting growth performance, antioxidant capacity, anti-inflammatory, and regulate intestinal barriers in animals. Therefore, The objectives of this study are to investigate the effects of dietary RES (purity 98%) supplementation on the growth performance, antioxidant capacity, inflammatory state, and intestinal function of weaned piglets challenged with OSO. METHODS: A total of 28 castrated weaned male piglets with a similar body weight of 10.19 ± 0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 7 replications per treatment and 1 piglet per replicate. Treatments were arranged as a 2 × 2 factorial with oil type [3% fresh soybean oil (FSO) vs. 3% OSO] and dietary RES (0 vs. 300 mg/kg). RESULTS: The results showed that relative to the FSO group, OSO stress tended to decrease the average daily feed intake (ADFI), and decreased the activity levels of lipase, villus/crypt ratio (VCR), the mRNA expression of FABP1, SOD2, IL-10 and ZO-1 in the jejunum, and SOD2, GPX1, occludin and ZO-1 in the colon, the levels of acetic acid in the colonic digesta, whereas up-regulated the mRNA expression of IL-1ß and TNF-α in the jejunum (P < 0.05). Moreover, dietary supplementation with RES increased ether extract (EE), the activity levels of sucrase, lipase, α-amylase, villus height (VH) and VCR, the mRNA expression of FABP1, SOD2, IL-10 and occludin in the jejunum, and FABP1, PPAR-γ, GPX1, occludin and ZO-1 in the colon, and the abundance of Firmicutes, acetic and propionic acid, but decreased the levels of D-lactic acid in the plasma, the abundance of Bacteroidetes in the colonic digesta of weaned piglets compared to the non-RES group (P < 0.05). Meanwhile, in the interaction effect analysis, relative to the OSO group, dietary RES supplementation in the diets supplemented with OSO increased the activity levels of trypsin, VH in the jejunum, the abundance of Actinobacteria, the levels of butyric acid of weaned piglets, but failed to influence the activity levels of trypsin and VH, Actinobacteria abundance, the levels of butyric acid when diets were supplemented with FSO (interaction, P < 0.05). Relative to the OSO group, dietary RES supplementation in the diets supplemented with OSO decreased the activity levels of DAO in the plasma of weaned piglets but failed to influence the activity levels of DAO when diets were supplemented with FSO (interaction, P < 0.05). Relative to the FSO group, dietary RES supplementation in the diets supplemented with FSO decreased the level of propionic acid, whereas RES supplementation failed to influence the level of propionic acid when the diet was supplemented with OSO (interaction, P < 0.01). CONCLUSIONS: Inclusion of OSO intensified inflammatory states and impaired the intestinal health characteristics of weaned piglets. Dietary RES supplementation improved the antioxidant capacity, anti-inflammatory activity, and intestinal morphology. Further studies showed that the protective effects of RES on gut health could be linked to the decreased abundance of Prevotella_1, Clostridium_sensu_stricto_6, and Prevotellaceae_UCG003 and increased levels of acetic and propionic acid.

Perinatal exposure to high concentration glyphosate-based herbicides induces intestinal apoptosis by activating endoplasmic reticulum stress in offspring.

Glyphosate-based herbicides (GBHs), the most widely used pesticide worldwide, have been reported to impair organ function in humans and animals. However, research on the effect of maternal GBHs exposure on the intestinal health of offspring has received little attention. Based on the glyphosate limits defined by Codex Alimentarius Commission and European Food Safety Authority, this study established pregnant sow exposure models to investigate the influence of low (L-GBHs, 20 mg/kg) and high concentration GBHs (H-GBHs, 100 mg/kg) on the intestinal health of offspring and proposed the protective mechanism mediated by betaine. The results showed that the intestinal morphology and barrier function of suckling piglets were damaged in the H-GBHs group. H-GBHs increased the activity of glutathione peroxidase (GPX) and levels of methane dicarboxylic aldehyde (MDA), hydrogen peroxide (H2O2) and inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10)) in suckling piglets and activated Nrf2-mediated antioxidant signaling pathway. Subsequently, we found that exposure to H-GBHs triggered endoplasmic reticulum stress (ERS) and further induced apoptosis by upregulating the expression of Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and Caspase12. Moreover, H-GBHs exposure perturbed mitochondrial membrane fusion and electron transport in mitochondrial respiratory chains by increasing the mRNA expression of mitofusin-2 (MFN2) and succinate dehydrogenase subunit A (SDHA), causing mitochondrial dysfunction. Dietary supplementation with betaine provided modest protection against GBHs-induced intestinal damage in suckling piglets. These findings reveal the mechanism of GBHs-induced intestinal damage in offspring, improving our understanding of the risk of GBHs exposure in pregnant women and suggesting the potential protective effects of betaine against GBHs poisoning.

Perinatal exposure to glyphosate-based herbicides impairs progeny health and placental angiogenesis by disturbing mitochondrial function.

Glyphosate-based herbicides (GBHs) are the most widely used pesticide worldwide and can provoke placental injury. However, whether and how GBHs damage angiogenesis in the placenta is not yet known. This work evaluated the safety of glyphosate on pregnant sows based on the limit level by governments and investigated the effects and mechanism of Low-GBHs (20 mg/kg) and High-GBHs (100 mg/kg) exposure on placental angiogenesis. Results showed that gestational exposure to GBHs decreased placental vessel density and cell multiplication by interfering with the expression of VEGFA, PLGF, VEGFr2 and Hand2 (indicators of angiogenesis), which may be in relation to oxidative stress-induced disorders of mitochondrial fission and fusion as well as the impaired function of the mitochondrial respiratory chain. Additionally, GBHs destroyed barrier function and nutrient transport in the placenta, and was accompanied by jejunum oxidative stress in newborn piglets. However, GBHs exposure had no significant differences on sow reproductive performance. As a natural antioxidant, betaine treatment protected placenta and newborn piglets against GBHs-induced damage. In conclusion, GBHs impaired placental angiogenesis and function and further damaged the health of postnatal progeny, these effects may be linked to mitochondrial dysfunction. Betaine treatment following glyphosate exposure provided modest relief.

Triport periareolar thoracoscopic surgery versus right minithoracotomy for repairing atrial septal defect in adults.

OBJECTIVES: Our goal was to investigate the safety and feasibility of triport periareolar thoracoscopic surgery (TPTS) and its advantages in repairing adult atrial septal defect. METHODS: Between January 2017 and January 2020, a total of 121 consecutive adult patients underwent atrial septal defect closure in our institution. Of these, 30 patients had TPTS and 31 patients had a right minithoracotomy (RMT). Operational data and clinical outcomes were compared between the 2 groups. RESULTS: The total operation time, cardiopulmonary bypass time and aortic cross-clamp time in the TPTS group were slightly longer than those in the RMT group, but there were no differences between the 2 groups. Compared with the RMT group, the TPTS group showed a decrease in the volume of chest drainage in 24 h (98.6 ± 191.2 vs 222.6 ± 217.2 ml; P = 0.032) and a shorter postoperative hospital stay (6.5 ± 1.5 vs 8.0 ± 3.7 days; P = 0.042). The numeric rating scale on postoperative day 7 was significantly less in the TPTS group than in the RMT group (2.82 ± 1.14 vs 3.56 ± 1.42; P = 0.034). The patient satisfaction scale for the cosmetic results in the TPTS group was significantly higher than in the RMT group (4.68 ± 0.55 vs 4.22 ± 0.76; P = 0.012). No differences were found in postoperative complications. No in-hospital death or major adverse events occurred in the 2 groups. CONCLUSIONS: TPTS is safe and feasible for the closure of adult atrial septal defect. Compared with RMT, it has been associated with less pain and better cosmetic outcomes.

Amentoflavone Promotes Apoptosis in Non-Small-Cell Lung Cancer by Modulating Cancerous Inhibitor of PP2A.

Non-small-cell lung cancer (NSCLC) is one of the most common human malignancies. Amentoflavone (AF) is one of bioflavonoid compounds isolated from Selaginella tamariscina Spring. This study was designed to examine the effect of AF on NSCLC. Our results indicated that AF decreased cell viability of both H1299 and H358 cells. Colony formation assay also showed that AF was able to suppress the anchorage-independent growth of NSCLC cells. AF also triggered cell cycle arrest by downregulating cyclin D1, CDK4, and CDK6. The pro-apoptotic activity of AF was confirmed by Hoechst staining and flow cytometry. The effect of AF on activation of caspase-3, upregulation of Bax, and downregulation of Bcl-2 was examined by western blot. The anti-growth and pro-apoptotic activities of AF were further validated in xenograft murine model. iTRAQ assay showed that cancerous inhibitor of PP2A (CIP2A) expression was markedly downregulated by AF treatment in H1299 cells. In addition, qRT-PCR and western blot also showed that AF was able to dose-dependently inhibit CIP2A expression. Meanwhile, the activity of protein phosphatase 2A (PP2A) was enhanced by AF treatment. The mRNA and protein expression of CIP2A as well as PP2A activity in xenograft tumor tissue were examined, which indicated that the in vivo anticancer activity of AF was associated with downregulation of CIP2A and reactivation of PP2A. Moreover, our results showed that the anti-growth and pro-apoptotic activities of AF were augmented by CIP2A knockdown and attenuated by ectopic CIP2A expression. Our results indicated that AF exhibited anticancer activity in NSCLC by targeting CIP2A. Anat Rec, 302:2201-2210, 2019. © 2019 American Association for Anatomy.

Overexpression of microRNA-24 increases the sensitivity to paclitaxel in drug-resistant breast carcinoma cell lines via targeting ABCB9.

Paclitaxel has been widely used in the treatment of breast cancer. However, the development of drug resistance often increases the failure of chemotherapy. Growing evidence has reported the significant role of microRNAs (miRs) in drug resistance. The present study identified that miR-24 was significantly downregulated in paclitaxel-resistant (PR) breast cancer patients and in MCF-7/PR human breast carcinoma cells, and that overexpression of miR-24 could increase the effect of paclitaxel on drug-resistant breast carcinoma cells. Furthermore, miR-24 could directly bind to the 3'-untranslated region of ATP binding cassette B9 to downregulate its expression, thereby reducing drug transportation and improving the anti-tumor effect of paclitaxel on breast cancer cells. In vivo experiments also demonstrated that overexpression of miR-24 could increase the sensitivity of drug-resistant MCF-7 cells to paclitaxel. In conclusion, the present results suggested a novel function for miR-24 in reducing paclitaxel resistance in breast cancer, which may be of important clinical significance.

A single institution experience using the LigaSure vessel sealing system in video-assisted thoracoscopic surgery for primary spontaneous pneumothorax.

This study sought to report our 6-year experience with the LigaSure vessel sealing system (LVSS) in video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax. A series of 180 consecutive patients with primary spontaneous pneumothorax were operated on in our institution from May 2005 to December 2010. Intraoperatively, large lesions (bullae or blebs) with a diameter more than 2 cm were resected by staplers, and the residual lesions were treated by LVSS. LVSS was also used to ablate the apical area when no lesions were found. Conventional apical pleural abrasion was done in all cases. All patients were successfully treated using VATS with minimal perioperative bleeding. The mean operating time was 76 minutes (range, 43-160 minutes) for single-side procedures and 169 minutes (range, 135-195 minutes) for bilateral procedures, the mean number of applied staples was 1.93 per patient (range, 0-8 days), the duration of drainage was 3.8 days (range, 2-15 days), and the duration of hospital stay was 5.8 days (range, 3-16 days). Postoperative complications included persistent air leak (> 5 days) in 11 cases (6.1%) and residual pneumothorax in 6 (3.3%). None required reoperation. The mean duration of follow-up was 57 months (range, 24-105 months). Recurrence was seen in three cases (1.7%), and all underwent another operation thereafter. None of the lesions in the relapse cases received ablation with LVSS in the first operation. LVSS can optimize VATS for primary spontaneous pneumothorax and reduces the use of single-use staples. The method is safe, easy to use, and cost-effective and produces satisfactory results.

Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-ß1 levels in serum of patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. METHODS: Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-ß1 in serum using an enzyme immunosorbent assay. RESULTS: NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-ß1 in blood. CONCLUSIONS: These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-ß1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.

[Clinical observation of the immediate breast reconstruction following breast-conserving surgery for centrally located breast cancer].

OBJECTIVE: To investigate the clinical efficacy of the immediate breast reconstruction following breast-conserving surgery for centrally located breast cancer. METHODS: From January of 2006 through December of 2011, 30 women with centrally located breast cancer of stage I or II was treated by breast-conserving surgery removing or not removing the nipple-areola complex. All the patients received immediate breast reconstruction with adjacent gland tissue flap or latissimus dorsi myocutaneous flap. The breast shape and complication were observed. All the patients were followed up. RESULTS: The thirty women underwent the breast-conserving surgery successfully, in which 12 cases received immediate breast reconstruction with adjacent gland tissue flap and 18 cases received immediate breast reconstruction with latissimus dorsi myocutaneous flap. The superior rate of the aesthetic effect was 90% (27/30) according to JCRT in one week or six months after surgery. No recurrence and metastasis were observed after a median follow-up of 38 months ( range 4-72 months). CONCLUSION: The immediate breast reconstruction following breast-conserving surgery for centrally located breast cancer at early stage is satisfactory for the aesthetic result and clinical efficacy, and deserves further clinical application.

Intracellular lactate signaling cascade in atrial remodeling of mitral valvular patients with atrial fibrillation.

BACKGROUND: Atrial remodeling has emerged as the structural basis for the maintenance and recurrence of atrial fibrillation. Lactate signaling cascade was recently linked to some cardiovascular disorders for its regulatory functions to myocardial structural remodeling. It was hypothesized that lactate signaling cascade was involved in the maintenance and recurrence of atrial fibrillation by regulating atrial structural remodeling. METHODS: Biopsies of right atrial appendage and clinical data were collected from sex- and age-matched 30 persistent atrial fibrillation, 30 paroxysmal atrial fibrillation, 30 sinus rhythm patients undergoing isolated mitral valve surgery and 10 healthy heart donors. RESULTS: Atrial fibrillation groups had higher atrial lactate expression and this upregulated expression was positively correlated with regulatory indicators of atrial structural remodeling as reflected by severe oxidative stress injury and mitochondrial control of apoptosis. CONCLUSIONS: The present findings suggest a potential role for lactate signaling cascade in the maintenance and recurrence of atrial fibrillation and possibly represent new targets for therapeutic intervention in this disorder.

Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-ß1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation.

OBJECTIVES: The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). BACKGROUND: AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. METHODS: Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-ß1 (TGF-ß1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. RESULTS: Calreticulin, integrin-α5, and TGF-ß1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-ß1 expression, while calreticulin expression correlated with integrin-α5 and TGF-ß1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. CONCLUSIONS: Calreticulin, integrin-α5, and TGF-ß1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients.

Inflammatory myofibroblastic tumor of the breast coexisting with breast cancer: a case report.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is an uncommon low-risk lesion with only a few cases described in the literature. CASE REPORT: Here, we report a unique case of an IMT coexisting with breast cancer. Modified radical mastectomy was performed, followed by TAC chemotherapy (taxotere, adriamycin and cyclophosphamide). At the 2-year follow-up, the patient continues to be disease free. CONCLUSION: At the preoperative stage, definitive diagnoses of masses are extremely difficult; surgery is advised only after the diagnosis is confirmed by pathological examination.

Calcium- and integrin-binding protein-1 and calcineurin are upregulated in the right atrial myocardium of patients with atrial fibrillation.

AIMS: The aim of this study was to determine whether altered expression and distribution of calcium- and integrin-binding protein-1 (CIB1) is involved in the pathogenesis of different types of patients with atrial fibrillation (AF) associated with valvular heart disease (VHD). METHODS AND RESULTS: Right atrial specimens obtained from 65 patients undergoing valve replacement surgery were divided into three groups: sinus rhythm group (n= 24), paroxysmal atrial fibrillation group (PaAF; n= 10), and persistent atrial fibrillation group (PeAF; AF lasting >6 month; n= 31). The expression levels of mRNA and protein content for CIB1, calcineurin B, calcineurin A, and Na(+)-Ca(2+) exchanger-1 (NCX1) were measured. We also measured the combination of CIB1 with calcineurin B, L-type Ca(2+) channel, and NCX1 using immunoprecipitation. Expression of mRNA and protein content of CIB1, calcineurin B, calcineurin A, and NCX1 was increased in the AF group. Calcium- and integrin-binding protein-1 interacted with calcineurin B and L-type Ca(2+) channel. Surprisingly, CIB1 also combined with NCX1. CONCLUSIONS: The CIB1 and calcineurin expression was increased in AF atrial tissue and was related to the type of AF. This finding suggests that CIB1 may be involved in the pathogenesis of AF in VHD patients.

Polymorphisms in genes involved in drug detoxification and clinical outcomes of anthracycline-based neoadjuvant chemotherapy in Chinese Han breast cancer patients.

BACKGROUND: The large individual variability for anticancer drugs in both outcome and toxicity risk makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect. AIMS: This work aimed to evaluate the importance of genetic polymorphisms involved in drug detoxification to predict clinical outcomes of anthracycline-based neoadjuvant chemotherapy for breast cancer. RESULTS: GSTP1 313 AA genotype was associated with a poor clinical response relative to G allele carrier (58.4% vs 80.8%; p = 0.006), and MDR1 3435 TT genotype had a worse response compared with C allele carrier (33.3% vs 71.2% p = 0.001). Patients with both the adverse genotypes of GSTP1 314AA and MDR 3435TT showed the worst therapy efficacy in all (14.3%; p = 0.000). Kaplan-Meier survival analysis showed that the patients with no adverse genotype were associated with decreased hazard of relapse (p = 0.002), compared with those with 1 or 2 adverse genotypes. Multivariate analysis demonstrated that clinical response and no adverse genotype was independent predictors of disease-free survival (DFS). METHODS: Genotyping was performed by allele-specific oligonucleotide ligation reaction (MnSOD, CAT, GSTP1), multiplex PCR (GSTM1, GSTT1) or PCR-RFLP (MDR1). Based on 153 patients received anthracycline-based neoadjuvant chemotherapy, these genotypes or their combinations in relation to treatment-related response, hematologic toxicity and DFS were investigated. CONCLUSIONS: These results suggest that polymorphisms in GSTP1 and MDR1 may help to predict clinical response and DFS of anthracycline-based chemotherapy, and a polygenic pathway approach should provide more useful information. The findings required independent prospective confirmation.

Circulating levels of angiogenic cytokines in advanced breast cancer patients with system chemotherapy and their potential value in monitoring disease course.

PURPOSE: The low-dose metronomic chemotherapy was reported to inhibit directly tumor angiogenesis or VEGF secretion. The study aimed to seek for this effect of system chemotherapy by observing the changes in serum levels of angiogenic cytokines during treatment and assessing their value in monitoring the advanced breast cancer. METHODS: In sixty-one patients with advanced breast cancer, serum levels of vascular endothelial growth factor (VEGF) and endostatin (ES) were compared at baseline (B0), after one cycle (B1), after 3 cycles (B3), and after 5-6 cycles (B5-6) of system chemotherapy using a quantitative ELISA. Data were correlated with treatment response and total survival. RESULTS: The response to chemotherapy did not correlate with serum VEGF level before therapy or after one cycle, but the changes in VEGF levels after 3 cycles and 5-6 cycles showed good association with clinical responses, i.e., the patients with disease control had a decreased VEGF value, whereas the progressive patients had an increased value. The Cox proportional hazard model revealed that a normalized VEGF level after therapy and an increase in VEGF level after 5-6 cycles were independent predictors for survival. CONCLUSIONS: System chemotherapy for advanced breast cancer lead to a significant decrease in serum VEGF level in patients with disease control, and this anti-VEGF efficacy may be mainly due to the reduction in tumor burden. Sequential measurement of serum VEGF could be useful for evaluating treatment efficacy and prognosis.

[Lesion localization and surgical resection for non-palpable breast cancer].

OBJECTIVE: To investigate the methods of lesion localization and surgical treatment for non-palpable breast cancer, presented with only small calcification lesion on the images. METHODS: From November 2003 to August 2007, 61 patients with non-palpable lesion were finally pathologically diagnosed as early breast cancer (T1-2N0M0), based on the small calcification lesions shown by full field digital mammography (FFDM) through molybdenum target, and the rich blood supply shown by type-B ultrasonic examination. Accurate lesion-localization prior to surgical resection was conducted, and sample re-examination by FFDM was done after resection. Patients with single lesion underwent breast-conserving surgery, precise excision with the aid of image-guided wire localization, and stage I breast reconstruction was performed simultaneously using wide-based gland-tissue flap. Patients with multiple lesions received modified radical mastectomy. RESULTS: Among the 50 patients treated with breast-conserving surgery, the accuracy of localization for lesions was 100% (50/50), and all lesions were excised completely with a negative margin proven by FFDM re-examination and pathological examination. The superior rate of mammaplasty was 86.0% (43/50) according to JCRT criteria, with a compliance difference of 1.5 cm. Modified radical mastectomy was performed in 11 patients. The follow-up period in this series was from 6 to 58 months with a mean follow-up time of 39 months. Distant metastases were detected in only one patient and local recurrence was not observed yet. CONCLUSION: Lesion localization by FFDM in patients with non-palpable breast cancer is accurate and practical. In patients with single lesion, breast-conserving resection followed by synchronous stage I breast reconstruction with wide-based gland-tissue flap is appropriate.

Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women.

PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings.

A polymorphism in Werner syndrome gene is associated with breast cancer susceptibility in Chinese women.

RecQ helicases play a central role in maintaining genome stability and may interact with some important cancer-related proteins such as BRCA1. Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer. In this case-control study of 1,004 breast cancer cases and 1,008 controls, we tested the hypothesis that non-conservative amino acid exchanges in WRN (leu1074Phe), BLM (Met298Thr) and BRCA1 (Pro871Leu) are independently or jointly associated with the risk of breast cancer in Chinese women. We found that the variant genotype of WRN Leu1074Phe was associated with a 1.36-fold significantly increased risk of breast cancer (OR = 1.36, 95% CI = 1.06-1.74). Moreover, a significant gene-environment interaction was evident between WRN leu1074Phe and age at menarche (P (int) = 0.02). Subjects carrying Phe/Phe genotype and with earlier age at menarche had 3.58-fold increased risk of breast cancer (OR = 3.58, 95% CI = 2.54-5.05). However, we did not find the significant main effect of polymorphisms in BLM and BRCA1 and also no locus-locus interactions were identified between WRN, BLM and BRCA1. These findings indicate that WRN leu1074Phe variant may contribute to the susceptibility of breast cancer in Chinese women.