Early Pregnancy (≤ 12 Months) After Bariatric Surgery: Does It Really Influence Maternal and Perinatal Outcomes?

BACKGROUND: Current guidelines do not recommend pregnancy within 12 months after bariatric surgery; however, there is a lack of consensus and scientific evidence to support this. The study is to evaluate the influence of early pregnancy (≤ 12 months) after bariatric surgery on maternal and perinatal outcomes. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for all studies comparing maternal and perinatal outcomes for surgery-to-conception intervals of ≤ 12 months and > 12 months. RESULTS: A total of 13 studies were included. The pooled results showed that early pregnancy was associated with insufficient gestational weight gain (WMD: - 6.04, 95%CI [- 7.39, - 4.15], p < 0.01). No significant difference was found in gestational diabetes, gestational hypertension, preeclampsia, caesarean section, and postpartum hemorrhage between surgery-to-conception intervals of ≤ 12 months and > 12 months. There were also no significant differences between the two groups regarding the neonatal outcomes, including preterm birth, small for gestational age, large for gestational age, macrosomia, birth defect, neonatal intensive care unit admission, and Apgar score ≤ 7 within 5 min. CONCLUSIONS: Early pregnancy (≤ 12 months) after bariatric surgery seems have no significant adverse effects on maternal and perinatal outcomes, with the exception of insufficient gestational weight gain. Pregnancy after bariatric surgery should be personalized based on the individual patient. Further studies on larger cohorts are warranted.

Preoperative reflux or regurgitation symptoms are independent predictors of postoperative nausea and vomiting (PONV) in patients undergoing bariatric surgery: a propensity score matching analysis.

BACKGROUND: Postoperative nausea and vomiting (PONV) is common side effect after gastrointestinal surgery. It causses discomfort, increase risk of incision disruption, bleeding and airway blockage. This study aimed to investigate the incidence and severity of PONV and determine whether preoperative reflux or regurgitation symptoms influence PONV in patients undergoing bariatric surgery. METHODS: Patients with obesity underwent laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in our center between January 2016 and December 2018 were divided into PONV and NoPONV group and analyzed retrospectively. PONV and postoperative pain visual analogue scale (VAS) were analyzed after surgery. A 1:1 propensity score matching (PSM) method was performed, and multivariable logistic regression analyses were used to identify predictors for PONV. RESULTS: There were 483 patients enrolled, with a mean age of 30.19 ± 9.96 years, and 134 pairs of matched patients were selected from PONV group and NoPONV group after PSM. PONV occurred in 288 (59.6%) patients after bariatric surgery (77.4% after LSG vs 21.5% after LRYGB, p < 0.001). In PONV group, 210 (72.9%) were female, preoperative reflux or regurgitation symptoms were 128 (33.6%). Multivariable analysis found that preoperative reflux or regurgitation symptoms were independent risk factors for PONV after LSG, with an OR of 2.78 (95% CI: 1.12-6.93, p = 0.028). CONCLUSIONS: Incidence of PONV after bariatric surgery is high. For the first time, this study valued preoperative reflux or regurgitation symptoms as risk factors that may promote PONV after bariatric surgery. Patients with preoperative symptoms undergoing LSG have a higher risk of PONV, so these patients should be carefully evaluated for the feasibility of LSG before surgery.

Effects of bariatric surgery on testosterone level and sexual function in men with obesity: A retrospective study.

Introduction: Bariatric surgeries induce well-documented weight loss and resolve obesity comorbidities. Sexual function is one of the aspects of life quality and may benefit from surgery. Few studies have revealed the impact of bariatric surgeries on sexual function in Chinese men with obesity. Methods: This is a retrospective cohort study of patients undergoing bariatric surgery [laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB)]. Data were collected between September 2017 and February 2022. The International Index of Erectile Function (IIEF) questionnaire was used to evaluate erectile function, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Sex hormones and other blood tests were evaluated before and at least 1 year after the surgery. Results: Fifty-nine Chinese male patients completed the IIEF questionnaire. The multivariate logistic regression analysis revealed that body mass index (BMI) was the single independent risk factor of the severity of erectile dysfunction (ED). Preoperative testosterone levels had negative correlations with BMI and waist circumference. Thirty-seven patients completed the postoperative questionnaire with a mean follow-up of 23.2 months. Conclusion: BMI and waist circumference were negatively correlated with testosterone levels. BMI was an independent risk factor for the severity of ED. LSG and LRYGB led to positive and sustained improvement in sexual function of men with obesity. The two procedures had a comparable effect, more subjects being needed. Sex hormone levels also could be reversible. However, more weight loss did not predict a positive change in sexual function. A greater BMI loss might predict a greater increase in testosterone.

An immune-related signature that to improve prognosis prediction of breast cancer.

Although the classic molecular subtype of breast cancer (BRCA) has been widely used in clinical diagnosis, as a highly heterogeneous malignant tumor, the classic scheme is not enough to accurately predict the prognosis of breast cancer patients. Immune cells in the tumor microenvironment (TME) are thought to play a paramount role in tumor development and driving poor prognosis. In this study, we aimed to develop a TME-associated, immune-related signature to improve prognosis prediction of BRCA. BRCA_OURS enriched transcriptomic RNA sequencing (RNA-seq) of tumor tissue was acquired from 43 breast cancer patients before any treatment. On the immune gene profiles of 43 patients from BRCA_OURS and 932 BRCA patients from The Cancer Genome Atlas (TCGA), we identified a robust immune-related signature including one positive coefficients gene (IL-10) and other 9 genes (C14orf79, C1orf168, C1orf226, CELSR2, FABP7, FGFBP1, KLRB1, PLEKHO1, and RAC2), of which the negative coefficients suggesting higher expression were correlated with better prognosis. Based on the expression of these genes, patients were grouped into the high- and low-risk group with significant overall survival (OS) (P<0.0001). The high-risk group was likely to have inferior outcomes related to several important cancer-associated pathways, including mobilizing more Golgi vesicle-mediated transport and intensive DNA double-strand breaking, which are closely related to the infiltration of immune cells and holds the key for further growing and metastasizing. Collectively, our results highlight that the immunological value within BRCA is an essential determinant of prognostic factor. Our signature may provide an effective risk stratification tool for clinical prognosis assessment of patients with BRCA.

A high-risk luminal A dominant breast cancer subtype with increased mobility.

PURPOSE: Breast cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast cancer subtype stratification. METHODS: We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database. RESULTS: The samples were gathered into three clusters following implementation of the t-SNE and DBSCAN algorithms and were categorized as 'hallmark-tsne' subtypes. Here, we identified a high-risk luminal A dominant breast cancer subtype (C3) that displayed increased motility, cancer stem cell-like features, a higher expression of hormone/luminal-related genes, a lower expression of proliferation-related genes and immune dysfunction. With regard to immune dysfunction, we observed that the motility-increased C3 subtype exhibited high granulocyte colony stimulating factor (G-CSF) expression accompanied by neutrophil aggregation. Cancer cells that produce high levels of G-CSF can stimulate neutrophils to form neutrophil extracellular traps, which promote cancer cell migration. This finding sheds light on one potential explanation for why the C3 subtype correlates with poor prognosis. CONCLUSIONS: The hallmark-tsne subtypes confirmed again that even the luminal A subtype is heterogeneous and can be further subdivided. The biological processes and immune heterogeneity of breast cancer must be understood to facilitate the improvement of clinical treatments.

Single nucleotide variant profiles of viable single circulating tumour cells reveal CTC behaviours in breast cancer.

Circulating tumour cell (CTC) behaviours are distinct from those of bulk tissues. Thus, treatments to eliminate CTCs differ from the regimens followed to reduce the primary tumour and its metastases. Accordingly, comprehensively deciphering the single nucleotide variant (SNV) profiles in CTCs, which partially determine CTC behaviours, is a priority. Using viable CTCs isolated with the oHSV1­hTERT­GFP virus coupled with fluorescence­activated cell sorting (FACS), the whole genome was amplified using the multiple annealing and looping­based amplification cycle (MALBAC) method. CTC behaviours were evaluated using the SNVs found to be recurrently mutated in different cells (termed CTC­shared SNVs). Analysis of the sequencing data of 11 CTCs from 8 patients demonstrated that SNVs accumulated sporadically among CTCs and their matched primary tumours (22 co­occurring mutated genes were identified in the exomes of CTCs and their matched primary tissues and metastases), and 394 SNVs were shared by at least two CTCs. Mutated APC and LRP1B genes co­occurred in CTC­shared and bulk­tissue SNVs. Additionally, the breast­originating identity of the CTC­shared SNVs was verified, and they demonstrated the following CTC behaviours: i) intravasation competency; ii) increased migration or motility; iii) enhanced cell­cell interactions; iv) variation in energy metabolism; v) an activated platelet or coagulation system; and vi) dysfunctional mitosis. These results demonstrated that it is feasible to capture and amplify the genomes of single CTCs using the described pipeline. CTC­shared SNVs are a potential signature for identifying the origin of the primary tumour in a liquid biopsy. Furthermore, CTCs demonstrated some behaviours that are unique from those of bulk tissues. Therefore, therapies to eradicate these precursors of metastasis may differ from the existing traditional regimens.

Breast Cancer Disparities: A Multicenter Comparison of Tumor Diagnosis, Characteristics, and Surgical Treatment in China and the U.S.

BACKGROUND AND OBJECTIVE: Incidence of and mortality rates for breast cancer continue to rise in the People's Republic of China. The purpose of this study was to analyze differences in characteristics of breast malignancies between China and the U.S. METHODS: Data from 384,262 breast cancer patients registered in the U.S. Surveillance, Epidemiology, and End Results (SEER) program from 2000 to 2010 were compared with 4,211 Chinese breast cancer patients registered in a Chinese database from 1999 to 2008. Outcomes included age, race, histology, tumor and node staging, laterality, surgical treatment method, and reconstruction. The Pearson chi-square and Fisher's exact tests were used to compare rates. RESULTS: Infiltrating ductal carcinoma was the most common type of malignancy in the U.S. and China. The mean number of positive lymph nodes was higher in China (2.59 vs. 1.31, p < .001). Stage at diagnosis was higher in China (stage IIA vs. I, p < .001). Mean size of tumor at diagnosis was higher in China (32.63 vs. 21.57 mm). Mean age at diagnosis was lower in China (48.28 vs. 61.29 years, p < .001). Moreover, 2.0% of U.S. women underwent radical mastectomy compared with 12.5% in China, and 0.02% in China underwent reconstructive surgery. CONCLUSION: Chinese women were diagnosed at younger ages with higher stage and larger tumors and underwent more aggressive surgical treatment. Prospective trials should be conducted to address screening, surgical, and tumor discrepancies between China and the U.S. IMPLICATIONS FOR PRACTICE: Breast cancer patients in China are diagnosed at later stages than those in America, which might contribute to different clinical management and lower 5-year survival rate. This phenomenon suggests that an earlier detection and treatment program should be widely implemented in China. By comparing the characteristics of Chinese and Chinese-American patients, we found significant differences in tumor size, lymph nodes metastasis, and age at diagnosis. These consequences indicated that patients with similar genetic backgrounds may have different prognoses due to the influence of environment and social economic determinates.

Trends in Radical Surgical Treatment Methods for Breast Malignancies in China: A Multicenter 10-Year Retrospective Study.

BACKGROUND: Incidence rates of breast cancer continue to rise in the People's Republic of China. The purpose of this study was to describe Chinese trends in radical surgical modalities and influential imaging and demographic factors for breast malignancies. MATERIALS AND METHODS: This study was a hospital-based, multicenter, 10-year (1999-2008), retrospective study. Descriptive statistical tests were used to illustrate information regarding radical surgical trends for the treatment of breast malignancies. Chi-square tests were used to assess effect of demographic factors in addition to imaging and pathological data on the specific surgical method. RESULTS: A total of 4,211 patients were enrolled in the survey. Among them, 3,335 patients with stage 0 to stage III disease undergoing mastectomy or breast-conserving surgery (BCS) were included in the final analysis. The rate of BCS increased from 1.53% in 1999 to 11.88% in 2008. The rate of mastectomy declined over this time period, from 98.47% in 1999 to 88.12% in 2008, with increasing use of diagnostic imaging methods and pathological biopsies. A significantly greater percentage of patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy. CONCLUSION: Rates of mastectomy in China remain elevated due to diagnosis at higher stages; however, because of increased use of diagnostic imaging, improvement of biopsy methods, and patient education, rates of less invasive lumpectomy are increasing and rates of mastectomy have decreased in China. IMPLICATIONS FOR PRACTICE: In this study, 4,211 cases were collected from 1999 to 2008 through a multicenter retrospective study of varying geographic and socioeconomic areas to illustrate trends of surgeries in the People's Republic of China. The correlations between demographic and tumor characteristics and among methods of surgical treatment were explored. This study shows that the rate of breast-conserving surgery (BCS) increased and the rate of mastectomy declined over this time period with increasing use of diagnostic imaging methods and pathological biopsies. Patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy in China.

The safety parameters of the study on intraductal cytotoxic agent delivery to the breast before mastectomy.

BACKGROUND: Intraductal administration of cytotoxic agents has been shown to inhibit the development of breast cancer in animal models. The object of this study was to demonstrate the safety of intraductal delivery cytotoxic agents in patients prior to mastectomy. This method is hopeful to be developed as a chemoprevention approach in patients with pre-malignant or non-invasive ductal lesions to prevent breast cancer which will be further developed. METHODS: TWO DRUGS, PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) AND CARBOPLATIN WERE ADMINISTERED AT THREE DOSE LEVELS (PLD: 10, 20, 50 mg and carboplatin 60, 120, 300 mg). There were five subjects in each group with 15 subjects treated with each drug once. Venous blood samples were obtained for pharmacokinetic analysis. The breast was removed surgically 2-5 days post administration and the treated ducts were marked to enable identification on pathological evaluation. RESULTS: Intraductal administration was generally well-tolerated with mild, transient breast discomfort. In the carboplatin arm, three women at the 300 mg dose experienced mild nausea and vomiting. In the PLD arm most women had mild erythema and swelling of the breast over the 72 hours following the drug administration. Patients receiving the 50 mg dose experienced local erythema until the time of surgery. Pharmacokinetic analysis showed that carboplatin rapidly entered systemic circulation with an early peak time (Tmax ~30 min) with a corresponding plasma ultrafiltrate area under the curve (AUC) consistent with the Calvert Formula using estimated glomerular filtration rate (GFR). Total plasma doxorubicin had delayed peak concentration times (Tmax >48 hours) with a linear dose response and peak concentrations substantially lower than expected from equivalent intravenous injection dosing. No doxorubicinol metabolite was detected in the plasma. CONCLUSIONS: This study demonstrates that cytotoxic drugs can be safely administered into breast ducts with minimal toxicity.

A feasibility study of the intraductal administration of chemotherapy.

Preclinical data have shown the potential of the intraductal administration of chemotherapy for breast cancer prevention. Direct translation of this work has been stymied by the anatomical differences between rodents (one duct per teat) and women (5-9 ductal systems per breast). The objective of this phase I study was to show the safety and feasibility of intraductal administration of chemotherapy drugs into multiple ducts within one breast in women awaiting mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in this dose escalation study conducted at a single center in Beijing, China. Under local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated liposomal doxorubicin (PLD), was administered into five to eight ducts at three dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed after a delay. Pathologic analysis showed marked effects on breast duct epithelium in ducts treated with either drug compared with untreated ducts. The study investigators had no difficulty in identifying or cannulating ducts except in one case with a central cancer with subareolar involvement. This study shows the safety and feasibility of intraductal administration of chemotherapy into multiple ducts for the purpose of breast cancer prevention. This is an important step toward implementation of this strategy as a "chemical mastectomy", where the potential for carcinogenesis in the ductal epithelium is eliminated pharmacologically, locally, and without the need for surgery.

Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer.

BACKGROUND: Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy. METHODS: One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods. RESULTS: Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs. CONCLUSION: GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.