Case report: Secretory breast cancer in an 11-year-old girl

AbstractA lack of consensus about the optimal treatment modalities for breast cancer in children is because of its absolutely rare prevalence. In this article, the medical history and treatment of a secretory breast carcinoma in an 11-year-old girl is reported. Modified radical mastectomy (MRM) was performed on April 6, 2013. Systemic chemotherapy was performed after surgery because metastatic lymph nodes were found in the dissected axillary tissue. Long term follow-up had to be done

A randomized clinical trial on the anti-tumoral effects of low molecular weight heparin in the treatment of esophageal cancer

The current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low‐molecular‐weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single‐blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy‐only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8‐Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4–6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease‐free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups ( p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment‐related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively ( p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow‐up and a larger sample size are required.delivered in 1.8-Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) daily as well as chemoradiation. Four to six weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months,estimated one year disease free survival (1y DFS) in the intervention group was 78.9% and in the control groups was 70% (p=0.5). Toxicity from the experimental treatment was minimal and there were no treatment-related deaths. A Pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively (p=0.9). There was a non-significant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1y DFS of both groups were high as expected. A longer follow-up and larger sample size is required

A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with 1 esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661 and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced OS of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5±8.9 months vs. CG+GG: 47.7±5.9 months; p value= 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of ESCC patients. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC. Key word: Esophageal squamous cell carcinoma, risk marker, CDKN2A/B, polymorphis

The clinical application of Circulating tumor cells and DNAs as prognostic and predictive biomarkers in gastrointestinal cancer

Gastrointestinal (GI) cancer is one of the most common cancers globally. Genetic and epigenetic mechanisms are involved in its pathogenesis. The conventional methods for diagnosis and screening for GI cancers are often invasive and have other limitations. In the era of personalized medicine, a novel non-invasive approach called liquid biopsy has been introduced for the detection and management of GI cancers, which focuses on the analysis of circulating tumor cells (CTCs) and circulating cell-free tumor DNA (ctDNA). Several studies have shown that this new approach allows for an improved understanding of GI tumor biology and will lead to an improvement in clinical management. The aim of the current review is to explore the clinical applications of CTCs and ctDNA in patients with GI cancer. Key words: Gastrointestinal cancer; Liquid biopsy; CTCs; ctDNA; biomarkers; tumor biolog

Predictive Value of Endoscopic Observations and Biopsy After Neoadjuvant Chemoradiotherapy in Assessing the Pathologic Complete Response of Patients With Esophageal Squamous Cell Carcinoma

INTRODUCTION: No standard method has been defined to evaluate the therapeutic response of esophageal cancer to neoadjuvant chemoradiotherapy (CRT). This study aimed to determine the predictive value of endoscopic evaluation and biopsy after CRT in predicting the complete pathological response to neoadjuvant CRT in patients with esophageal squamous cell carcinoma (SCC). MATERIALS AND METHOD: This prospective, descriptive study was conducted on patients with stage II and III esophageal SCC who could undergo esophagectomy. Patients underwent neoadjuvant CRT. Four to six weeks after the end of treatment, re-endoscopy was performed and a biopsy was taken in the presence of a tumor lesion. In the absence of a tumor lesion, the marked site of the esophagus was removed as a blind biopsy. Gastrologist observations during endoscopy and the result of the pathological examination of an endoscopic biopsy were recorded. The patient underwent esophagectomy. The pathology obtained from endoscopic biopsy was compared with the pathology response obtained from esophagectomy. RESULTS: Sixty-nine patients were included in the study, of which 32 underwent esophagectomy. In an endoscopic examination after CRT, 28 patients had macroscopic tumor remnants and 4 patients did not. Pathological examination of the samples obtained from endoscopy showed no tumor remnants in 10 patients (31.3%), and in 22 patients (68.7%), living tumor remnants were seen in the biopsy specimen. Pathologic evaluation of the samples obtained by surgical resection showed that in 13 patients, there were no viable carcinomas in the esophagus or lymph nodes removed, and the rate of pathologic complete response was 40.6. Sensitivity, specificity, positive predictive, and negative predictive values of endoscopic observations were 94.7, 23, 64.2, and 75%, respectively. Preoperative biopsy sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 68.4, 30.7, 59, and 40%, respectively. CONCLUSION: Considering the negative and positive predictive values of endoscopic observations and biopsy after neoadjuvant CRT, it seems that these two methods alone are not suitable for assessing the pathologic complete response after neoadjuvant treatment

Clinicopathologic Features and Survival of Breast Cancer Subtypes in Northeast Iran

Background: Breast cancer can be categorized into different histopathological subtypes based on gene expression profiles. This study aims to evaluate the clinicopathological features and overall survival of various subtypes of breast cancer to assist diagnosis and guide treatment. Methods: The clinicopathologic features of 1095 patients with breast cancer diagnosed over a 10–year period between 2001 and 2011 were analyzed. The Kaplan–Meier method was used to analyze disease-free survival and overall survival. Calculation of the hazard ratio was conducted by multivariate Cox regression. Results: According to the clinicopathologic characteristics of 1095 cases, there were 42% luminal A subtype, 19.2% luminal B, 23% triple negative, and 15% HER2+. The lowest (46.88±12.59 years) and highest (50.54±12.32 years) mean ages were in the triple negative and HER2+ groups, respectively. There was a significant correlation between histology subtype and age, BMI, lymph node, type of surgery, and stage of disease. There was significantly shorter overall survival and disease free survival in HER2+ breast cancer patients (P<0.001). Multivariate analysis showed that age had the highest hazard ratio of 2.481 (95% Confidence Interval: 1.375-4.477). Conclusion: The results of this study showed the importance of clinicopathological studies of molecular types which help early diagnosis and identification of the best strategy to treat breast cancer

Inhibition of the Wnt/b-catenin pathway using PNU-74654 reduces tumor growth in in vitro and in vivo models of colorectal cancer

Background Colorectal-cancer (CRC) is amongst the most lethal-cancers, mainly due to its metastatic spread and drug chemoresistance. Hence there is a need for new approaches to either increase the efficacy of current therapy or introduce new therapies that have greater efficacy. There is increasing evidence that dysregulation of WNT-signaling-pathway plays an essential role in the development and prognosis of CRC. Here we have investigated the therapeutic potential of targeting the WNT/b-catenin pathway using a novel Wnt/b-catenin inhibitor, PNU-74654, in combination with 5-FU in CRC. Methods The anti-proliferative-effect of PNU-74654 was evaluated in two-/three-dimensional cell models. The activity of agents on cell growth, migration, invasion, cell cycle and apoptosis was evaluated by MTT, wound healing assay, invasion, FACS, and annexin V staining, respectively. The oxidant/antioxidant levels were also assessed by determining the level of MDA, SOD, as well as using the DCFH-DA assay. We used a xenograft model of CRC to investigate PNU-74654 activity alone and in combination with 5-FU follow by histological staining and biochemical and gene expression analyses by RT-PCR and western blot. Results PNU-74654 inhibited cell-growth and synergistically affected the anti-tumor properties of 5-FU via modulation of Cyclin D1 and survivin. This agent inhibited the migration/invasion of colorectal cancer cells via perturbation of E-cadherin. Furthermore, PNU-74654 inhibited the tumor growth, which was more pronounced using the PNU-74654 plus 5-FU combination via induction of reactive oxygen species, down-regulation of SOD and modulation of MCP-1, P53, TNF-α. Conclusions Our finding demonstrated that PNU-74654 can target Wnt-pathway, interfere with cell-proliferation, induced-cell death, reduced-migration and interact with 5-FU, supporting further investigations on this therapeutic-approach for colorectal cancer

A cohort study on the immunogenicity and safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with breast cancer; does trastuzumab interfere With the outcome?

Aim To determine the efficacy and safety of inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with breast cancer. Methods In this multi- institutional cohort study, a total of 160 breast cancer patients (mean age of 50.01 ± 11.5 years old) were assessed for the SARS-CoV-2 Anti-Spike IgG and SARS-CoV2 Anti RBD IgG by ELISA after two doses of 0.5 mL inactivated, COVID-19 vaccine (BBIBP-CorV). All patients were followed up for three months for clinical COVID-19 infection based on either PCR results or imaging findings. Common Terminology Criteria for Adverse Events were used to assess the side effects. Results The presence of SARS-CoV-2 anti-spike IgG, SARS-CoV2 anti-RBD IgG, or either of these antibodies was 85.7%, 87.4%, and 93.3%. The prevalence of COVID-19 infection after vaccination was 0.7%, 0% and 0% for the first, second and third months of the follow-up period. The most common local and systemic side-effects were injection site pain and fever which were presented in 22.3% and 24.3% of patients, respectively. Discussion The inactivated SARS-CoV-2 vaccine (BBIBP-CorV) is a tolerable and effective method to prevent COVID-19

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2013-2018, Adult and Pediatric Units, Device-associated Module

•Data from 428,847 patients, 2,815,402 bed-days.•We collected 1,468,216 line days, 1,053,330 ventilator days, 1,740,776 urinary catheter days.•We found 7,785 CLAB, 12,085 VAE, and 5,509 CAUTI.•HAI rates were 5.91% and 9.01 HAIs/1,000 bed-days.•CLAB rate was 5.3/1000 CL-days; VAE rate was 11.4/1000 MV-days, CAUTI rate was 3.1/1000 UC-days. We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them