Prognostic Value of Tumor Budding for Early Breast Cancer.

BACKGROUND: Tumor budding (TB) is a dynamic process associated with the epithelial-mesenchymal transition and a well-established prognostic biomarker for colorectal cancer. As part of the tumor microenvironment, tumor buds demonstrate increased cell motility and invasiveness. Current evidence demonstrates that high levels of TB correlate with disease progression and worst outcomes across different solid tumors. Our work aims to demonstrate the clinical applicability of TB analysis and its utility as a prognostic factor for patients with early breast cancer (EBC). METHODS: Retrospective, single-center, observational study, enrolling patients with EBC diagnosed in a Portuguese hospital between 2014 and 2015. TB classification was performed according to the International Tumor Budding Conference 2016 guidelines. RESULTS: A statistically significant relation was found between higher TB score and aggressive clinicopathological features (angiolymphatic/perineural invasion-p < 0.001; tumor size-p = 0.012; nuclear grading-p < 0.001; and Ki-67 index-p = 0.011), higher number of relapses (p < 0.001), and short disease-free survival (DFS) (p < 0.001). CONCLUSION: We demonstrate that high TB correlates with shorter DFS and aggressive clinicopathological features used in daily practice to decide on the benefit of chemotherapy for EBC. TB represents a needed prognostic biomarker for EBC, comprising a new factor to be considered in the adjuvant decision-making process by identifying patients at a high risk of relapse and with higher benefit on treatment intensification. Clinical trials incorporating TB are needed to validate its prognostic impact.

Sarcomatoid Cholangiocarcinoma of the Common Bile Duct: An Unusual Entity.

Sarcomatous carcinoma of the bile duct is tremendously uncommon and aggressive. Herein, we report a case of a male who presented with jaundice. The thoraco-abdominopelvic tomography scan revealed a lesion within the common bile duct highly suspicious of malignancy. After laparoscopic pancreaticoduodenectomy, histological examination revealed a sarcomatous carcinoma. Two years after the initial diagnosis, the patient remains without signs of recurrence. Additional research about this rare condition is needed to improve care and prognosis.

Molecular insights of Hippo signaling in the chick developing lung.

Hippo signaling pathway and its effector YAP have been recognized as an essential growth regulator during embryonic development. Hippo has been studied in different contexts; nevertheless, its role during chick lung branching morphogenesis remains unknown. Therefore, this work aims to determine Hippo role during early pulmonary organogenesis in the avian animal model. The current study describes the spatial distribution of Hippo signaling members in the embryonic chick lung by in situ hybridization. Overall, their expression is comparable to their mammalian counterparts. Moreover, the expression levels of phosphorylated-YAP (pYAP) and total YAP revealed that Hippo signaling is active in the embryonic chick lung. Furthermore, the presence of pYAP in the cytoplasm demonstrated that the Hippo machinery distribution is maintained in this tissue. In vitro studies were performed to assess the role of the Hippo signaling pathway in lung branching. Lung explants treated with a YAP/TEAD complex inhibitor (verteporfin) displayed a significant reduction in lung size and branching and decreased expression of ctgf (Hippo target gene) compared to the control. This approach also revealed that Hippo seems to modulate the expression of key molecular players involved in lung branching morphogenesis (sox2, sox9, axin2, and gli1). Conversely, when treated with dobutamine, an upstream regulator that promotes YAP phosphorylation, explant morphology was not severely affected. Overall, our data indicate that Hippo machinery is present and active in the early stages of avian pulmonary branching and that YAP is likely involved in the regulation of lung growth.

Clinical relevance of receptor conversion in metastatic breast cancer: Case report.

INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression. PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012. DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative. INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated. OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events. CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.

Chronic Copper Sulfate Poisoning.

Copper, as a salt, is toxic and has the potential to harm multiple organs. Copper intoxication causes intravascular haemolysis followed by liver and kidney failure that can be fatal. We present a case of chronic copper sulfate poisoning in a 66-year-old man with dysphagia to solids and liquids, anaemia, acute kidney injury, liver cytolysis and hypocalcaemia. The patient improved with supportive care, but chronic kidney disease was established. Anamnesis was crucial for the diagnosis, given the non-specific signs and symptoms. The history of chronic exposure to pest treatment with a blue dust cloud made us suspect copper sulfate poisoning. LEARNING POINTS: Copper sulfate poisoning is a relatively uncommon illness nowadays but can still be seen in clinical practice and should be kept in mind.It has non-specific signs and symptoms such as dysgeusia, abdominal pain, vomiting, muscle cramps or spasms, diarrhoea, ink-like urine, jaundice, anaemia and seizures.The diagnosis is based on clinical presentation and laboratory examinations upon a history of exposure to copper sulfate-containing products.

Fulminant Emphysematous Hepatitis - A Rare Cause of Septic Shock.

Emphysematous hepatitis is a rare entity characterized by the replacement of hepatic parenchyma by gas, leading to acute liver failure. Often it occurs in patients with diabetes mellitus, liver disease or a recent history of abdominal surgery. We present a case of emphysematous hepatitis in a 74-year-old man with no recognizable risk factors. Despite the early broad-spectrum antimicrobial therapy and supportive care, the condition progressed to a fatal outcome, as seen in other case reports. Early recognition of this condition and rapid and aggressive management may improve patient outcomes. LEARNING POINTS: Emphysematous hepatitis is a rare condition characterized by replacement of hepatic parenchyma by gas.The diagnosis of emphysematous hepatitis requires imaging, preferably a computed tomography scan.Emphysematous hepatitis warrants awareness among clinicians for early diagnosis and rapid and aggressive management.