Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Controversial Indications for Sentinel Lymph Node Biopsy in Breast Cancer Patients

Sentinel lymph node biopsy (SLNB) emerged in the 1990s as a new technique in the surgical management of the axilla for patients with early breast cancer, resulting in lower complication rates and better quality of life than axillary lymph node dissection (ALND). Today SLNB is firmly established in the armamentarium of clinicians treating breast cancer, but several questions remain. The goal of this paper is to review recent work addressing 4 questions that have been the subject of debate in the use of SLNB in the past few years: (a) What is the implication of finding micrometastases in the sentinel nodes? (b) Is ALND necessary in all patients who have a positive SLNB? (c) How accurate is SLNB after neoadjuvant therapy? (d) Can SLNB be used to stage the axilla in locally recurrent breast cancer following breast surgery with or without prior axillary surgery

Controversial Indications for Sentinel Lymph Node Biopsy in Breast Cancer Patients

Sentinel lymph node biopsy (SLNB) emerged in the 1990s as a new technique in the surgical management of the axilla for patients with early breast cancer, resulting in lower complication rates and better quality of life than axillary lymph node dissection (ALND). Today SLNB is firmly established in the armamentarium of clinicians treating breast cancer, but several questions remain. The goal of this paper is to review recent work addressing 4 questions that have been the subject of debate in the use of SLNB in the past few years: (a) What is the implication of finding micrometastases in the sentinel nodes? (b) Is ALND necessary in all patients who have a positive SLNB? (c) How accurate is SLNB after neoadjuvant therapy? (d) Can SLNB be used to stage the axilla in locally recurrent breast cancer following breast surgery with or without prior axillary surgery

Treatment Strategies for Residual Disease following Neoadjuvant Chemotherapy in Patients with Early-Stage Breast Cancer

Breast cancer continues to be the most diagnosed cancer among women worldwide. Neoadjuvant chemotherapy is the standard of care for breast cancer patients with locally advanced disease and patients with poor pathological features, such as triple-negative (TN) or human epidermal growth factor receptor-2 (HER2)-positive subtypes. Neoadjuvant therapy offers several advantages, including better surgical outcomes, early systemic treatment for micro-metastases, and accurate tumor biology and chemosensitivity assessment. Multiple studies have shown that achieving pathological complete response (pCR) following neoadjuvant chemotherapy is associated with better prognosis and better treatment outcomes; almost half of such patients may fail to achieve pCR. Tumor proliferative index, hormone receptor (HR) status, and HER2 expression are the major predictors of pCR. Strategies to improve pCR have been dependent on augmenting neoadjuvant chemotherapy with the addition of taxanes and dual anti-HER2 targeted therapy in patients with HER2-positive tumor, and more recently, immunotherapy for patients with TN disease. The clinical management of patients with residual disease following neoadjuvant chemotherapy varies and depends mostly on the level of HR expression and HER2 status. Recent data have suggested that switching trastuzumab to trastuzumab-emtansine (T-DM1) in patients with HER2-positive disease and the addition of capecitabine for patients with HER2-negative and HR-negative subtype is associated with a better outcome; both strategies are incorporated into current clinical practice guidelines. This paper reviews available and ongoing studies addressing strategies to better manage patients who continue to have residual disease following neoadjuvant chemotherapy

Primary small cell carcinoma of the breast: a case report

Abstract Background Neuroendocrine breast cancer is a rare entity that was defined in 2003 by the World Health Organization as a separate breast cancer subtype. The diagnosis of neuroendocrine breast cancer requires the presence of neuroendocrine features in at least 50% of malignant cells, the exclusion of non-mammary primary tumors, as well as the presence of an in situ component in breast histology. The treatment and prognosis of neuroendocrine breast cancer are still not well established. Small cell carcinoma of the breast is a subtype of neuroendocrine cancer, resembling small cell carcinoma of the lung. It has a very poor prognosis and warrants treatment with platinum-based chemotherapy. Case presentation We herein report the case of a 47-year-old white woman with a left breast mass that was found to be an early-stage, high-grade small cell carcinoma of the breast. Positron emission tomography-computed tomography imaging excluded any other primary disease. Our patient underwent a left total mastectomy with sentinel lymph node biopsy and received cisplatin-based adjuvant chemotherapy. Our patient remains free of disease to date. Conclusions This case report sheds light on a rarely described disease and provides a comprehensive approach to diagnosis and management. Neuroendocrine carcinoma of the breast is a well-defined histologic subtype of breast cancer. Small cell carcinoma of the breast is a rare subtype of neuroendocrine breast cancer. Due to the rarity of this entity, prognosis has still not been well established, and treatment has not been standardized, cisplatin-based treatment has been used in this case similar to small cell carcinoma of the lung

Metabolic Syndrome: Updates on Pathophysiology and Management in 2021

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome

PTEN R130Q Papillary Tumor of the Pineal Region (PTPR) with Chromosome 10 Loss Successfully Treated with Everolimus: A Case Report

Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and PTEN gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR