Effects of bariatric surgery on breast density in adult obese women: systematic review and meta-analysis.

Introduction: Bariatric surgery is one of the most effective methods for treating obesity. It can effectively reduce body weight and reduce the incidence of obesity-related breast cancer. However, there are different conclusions about how bariatric surgery changes breast density. The purpose of this study was to clarify the changes in breast density from before to after bariatric surgery. Methods: The relevant literature was searched through PubMed and Embase to screen for studies. Meta-analysis was used to clarify the changes in breast density from before to after bariatric surgery. Results: A total of seven studies were included in this systematic review and meta-analysis, including a total of 535 people. The average body mass index decreased from 45.3 kg/m2 before surgery to 34.4 kg/m2 after surgery. By the Breast Imaging Reporting and Data System score, the proportion of grade A breast density from before to after bariatric surgery decreased by 3.83% (183 vs. 176), grade B (248 vs. 263) increased by 6.05%, grade C (94 vs. 89) decreased by 5.32%, and grade D (1 vs. 4) increased by 300%. There was no significant change in breast density from before to after bariatric surgery (OR=1.27, 95% confidence interval (CI) [0.74, 2.20], P=0.38). By the Volpara density grade score, postoperative volumetric breast density increased (standardized mean difference = -0.68, 95% CI [-1.08, -0.27], P = 0.001). Discussions: Breast density increased significantly after bariatric surgery, but this depended on the method of detecting breast density. Further randomized controlled studies are needed to validate our conclusions.

A novel refined classification system for type 2 diabetes in adults: A Chinese retrospective cohort study.

AIMS: We propose a simple type 2 diabetes mellitus (T2DM) classification method based on fasting C-peptide (FCP) levels and examined its feasibility and validity. METHODS: Adult T2DM patients first diagnosed in our tertiary care centre from January 2009 to January 2020 were included. Patients were followed until January 2021; their clinical characteristics, chronic complications, treatment regimen, and glycaemic control were compared. RESULTS: In total, 5644 T2DM patients were included. Three subgroups were established based on FCP levels: subtype T1 (FCP ≤ 1.0 µg/L), 1423 patients (25.21%); subtype T2 (FCP 1.0-2.5 µg/L), 2914 patients (51.63%); and subtype T3 (FCP ≥ 2.5 µg/L), 1307 patients (23.16%). T1 was characterised by older age, lower body mass indices, higher initial glycosylated haemoglobin (HbA1c) levels, and the lowest homoeostatic model assessment 2 estimates of ß-cell function (HOMA2-ß) and HOMA2-insulin resistance at baseline. The T3 group's clinical characteristics were opposite to those of T1. T3 patients showed higher incidence rates and risks of diabetic kidney disease, diabetic peripheral vascular disease, and non-alcoholic fatty liver, while the risks of diabetic retinopathy and diabetic peripheral neuropathy were highest in T1. Insulin, glycosidase inhibitors, and thiazolidinedione were the most frequently used drugs, but the use of metformin, dipeptidyl peptidase-4 inhibitor, and insulin secretagogue drugs was slightly lower in T1. T1 maintained higher HbA1c levels throughout follow-up. Overall HbA1c fluctuations were more significant in T3 than in T1 and T2. CONCLUSIONS: The new adult T2DM classification is simple and clear and will help classify different T2DM clinical characteristics and guide treatment plans.

Changes in gut microbiota, metabolite SCFAs, and GPR43 expression in obese diabetic mice after sleeve gastrectomy.

AIMS: To evaluate changes in short-chain fatty acid levels and G protein-coupled receptor 43 expression and distribution in gut microbiota and explore their relationships in obese diabetic mice after sleeve gastrectomy. METHODS AND RESULTS: Diet-induced obese mice and obese diabetic ob/ob mice were established. Changes in glucose metabolism, lipid metabolism, gut microbiota, metabolite short-chain fatty acids, and G protein-coupled receptor 43 expressions were assessed in both models 10 weeks postoperatively. Mice that underwent sleeve gastrectomy exhibited sustained weight loss and reduced glucose, insulin, leptin, and cholesterol levels. Metagenomic sequencing revealed significant characteristic alterations in gut microbiota after sleeve gastrectomy, which were correlated with changes in faecal short-chain fatty acid levels. Postoperatively, G protein-coupled receptor 43 expression in the colon tissue was upregulated in both models, whereas its expression in the adipose tissue was downregulated in the diet-induced obese mouse model. CONCLUSIONS: Metabolic improvement in obese and diabetic mice after sleeve gastrectomy is associated with alterations in gut microbiota, short-chain fatty acid levels, and G protein-coupled receptor 43 expressions. SIGNIFICANCE AND IMPACT OF STUDY: Our findings reveal a possible mechanism through which sleeve gastrectomy improves obesity and diabetes via changes in bacteria producing short-chain fatty acids and G protein-coupled receptor 43.

Incidence and Predictors of Synchronous Bone Metastasis in Newly Diagnosed Differentiated Thyroid Cancer: A Real-World Population-Based Study.

BACKGROUND: Clinical and sociodemographic characteristics of differentiated thyroid cancer (DTC) patients with synchronous bone metastasis (SBM) remain unclear. This real-world study aimed to elucidate the incidence and prognosis of DTC patients with SBM using population-based data. METHODS: Data of patients with newly diagnosed DTC from 2010 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic regression analysis was utilized to identify predictors of developing SBM in patients with DTC and was further evaluated by receiver operator characteristics (ROC) analysis. Multivariable Cox regression was applied to identify prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 67,176 patients with DTC were screened from the database, with 0.36% (244/67,176) developed SBM. The age-adjusted incidence of SBM in patients with DTC was relatively stable during the study period with an average annual percentage change (AAPC) of 2.52. Multivariable logistic regression analysis recognized seven factors (older age, male gender, black race, other races, follicular histology, the American Joint Committee on Cancer (AJCC) T2, T3, T4 staging, and N1 staging) as predictors of developing SBM among the entire cohort, with the value of area under the curve (AUC) of 0.931 (95% CI: 0.915-0.947). The median survival time of DTC patients with SBM was 22 months (interquartile range, 7-47 months). The multivariable Cox regression analysis indicated multiple metastatic sites, surgical procedures, and chemotherapy as predictors for the survival of patients. CONCLUSIONS: Predictors and prognostic factors of SBM in patients with DTC were identified in this study. Patients with risk factors should be given more attention in clinical practice.

Identification of the potential roles of ring finger protein 8 in TP53-mutant breast cancer.

Breast cancer is one of the malignant tumors with the highest mortality rate. With the development of precise treatment technology for cancer, numerous molecular targets have been identified and applied in the treatment of diseases. The present study investigated the potential role of ring finger protein 8 (RNF8) in TP53-mutant breast cancer and explored its possible mechanisms of action through a combination of bioinformatics techniques and cell biology. The results revealed that significantly different genes were expressed in RNF8-knockout mice sequencing data compared with in the control group in the presence of TP53 mutations. Downregulated genes were significantly enriched in several pathways of cell proliferation and apoptosis regulation, development and transcription regulation, while upregulated genes were mainly enriched in immune response-associated signaling pathways. Therefore, the consensus genes of the major signaling pathways were further analyzed, revealing that among patients with TP53 wild-type breast cancer, the prognosis of patients with low expression levels of fibroblast growth factor receptor 1, LIM homeobox 2 and EPH receptor B2 was improved compared with that of patients with high expression levels, while among patients with TP53-mutant breast cancer, there was no significant difference in survival status. In addition, among patients with TP53-mutant breast cancer, the prognosis of patients with high BR serine/threonine kinase 1 expression was significantly improved compared with that in patients with low expression. Finally, cell biology experiments demonstrated that in TP53-mutant breast cancer cells (HCC1937), inhibition of RNF8 significantly inhibited the proliferation of TP53-mutant HCC1937 cells and promoted their apoptosis. The present findings may enrich the understanding of the role of RNF8 and indicated that RNF8 may be used as a potential molecular target in TP53-mutant breast cancer, which may lead to the development of clinical treatment strategies.

pH sensitive peptide functionalized nanoparticles for co-delivery of erlotinib and DAPT to restrict the progress of triple negative breast cancer.

Although a variety of drug delivery strategies have been designed for enhancing the treatment of Triple negative breast cancer (TNBC), combating with TNBCs is still dramatically challenged by the selection of appropriate therapeutic targets and insufficient tumor accumulation or inner penetration of chemotherapeutics. To address these issues, the classical EGFR-inhibitor, erlotinib (EB), was selected as the model drug here and PLA-based nano-platform (NP-EB) was prepared for tumor site drug delivery. Given the significant role of Notch-EGFR interplay in raising severe resistance to EGFR inhibition of EB, gamma secretase inhibitor (GSI)-DAPT was further entrapped into the core of nanoparticles to inhibit the activation of Notch signaling (NP-EB/DART). For achieving the goal of tumor targeting drug delivery, we developed a new peptide CF and decorating it on the surface of EB/DART-dual loaded nanoparticles (CF-NP-EB/DART). Such CF peptide was designed by conjugating two separated peptide CREKA, tumor-homing peptide, and F3, cell penetrating peptide, to together via a pH-sensitive hydrazone bond. By this way, the tumor unspecific property of F3 was sealed and significantly reduced the site effects. However, after the nanoparticles reach the tumor site, the pH-sensitive linkage can be broken down by the unique acidic environment of tumor, and subsequently discovered the F3 peptide to penetrate into tumor cells.

Roux-en-Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats.

BACKGROUND: Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux-en-Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram-negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. METHODS: Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham-operated group pair-fed with the RY group; and (c) a sham-operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate-dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)-1, occludin, and claudin-1 were assessed 10 weeks postoperatively. RESULTS: Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin-1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO-1, occludin, and claudin-1 expression. CONCLUSIONS: The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram-negative bacteria.

The Diffusion of Low-Energy Methyl Group on ITO Film Surface and Its Impact on Optical-Electrical Properties.

Indium tin oxide (ITO) film is one of the ideal candidates for transparent conductive cathode in methylammonium lead halide perovskite solar cells. Thus, the diffusion of methyl group in ITO film is inevitable, which could deteriorate the optical-electrical property of ITO film. In this study, ITO films with and without (100) preferred orientation were bombarded by the low-energy methyl group beam. After the bombardment, the optical-electrical property of ITO film without (100) preferred orientation deteriorated. The bombardment of methyl group had little influence on the optical-electrical property of ITO film with (100) preferred orientation. Finally, combining the crystallographic texture and chemical bond structure analysis, the diffusion mechanism of low-energy methyl group on ITO lattice and grain boundary, as well as the relation between the optical-electrical property and the diffusion of the methyl group, were discussed systematically. With the above results, ITO film with (100) preferred orientation could be an ideal candidate for transparent conductive cathode in methylammonium lead halide perovskite solar cells.

The effect of metabolic surgery on nonobese patients (BMI<30 kg/m2) with type 2 diabetes: a systematic review.

BACKGROUND: The influence of metabolic surgery on the glucose and lipid profiles of nonobese body mass index<30 kg/m2 patients with type 2 diabetes, particularly the effect ≥1 year, remains unknown. METHODS: PubMed and Ovid Embase were used. SETTING: University hospitals. RESULTS: In total, 21 studies including 921 patients were examined in this systematic review, the results of which revealed decrease in body mass index, waist circumference, fasting plasma glucose, glycosylated hemoglobin A1C, fasting C-peptide, fasting insulin, homeostasis model of assessment for insulin resistance index, triglycerides, total cholesterol, and low-density lipoprotein cholesterol. An increase in high-density lipoprotein cholesterol was also observed. The diabetes remission rates ranged from 13.3% to 90.2% according to 20 studies. The incidence of gastrointestinal bleeding ranged from 1% to 10% according to 9 studies. Four studies reported anemia after Roux-en-Y gastric bypass or one-anastomosis gastric bypass, with the incidence ranging from 8% to 33%. CONCLUSIONS: Nonobese patients can achieve improvements in weight-related indices and glucose and lipid profiles in the short and medium term after metabolic surgery; however, the complications of metabolic surgery warrant further attention.

Characterization of circulating tumor cells in newly diagnosed breast cancer.

Identification of circulating tumor cells (CTCs) by surface marker expression and ploidy analysis [immunostaining-fluorescence in situ hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90.76%) by the iFISH system. Higher CTC counts and sensitivity were observed in patients with increased tumor size burden and unfavorable hormone receptor status. Investigation of CTC subtypes based on ploidy analysis indicated that triploid CTCs constituted the majority of CTCs evaluated. While CK-positive CTCs were detected in a small cohort of patients, an overall low rate of CK expression was observed in the 18 patient samples evaluated. Of note, CK expression was rare in CTCs detected in patients with Herceptin 2 (Her2)-positive or triple-negative [estrogen receptor (ER)-, progesterone receptor (PR)- and Her2-negative], indicating that lack of ER and PR may result in promotion of epithelial-mesenchymal transition and enhancement of tumor aggression.

Modulation of the gut microbiome: a systematic review of the effect of bariatric surgery.

OBJECTIVE: Bariatric surgery is recommended for patients with obesity and type 2 diabetes. Recent evidence suggested a strong connection between gut microbiota and bariatric surgery. DESIGN: Systematic review. METHODS: The PubMed and OVID EMBASE were used, and articles concerning bariatric surgery and gut microbiota were screened. The main outcome measures were alterations of gut microbiota after bariatric surgery and correlations between gut microbiota and host metabolism. We applied the system of evidence level to evaluate the alteration of microbiota. Modulation of short-chain fatty acid and gut genetic content was also investigated. RESULTS: Totally 12 animal experiments and 9 clinical studies were included. Based on strong evidence, 4 phyla (Bacteroidetes, Fusobacteria, Verrucomicrobia and Proteobacteria) increased after surgery; within the phylum Firmicutes, Lactobacillales and Enterococcus increased; and within the phylum Proteobacteria, Gammaproteobacteria, Enterobacteriales Enterobacteriaceae and several genera and species increased. Decreased microbial groups were Firmicutes, Clostridiales, Clostridiaceae, Blautia and Dorea. However, the change in microbial diversity is still under debate. Faecalibacterium prausnitzii, Lactobacillus and Coprococcus comes are implicated in many of the outcomes, including body composition and glucose homeostasis. CONCLUSIONS: There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.

Effects of bariatric surgery on glycemic and lipid metabolism, surgical complication and quality of life in adolescents with obesity: a systematic review and meta-analysis.

BACKGROUND: Obesity in adolescents is associated with numerous health risks and co-morbidities, including type 2 diabetes and dyslipidemia. Bariatric surgery on adolescents induces weight loss, but little is known about metabolic effects of these operations. OBJECTIVE: To explore weight loss and metabolic effects of bariatric surgery on young people. SETTING: A systematic review and meta-analysis. University Hospital, China. METHODS: PubMed and EMBASE were searched for relevant studies up to July 2017. The related studies in adolescents after operation were included. RESULTS: A total of 49 studies with 3007 patients were included. The average preoperative age ranged from 13.9 to 19.9 years. Roux-en-Y gastric bypass (n = 1216), laparoscopic adjustable gastric banding (n = 1028), and laparoscopic sleeve gastrectomy (n = 665) were the most common bariatric surgeries performed. At the longest follow-up (range, 12-120 mo), bariatric surgery led to an overall 16.43 kg/m2 (95% confidence interval [CI]: 14.84-18.01) and 31% (95% CI: 28%-34%) reduction in body mass index. There were significant improvements in glycemic and lipid profiles including glycosylated hemoglobin A1C, fasting blood insulin, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, postoperatively at 12 months. The remission rate of dyslipidemia was 55% (95% CI: 34%-76%), 70% (95% CI: 55%-82%), and 95% (95% CI: 80%-100%) at 1, 3, and>5 years after surgery. Roux-en-Y gastric bypass produced better improvements than other surgical procedures. CONCLUSION: Bariatric surgery in adolescents may achieve significant weight loss, and glycemic and lipid control. Further well-designed studies with longer follow-up are warranted to provide more reliable evidence.

Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer.

Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial-mesenchymal-transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial-to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc.

Plasma olfactomedin 4 level in peripheral blood and its association with clinical features of breast cancer.

The present study aimed to investigate the expression of olfactomedin 4 (OLFM4) in plasma of patients with breast cancer and its association with diagnosis, metastasis and prognosis of breast cancer. OLFM4 gene expression level of peripheral blood plasma in 60 patients with breast cancer and 26 healthy donors was examined by ELISA. The expression of OLFM4 in tumor tissues of patients with breast cancer was evaluated by immunohistochemistry (protein expression) and reverse transcription-quantitative polymerase chain reaction (mRNA expression), respectively. Circulating tumor cells (CTCs) were detected in a certain set of patients. The expression of OLFM4 in plasma of the overall healthy people was higher compared with patients with breast cancer. The plasma OLFM4 level in patients with breast cancer was consistent with the expression of OLFM4 protein in tumor tissues (R2=1), indicating that the level of plasma OLFM4 expression may represent the expression of OLFM4 in breast cancer tissues. The plasma OLFM4 level in patients with histological grade I was significantly lower compared with grade III (P<0.05). Breast cancer patients with positive CTC were associated with low level of plasma OLFM4. These results suggest that low OLFM4 expression in plasma or tissue specimens of breast cancer patients is more likely to represent low histological differentiation and decreased invasive/metastatic capabilities. Taken together, plasma OLFM4 level may be considered as a biomarker for diagnosis and prognosis of breast cancer for cases where there are difficulties in obtaining tumor tissue samples.

Gut microbiota after Roux-en-Y gastric bypass and sleeve gastrectomy in a diabetic rat model: Increased diversity and associations of discriminant genera with metabolic changes.

Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham-operated with pair-fed as RYGB; sham-operated fed ad libitum; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham-operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance.

Modulation of the number and functions of endothelial progenitor cells by interleukin 1ß in the peripheral blood of pigs: involvement of p38 mitogen-activated protein kinase signaling in vitro.

BACKGROUND: Endothelial progenitor cells (EPCs) have therapeutic potential for the treatment of organ ischemia following trauma or sepsis, frequently associated with inflammatory conditions. We aimed to investigate the effects of interleukin 1ß (IL-1ß) on the properties of EPCs and explore its possible relationship with p38 mitogen-activated protein kinase (MAPK). METHODS: EPCs were isolated from peripheral blood of a porcine model and were characterized. Effects of IL-1ß on cell number, proliferation, migration, adhesion, and angiogenic function of EPCs were evaluated in a time- and dose-dependent manner. The activity of p38 MAPK in EPCs was measured by Western blot. Moreover, the effects of SB203580, a specific p38 MAPK inhibitor, on levels of p38 MAPK phosphorylation and the number and functions of EPCs under IL-1ß conditions were examined. RESULTS: Incubation of EPCs with IL-1ß (5 ng/mL) for 5 days and with IL-1ß (0.05-50 ng/mL) for 48 hours induced a significant reduction in EPC numbers and proliferation, respectively (p < 0.01 vs. control cells). The capacities for migration, adhesion, and angiogenic function of EPCs were also reduced in a time- and dose-dependent manner. IL-1ß induced dose- and time-dependent activation of p38 MAPK in EPCs. Moreover, inhibition of p38 MAPK by SB203580 significantly increased the total number of EPCs by twofold as compared with the IL-1ß-alone group (p < 0.01) and blocked the ability of IL-1ß to impair the functional response of EPCs. CONCLUSION: These results demonstrate that there is a negative cause-effect relationship between IL-1ß and EPCs. Thus, IL-1ß inhibits EPC proliferation, migration, adhesion, and tube formation by a mechanism, which involves p38 MAPK signaling in regulating the number and functions of EPCs in vitro.

Late morbidity associated with a tumour-negative sentinel lymph node biopsy in primary breast cancer patients: a systematic review.

AIMS: To evaluate the relationship between late morbidity (i.e. > or =6 months) and a tumour-negative sentinel lymph node biopsy (SLNB) in primary breast cancer patients by using a systematic review approach, and to identify the predictors of late morbidity. METHODS: We performed a systematic review of the literature for studies concerning the late morbidity of patients who had undergone SLNB alone or SLNB followed by ALND when SLN metastases were found. A literature search over the last 16 years (1993-2008) was performed in the databases MEDLINE and EMBASE. The methodological quality of the selected studies was assessed according to a list of predefined criteria. The data of assessment and predictors of late morbidity were collected. RESULTS: We identified a total of 32 papers reporting 27 independent cohort studies, of which 17 were high quality studies and were further analysed in this review. There was a great variation in the prevalence of pain (7.5-36%), impairment of range of motion (0.0-31.0%), oedema (0.0-14.0%), decreased strength (11.0-19.0%) and sensory disorders (1.0-66.0%). Factors such as time after surgery and young age were strong predictors of late morbidity. Breast surgery, radiation to axilla, tumour location, body mass index (BMI) and two-step procedure, especially lymph mapping techniques, could also predict the late morbidity to different extents. CONCLUSIONS: SLNB-associated late morbidity, even with a low prevalence, remains a clinical problem which cannot be neglected in primary breast cancer patients. Time after surgery and young age are the important predictors for late morbidity in primary breast cancer patients after SLNB; breast surgery, radiation to axilla, tumour location, BMI and two-step procedure also have limited prognostic value.