Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival.

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

Longitudinal, Long-Term Comparison of Single- versus Multipoint Upper Limb Circumference Periodical Measurements as a Tool to Predict Persistent Lymphedema in Women Treated Surgically for Breast Cancer: An Optimized Strategy to Early Diagnose Lymphedema and Avoid Permanent Sequelae in Breast Cancer Survivors.

PURPOSE: We aim to evaluate whether upper limb (UL) circumference (ULC) and UL swelling sensation (ULSS) performed shortly after surgery or later on during follow-up can predict long-term/persistent forms of lymphedema in women who underwent surgery for breast cancer. PATIENTS AND METHODS: Eighty-five women completed at least 24 months of follow-up. At each follow-up visit (1, 3, 6, 12, and 24 months after surgery), patients were tested for lymphedema using ULC and ULSS. Two different approaches to ULC were compared: (1) a "positive" lymphedema diagnosis if a difference ≥ 2 cm between the affected and contralateral UL was detected in at least two contiguous measurement points (MPs) and (2) a "positive" result if just one MP ≥ 2 cm. Patients were also questioned about their perception of weight, swelling, and/or tension (ULSS). The gold standard for long-term lymphedema was a water displacement difference between the UL ≥ 200 mL 24 months after surgery (ULWD). RESULTS: Twenty-four months after surgery, 19 (22.4%) women were diagnosed with long-term lymphedema. Using 24-month data, comparison of log-likelihoods denoted a clear superiority of the ULC approach 1 compared with 2 for the diagnosis of long-term lymphedema (p < 0.001). Using approach 1, the best prediction of a woman developing long-term lymphedema if she had a positive ULC in the follow-up was obtained at 6 months after surgery (posterior probability of 60%). CONCLUSIONS: Our study reveals that performing ULC 6 months after surgery, regarding as "positive" only women with a difference ≥ 2 cm at two contiguous MPs, is the best strategy to identify women at increased risk of later developing permanent forms of lymphedema.

Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial.

OBJECTIVE: The present analysis determined the disease free survival (DFS) and overall survival (OS) at up to 14 years of follow-up in women who participated in our previous phase 3 randomized controlled clinical trial, in which women with stage IIIB squamous cervical cancer received either cisplatin plus RT or RT alone for treatment. The first study showed that the addition of cisplatin to RT offered a significant benefit in DFS, but not in OS. METHODS: The present analysis examined DFS and OS in 146 women from the original cohort (72 patients in the CRT arm and 74 patients in the RT-only arm) with follow-up of up to 14 years. RESULTS: Longer term follow-up showed that treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only. Patients who received RT alone had significantly worse OS (HR, 1.88; 95% CI, 1.09-3.24) and DFS (HR, 1.82; 95% CI, 1.07-3.08) compared with patients who received CRT. The multivariate analyses also showed that the patients with baseline Karnofsky performance status (KPS) <90% showed significantly worse OS (HR, 3.11; 95% CI, 1.78-5.43), as did those with hemoglobin <10 mg/dL (HR, 4.32; 95% CI, 2.23-8.36). Patients with baseline KPS < 90% showed significantly worse DFS (HR, 2.83; 95% CI, 1.60-5.01), as did those with hemoglobin <10 mg/dL (HR, 4.16; 95% CI, 2.17-7.95). CONCLUSIONS: For stage IIIB cervical cancer, treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only.

Physical and functional well-being and symptoms of ovarian cancer in women undergoing first-line of chemotherapy: a one-year follow-up.

PURPOSE: Clinicopathological features and chemotherapy can influence the quality of life (QOL), women with ovarian cancer. This study aimed to evaluate the physical and functional well-being, and ovarian cancer-specific effects scores reported from QOL questionnaire among women with ovarian cancer at the time of in their initial diagnosis and access the scores trajectory of women receiving neoadjuvant and adjuvant chemotherapy. METHODS: This prospective study used cross-sectional analysis at baseline and longitudinal analysis from baseline to 12-month post-chemotherapy. QOL was evaluated at the baseline, at sixth cycle and 12-month post-chemotherapy using FACT-O questionnaire. Clinicopathological features and chemotherapy regime were evaluated and tested for associations with QOL measures. RESULTS: Of the 38 women enrolled in this study, 27 (80.1%) completed the questionnaire for 12 months. The multivariate linear regression results suggest, at the baseline, women with advance stage and presence of post-surgery residual disease showed lower scores in physical and functional well-being, ovarian cancer-specific effects, and FACT-O TOI domains (p < 0.05). Longitudinal analysis spanning over 12 months showed an improvement in mean physical well-being, functional well-being, and ovarian cancer-specific effects scores, independent of chemotherapy received (p < 0.05). CONCLUSIONS: At the baseline, the clinicopathological features such as stage, presence of post-surgery residual disease, and type of chemotherapy correlated with on QOL scores. At one-year follow-up, women who underwent chemotherapy showed improvement in QOL regardless of the type of chemotherapy they received. Future prospective study with a larger group is recommended.

Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed). RESULTS: We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I2  = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I2  = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I2  = 0%, P = .84). CONCLUSIONS: Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.

Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer.

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II - versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II - versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

Multicenter Study Using Desorption-Electrospray-Ionization-Mass-Spectrometry Imaging for Breast-Cancer Diagnosis.

The histological and molecular subtypes of breast cancer demand distinct therapeutic approaches. Invasive ductal carcinoma (IDC) is subtyped according to estrogen-receptor (ER), progesterone-receptor (PR), and HER2 status, among other markers. Desorption-electrospray-ionization-mass-spectrometry imaging (DESI-MSI) is an ambient-ionization MS technique that has been previously used to diagnose IDC. Aiming to investigate the robustness of ambient-ionization MS for IDC diagnosis and subtyping over diverse patient populations and interlaboratory use, we report a multicenter study using DESI-MSI to analyze samples from 103 patients independently analyzed in the United States and Brazil. The lipid profiles of IDC and normal breast tissues were consistent across different patient races and were unrelated to country of sample collection. Similar experimental parameters used in both laboratories yielded consistent mass-spectral data in mass-to-charge ratios ( m/ z) above 700, where complex lipids are observed. Statistical classifiers built using data acquired in the United States yielded 97.6% sensitivity, 96.7% specificity, and 97.6% accuracy for cancer diagnosis. Equivalent performance was observed for the intralaboratory validation set (99.2% accuracy) and, most remarkably, for the interlaboratory validation set independently acquired in Brazil (95.3% accuracy). Separate classification models built for ER and PR statuses as well as the status of their combined hormone receptor (HR) provided predictive accuracies (>89.0%), although low classification accuracies were achieved for HER2 status. Altogether, our multicenter study demonstrates that DESI-MSI is a robust and reproducible technology for rapid breast-cancer-tissue diagnosis and therefore is of value for clinical use.

Collagen analysis by second-harmonic generation microscopy predicts outcome of luminal breast cancer.

Second-harmonic generation microscopy represents an important tool to evaluate extracellular matrix collagen structure, which undergoes changes during cancer progression. Thus, it is potentially relevant to assess breast cancer development. We propose the use of second-harmonic generation images of tumor stroma selected on hematoxylin and eosin-stained slides to evaluate the prognostic value of collagen fibers analyses in peri and intratumoral areas in patients diagnosed with invasive ductal breast carcinoma. Quantitative analyses of collagen parameters were performed using ImageJ software. These parameters presented significantly higher values in peri than in intratumoral areas. Higher intratumoral collagen uniformity was associated with high pathological stages and with the presence of axillary lymph node metastasis. In patients with immunohistochemistry-based luminal subtype, higher intratumoral collagen uniformity and quantity were independently associated with poorer relapse-free and overall survival, respectively. A multivariate response recursive partitioning model determined 12.857 and 11.894 as the best cut-offs for intratumoral collagen quantity and uniformity, respectively. These values have shown high sensitivity and specificity to differentiate distinct outcomes. Values of intratumoral collagen quantity and uniformity exceeding the cut-offs were strongly associated with poorer relapse-free and overall survival. Our findings support a promising prognostic value of quantitative evaluation of intratumoral collagen by second-harmonic generation imaging mainly in the luminal subtype breast cancer.

BRCA1, Ki67, and ß-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma.

OBJECTIVE: The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and ß-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included. BRCA1, Ki67, and ß-catenin expression was assessed using tissue microarray-based immunohistochemistry. RESULTS: Women with HGSOC were significantly more likely to have advanced-stage disease (P < 0.001), higher CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher rates of disease progression and recurrence (P = 0.001). The percentage of women with HGSOC whose tumors expressed Ki67 was significantly higher compared with women with LGSOC (P < 0.001). The expression of BRCA1 and ß-catenin did not differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The clinicopathological features and the response to platinum-based chemotherapy did not differ according to the BRCA1, Ki67, and ß-catenin expression in either group. In HGSOC, only International Federation of Gynecology and Obstetrics stage was independently associated with poor survival (PFS and OS). CONCLUSIONS: Ki67 expression was significantly higher in HGSOC. BRCA1 and ß-catenin expression did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and ß-catenin expression was neither related to clinicopathological features, response to platinum-based chemotherapy, nor survival. Only International Federation of Gynecology and Obstetrics stage remained associated with poor survival in women with HGSOC.

Power Doppler Ultrasonography and Shear Wave Elastography as Complementary Imaging Methods for Suspected Local Breast Cancer Recurrence.

OBJECTIVES: To prospectively investigate the diagnostic accuracy and clinical consequences of power Doppler morphologic criteria and shear wave elastography (SWE) as complementary imaging methods for evaluation of suspected local breast cancer recurrence in the ipsilateral breast or chest wall. METHODS: Thirty-two breast masses with a suspicion of local breast cancer recurrence on B-mode ultrasonography underwent complementary power Doppler and SWE evaluations. Power Doppler morphologic criteria were classified as avascular, hypovascular, or hypervascular. Shear wave elastography was classified according to a 5-point scale (SWE score) and SWE maximum elasticity. Diagnostic accuracy was assessed by the sensitivity, specificity, and area under the curve. A decision curve analysis assessed clinical consequences of each method. The reference standard for diagnosis was defined as core needle or excisional biopsy. RESULTS: Histopathologic examinations revealed 9 (28.2%) benign and 23 (71.8%) malignant cases. Power Doppler ultrasonography (US) had sensitivity of 34.8% (95% confidence interval [CI], 6.6%-62.9%) and specificity of 45.4% (95% CI, 19.3%-71.5%). The SWE score (≥3) had sensitivity of 87.0% (95% CI, 66.4%-97.2%) and specificity of 44.4% (95% CI, 13.7%-78.8%). The SWE maximum elasticity (velocity > 6.5cm/s) had sensitivity of 87% (95% CI, 66.4%-97.2%) and specificity of 77.8% (95% CI, 40.0% to 97.2%). The areas under the curves for the SWE score and SWE maximum elasticity were 0.71 (95% CI, 0.53-0.87) and 0.82 (95% CI, 0.64-0.93), respectively (P = .32). CONCLUSIONS: Power Doppler US is unsuitable for discrimination between local breast cancer recurrence and fibrosis. Although the SWE score and SWE maximum elasticity can make this discrimination, the use of these methods to determine biopsy may lead to poorer clinical outcomes than the current practice of performing biopsies of all suspicious masses.

Development of a Ki-67-based clinical trial assay for neoadjuvant endocrine therapy response monitoring in breast cancer.

PURPOSE: The recent publication of the ACOSOG Z1031 trial results demonstrated that Ki-67 proliferation marker-based neoadjuvant endocrine therapy response monitoring could be used for tailoring the use of adjuvant chemotherapy in ER+HER2-negative breast cancer patients. In this paper, we describe the development of the Ki-67 clinical trial assay used for this study. METHODS: Ki-67 assay assessment focused on reproducing a 2.7% Ki-67 cut-point (CP) required for calculating the Preoperative Endocrine Prognostic Index and a 10% CP for poor endocrine therapy response identification within the first month of neoadjuvant endocrine treatment. Image analysis was assessed to increase the efficiency of the scoring process. Clinical outcome concordance for two independent Ki-67 scores was the primary performance metric. RESULTS: Discordant scores led to a triage approach where cases with complex histological features that software algorithms could not resolve were flagged for visual point counting (17%). The final Ki-67 scoring approach was run on T1/2 N0 cases from the P024 and POL trials (N = 58). The percent positive agreement for the 2.7% CP was 87.5% (95% CI 61.7-98.5%); percent negative agreement 88.9% (95% CI: 65.3-98.6%). Minor discordance did not affect the ability to predict similar relapse-free outcomes (Log-Rank P = 0.044 and P = 0.055). The data for the 10% early triage CP in the POL trial were similar (N = 66), the percentage positive agreement was 100%, and percent negative agreement 93.55% (95% CI: 78.58-99.21%). The independent survival predictions were concordant (Log-rank P = 0.0001 and P = 0.01). CONCLUSIONS: We have developed an efficient and reproducible Ki-67 scoring system that was approved by the Clinical Trials Evaluation Program for NCI-supported neoadjuvant endocrine therapy trials. Using the methodology described here, investigators are able to identify a subgroup of patients with ER+HER2-negative breast cancer that can be safely managed without the need of adjuvant chemotherapy.

Manual Lymphatic Drainage and Active Exercise Effects on Lymphatic Function Do Not Translate Into Morbidities in Women Who Underwent Breast Cancer Surgery.

OBJECTIVE: To evaluate manual lymphatic drainage (MLD) and active exercise effects on lymphatic alterations of the upper limb (UL), range of motion (ROM) of shoulder, and scar complications after breast cancer surgery. DESIGN: Clinical trial. SETTING: Health care center. PARTICIPANTS: Women (N=105) undergoing radical breast cancer surgery who were matched for staging, age, and body mass index. INTERVENTIONS: Women (n=52) were submitted to MLD and 53 to active exercises for UL for 1 month and followed up. MAIN OUTCOME MEASURES: Shoulder ROM, surgical wound inspection and palpation, UL circumference measurements, and lymphoscintigraphy were performed in preoperative and postoperative periods. RESULTS: There was no significant difference between groups with regard to wound healing complications, ROM, and UL circumferences. After surgery, 25 (48.1%) of the MLD group and 19 (35.8%) of the active exercise group showed worsening in radiopharmaceutical uptake velocity, whereas 9 (17.3%) of the MLD group and 11 (20.8%) of the active exercise group showed improved velocity (P=.445). With regard to uptake intensity, 27 (51.9%) of the MLD group and 21 (39.6%) of the active exercise group showed worsening whereas 7 (13.5%) of the MLD group and 7 (13.2%) of the active exercise group showed some improvement (P=.391). The presence of collateral circulation was similar in both groups at both time points evaluated. The active exercise group had a significant increase in postoperative liver absorption (P=.005), and the MLD group had a significant increase in postoperative dermal backflow (P=.024). CONCLUSIONS: MLD and active exercise effects are equivalent with regard to morbidity. Minor changes in lymphatic function associated with either MLD or active exercises were not related to patients' symptoms or signs.

Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?

AIM: To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS: Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared. RESULTS: Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%. CONCLUSION: CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%.

Performance of the Risk of Malignancy Index for Discriminating Malignant Tumors in Women With Adnexal Masses.

OBJECTIVES: We examined the performance of 4 risk of malignancy index (RMI) variants in a medium-resource gynecologic cancer center. METHODS: A total of 158 women referred for adnexal masses were evaluated before surgery by the 4 RMI variants. Physicians with varied experience in ultrasound assessment of adnexal masses performed ultrasound examinations. We compared the performance of the 4 RMI variants using receiver operating characteristic curve analyses followed by calculation of sensitivity, specificity, and positive and negative likelihood ratios using the pathologic diagnosis of the masses as the reference standard. RESULTS: Among the 158 women with adnexal masses included in this study, 51 (32%) had malignant tumors; 26 (51%) of them were stage I. All RMI variants performed similarly (accuracy range, 74%-83%), regardless of menopausal status. Considering all women included, the positive likelihood ratios of the 4 RMI variants ranged from 3.52 to 4.41. In subset analyses, all RMI variants had decreased sensitivity for stage I malignant tumors and for those of nonepithelial histologic types. CONCLUSIONS: The 4 RMI variants performed acceptably in a medium-resource setting where ultrasound examiners were physicians with varied experience. This finding indicates a good tradeoff between performance and feasibility, since ultrasound RMI protocols are of low complexity.

Omentum for Mammary Disorders: A 30-Year Systematic Review.

PURPOSE: Although the safety of applying omentum to the female breast for total breast reconstruction is controversial, it has recently been used to treat certain mammary disorders as well. A systematic review was therefore conducted to analyze and establish the suitability and safety of applying omentum to the breast. METHODS: Covereing the interval from January 1984 to December 2013, we performed searches in MEDLINE, Embase, SciELO, and Google-Scholar for original articles describing the applicability of greater omentum to the breast and its clinical complications. RESULTS: Sixty observational articles with 985 women were chosen. The main clinical indications were total breast reconstruction after mastectomy due to breast cancer (45 studies), radiation damage (23 studies), and congenital Poland syndrome (4 studies). Altogether, 273 complications were identified among the 985 women treated. The most frequent was flap necrosis (26.74 %). The most serious was injury to the digestive system (1.10 %). There was a 35.48 % incidence of local breast cancer recurrence in eight observational studies on oncological risk. Seven of the eight included only women with advanced cancer. One of these studies reported the incidence and relapse time predominantly according to the primary tumor size. CONCLUSIONS: Although the oncological risk remains unclear, there was a high volume of complications that affected the digestive system. These findings suggest that omentum has well established applicability, but only for total breast reconstruction of huge defects, where muscular/myocutaneous or perforator flaps may be unsuitable.

Surgical treatment of microinvasive cervical cancer: analysis of pathologic features with implications on radicality.

OBJECTIVES: To evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens. METHODS: Women with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions. RESULTS: Fifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30-67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths. CONCLUSIONS: Patients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.

A portrait of single and multiple HPV type infections in Brazilian women of different age strata with squamous or glandular cervical lesions.

BACKGROUND: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status. METHODS: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. RESULTS: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. CONCLUSIONS: Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.

Incidence, predictive factors, and prognosis for winged scapula in breast cancer patients after axillary dissection.

PURPOSE: Axillary lymph node dissection is part of breast cancer surgery, and winged scapula is a possible sequela. Data regarding its incidence, predictive factors, and patient prognosis remains inconsistent. Ignorance of its diagnosis may lead to undertreatment with physical morbidity. METHODS: Breast cancer patients with axillary lymph node dissection were prospectively recruited. Postoperative examinations by the physiotherapy staff were performed. RESULTS: One hundred eighty-seven patients were recruited during July-October 2012; 51 patients had a positive diagnosis (27.2 %), with 38 patients (86 %) who recovered completely from the winged scapula, while 6 patients (13 %) still had winged scapula at 6 months after surgery. One hundred thirty patients underwent mastectomy and 100 cases had immediate reconstruction. Age, BMI, previous shoulder joint morbidity, and breast surgery were not associated with winged scapula. Neoadjuvant treatment, mastectomy or conservative surgery, immediate reconstruction, tumor size, and nodal involvement also did not show any correlation. Breast reconstruction with prosthesis, even with serratus muscle dissection, does not increase the incidence of winged scapula. CONCLUSION: Winged scapula is not an uncommon incidence after breast cancer surgery. Physiotherapy is related to the complete recovery. The severity or grading of the winged scapula and the recovery time after physiotherapy should be investigated in the future studies.