The caspase family proteases are key proapoptotic proteins while the inhibitor of apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other key proapoptotic proteins. Limited studies of IAPs suggested their deregulation contributed to urothelial neoplasia. However, the expression status and biologic or prognostic significance of the caspase and IAP family proteins in urothelial neoplasms is not clear. In the present study, we first systematically evaluated the expression profile of the major apoptosis regulators, including caspases (CASP3,6,7,8,9,10,and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples by immunohistochemistry. The analysis showed that survivin/ BIRC5 nuclear labeling index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker which correlated significantly with tumor grade, stage, and patient outcome. We further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well as the more classical prognosticators (stage, grade, and Ki67 index) were of prognostic significance. However, multivariate analysis by Cox proportional hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted unfavorable disease-specific survival (relative risk (RR) ¼ 6.6, 95% confidence interval ¼ 1.6-26.7, P ¼ 0.0080) as well as progression-free survival (RR ¼ 4.4, 95% confidence interval ¼ 1.3-14.6, P ¼ 0.0151). We conclude that BIRC5-N is a superior biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary bladder.

Caspases and inhibitor of apoptosis proteins (IAPs) are antagonizing key apoptosis regulators. Limited studies of a few IAPs indicated their roles in astrocytomas. However, the overall expression status and significance of apoptosis regulators in astrocytomas is not clear. We examined the expression profile of the caspases (CASP3, 6, 7, 8, 9, 10, and 14), APAF1, SMAC, BCL2, the IAPs (BIRC5/survivin, CIAP1, CIAP2, XIAP, and LIVIN), and the proliferation markers Ki67 and PHH3 in 78 diffusely infiltrating astrocytomas and 24 normal brain samples by immunohistochemistry. Western blotting for major caspases and IAPs and reverse transcription-polymerase chain reaction analyses for IAPs were performed on a subset of 27 fresh samples. Our data showed BIRC5 nuclear labeling index (BIRC5-N) was the apoptosis marker most significantly different in World Health Organization grade II to IV astrocytomas and most strongly associated with proliferative activity. Expression level of other apoptosis-related proteins was modest or low in astrocytomas and did not correlate significantly with tumor grade or proliferation. Apoptosis regulators and proliferation markers were not detected in astrocytes of normal brain by immunostaining. This expression profile suggested involvement of apoptosis regulators in astrocytoma tumorigenesis, but tumor progression was more closely associated with proliferative advantages of which BIRC5 nuclear expression appeared to be a manifestation.

Rationale: Pulmonary embolisms (PEs) are caused by emboli, which mostly originate from deep venous thrombi that travel to and suddenly block the pulmonary arteries. The emboli are usually thrombi, and right atrial myxoma emboli are rare. Patient concerns: A 55-year-old man presented with shortness of breath and syncope. We proceeded with computed tomography pulmonary angiography (CTPA) and transthoracic echocardiogram (TTE), the results of which suggested that the diagnosis was a right atrial mass. Diagnosis: A definitive diagnosis compatible with a right atrial myxoma (RAM) with tumoral pulmonary emboli after surgical excision was made. Intervention: Right atrial and pulmonary artery embolectomy. Outcomes: The patient followed an uneventful course during the 6 years of follow-up after surgery. According to a review of the literature, RAMs are often not diagnosed in a timely manner or even go completely undiagnosed. TTE, transesophageal echocardiography (TEE), CT, magnetic resonance imaging (MRI), and positron emission tomography/computed tomography may be helpful in the preoperative diagnosis. Surgical removal of the masses from the atrium and pulmonary arteries was relatively uneventful. Lessons: RAMs should be considered unlikely reasons for fatal pulmonary embolisms.

Gastric adenosquamous carcinoma (ASC) is a rare type of gastric cancer. It is a mixed neoplasm, consisting of glandular cells and squamous cells. It is often diagnosed at an advanced stage, thus carrying a poor prognosis. We describe a case of a 73-year-old male, who presented with refractory fever and an intra-abdominal mass on imaging. He underwent a laparoscopic exploration followed by a successful totally laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer. Postoperative pathology revealed primary gastric ASC (T4aN0M0). The patient received adjuvant radiotherapy and chemotherapy with S1 and is alive 20 mo after surgery without recurrence. This is the first case of advanced gastric ASC with fever as the initial presentation treated with totally laparoscopic total gastrectomy reported in the English literature.

Microbial communities significantly inhabit the human body. Evidence shows the interaction between the human microbiome and host cells plays a central role in multiple physiological processes and organ microenvironments. However, the majority of related studies focus on gut microbiota or specific tissues/organs, and the component signature of intratumor microbiota across various cancer types remains unclear. Here, we systematically analyzed the correlation between intratumor microbial signature with survival outcomes, genomic features, and immune profiles across 32 cancer types based on the public databases of Bacteria in Cancer (BIC) and The Cancer Genome Atlas (TCGA). Results showed the relative abundance of microbial taxa in tumors compared to normal tissues was observed as particularly noticeable. Survival analysis found that specific candidate microbial taxa were correlated with prognosis across various cancers. Then, a microbial-based scoring system (MS), which was composed of 64 candidate prognostic microbes, was established. Further analyses showed significant differences in survival status, genomic function, and immune profiles among the distinct MS subgroups. Taken together, this study reveals the diversity and complexity of microbiomes in tumors. Classifying cancer into different subtypes based on intratumor microbial signatures might reasonably reflect genomic characteristics, immune features, and survival status.

Adenosquamous carcinomas of the small intestine are extremely rare, with only three documented jejunal and three ileal cases being reported in the English-language medical literature. Presented herein is a case of primary jejunal adenosquamous carcinoma in an 80-year-old woman. The jejunal carcinoma consisted predominantly of a squamous component throughout the tumor but peritoneal nodules carrying metastases from the adenocarcinoma element were noted, making it the first case of jejunal adenosquamous carcinoma with metastases from the adenocarcinoma component. The finding that metastases could arise from the minor component of a jejunal adenosquamous carcinoma indicates that an accurate diagnosis must be based upon thorough examination of both the primary and the metastases, not just mesenteric nodule biopsy alone. Histological foci of closely intermingled squamous and glandular components with apparent morphological transition were noted, indicating the pathogenetic possibility that the squamous component might arise by transformation from the glandular element. The squamous component was strongly positive with immunostaining for p63 (nuclear staining) and for cytokeratin 10/13 (cytoplasmic staining), while the adenocarcinoma element was negative. The immunohistochemical results suggest that p63 and cytokeratin 10/13 might be useful in identifying squamous differentiation in jejunal carcinoma.

As a small number of asymptomatic MMD patients have clinical symptoms, we must be aware of the possibility of MMD. The clinical symptoms of transient ischemic attack, ischemic stroke, or/and intracranial bleeding maybe the manifestation of this disease. Early recognition, accurate diagnosis and prompt treatment are vital to the survival of the patients with asymptomatic MMD.

Background: The high heterogeneity of triple negative breast cancer (TNBC) is the main clinical challenge for individualized therapy. Considering that fatty acid metabolism (FAM) plays an indispensable role in tumorigenesis and development of TNBC, we proposed a novel FAM-based classification to characterize the tumor microenvironment immune profiles and heterogeneous for TNBC. Methods: Weighted gene correlation network analysis (WGCNA) was performed to identify FAM-related genes from 221 TNBC samples in Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. Then, non-negative matrix factorization (NMF) clustering analysis was applied to determine FAM clusters based on the prognostic FAM-related genes, which chosen from the univariate/multivariate Cox regression model and the least absolute shrinkage and selection operator (LASSO) regression algorithm. Then, a FAM scoring scheme was constructed to further quantify FAM features of individual TNBC patient based on the prognostic differentially expressed genes (DEGs) between different FAM clusters. Systematically analyses were performed to evaluate the correlation between the FAM scoring system (FS) with survival outcomes, genomic characteristics, tumor microenvironment (TME) features and immunotherapeutic response for TNBC, which were further validated in the Cancer Genome Atlas (TCGA) and GSE58812 datasets. Moreover, the expression level and clinical significancy of the selected FS gene signatures were further validated in our cohort. Results: 1860 FAM-genes were screened out using WGCNA. Three distinct FAM clusters were determined by NMF clustering analysis, which allowed to distinguish different groups of patients with distinct clinical outcomes and tumor microenvironment (TME) features. Then, prognostic gene signatures based on the DEGs between different FAM clusters were identified using univariate Cox regression analysis and Lasso regression algorithm. A FAM scoring scheme was constructed, which could divide TNBC patients into high and low-FS subgroups. Low FS subgroup, characterized by better prognosis and abundance with effective immune infiltration. While patients with higher FS were featured with poorer survival and lack of effective immune infiltration. In addition, two independent immunotherapy cohorts (Imvigor210 and GSE78220) confirmed that patients with lower FS demonstrated significant therapeutic advantages from anti-PD-1/PD-L1 immunotherapy and durable clinical benefits. Further analyses in our cohort found that the differential expression of CXCL13, FBP1 and PLCL2 were significantly associated with clinical outcomes of TNBC samples. Conclusions: This study revealed FAM plays an indispensable role in formation of TNBC heterogeneity and TME diversity. The novel FAM-based classification could provide a promising prognostic predictor and guide more effective immunotherapy strategies for TNBC.