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List of 40 genes in next-generation sequencing (NGS) panel

PCR-based assays to detect human circulating DNA in mice demonstrate that human PTEGR2 assays are specific (A) and sensitive (B). Human-derived DNA could be detected in plasma of PDX (C).

Pathologists diagnose prostate cancer by core needle biopsy. For low-grade and low-volume cases, the pathologists look for the few malignant glands out of hundreds within a core. They may miss the few malignant glands, resulting in repeat biopsies or missed therapeutic opportunities. This study developed a multi-resolution deep learning pipeline detecting malignant glands in core needle biopsies to help pathologists effectively and accurately diagnose prostate cancer in low-grade and low-volume cases. The pipeline consisted of two stages: the gland segmentation model detected the glands within the sections and the multi-resolution model classified each detected gland into benign vs. malignant. Analyzing a gland at multiple resolutions provided the classification model to exploit both morphology information (of nuclei and glands) and neighborhood information (for architectural patterns), important in prostate gland classification. We developed and tested our pipeline on the slides of a local cohort of 99 patients in Singapore. The images were made publicly available, becoming the first digital histopathology dataset of prostatic carcinoma patients of Asian ancestry. Our pipeline successfully classified the core needle biopsy parts (81 parts: 50 benign and 31 malignant) into benign vs. malignant. It achieved an AUROC value of 0.997 (95% CI: 0.987 - 1.000). Moreover, it produced heatmaps highlighting the malignancy of each gland in core needle biopsies. Hence, our pipeline can effectively assist pathologists in core needle biopsy analysis.

There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer. Metformin (150 mg/kg) as a single agent inhibits the growth of both PDX tumors by at least 50% (P < 0.05) when administered orally for 24 days. In one of the PDX models, metformin given concurrently with 5-FU (25 mg/kg) leads to an 85% (P = 0.054) growth inhibition. Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. In addition, we also performed genetic characterizations of serial PDX samples with corresponding parental tissues from patients using next-generation sequencing (NGS). Our pilot NGS study demonstrates that PDX represents a useful platform for analysis in cancer research because it demonstrates high fidelity with parental tumor. Furthermore, NGS analysis of PDX may be useful to determine genetic identifiers of drug response. This is the first preclinical study using PDX and PDX-derived organoids to investigate the efficacy of metformin in colorectal cancer. Mol Cancer Ther; 16(9); 2035–44. ©2017 AACR.

Meningiomas are usually low-grade, solitary lesions that rarely metastasize. In this group of central nervous system tumours, the higher grade subtypes are notorious for resistance to conventional chemo-radiation therapies. Recent studies have shown efficacy in the use of bevacizumab in patients with recurrent and, or progressive anaplastic meningioma. The authors report a case of a young patient with recurrent anaplastic meningioma who despite being treated with bevacizumab, progressed with disease dissemination to multiple extracranial sites. Although the majority of meningiomas are amendable to treatment, the higher grade subtypes remain therapeutically challenging. The unexpected resistance to anti-angiogenic therapy in this patient adds another layer of complexity to an elusive subset of a supposedly benign disease. This patient report reflects the need for in-depth studies, molecular characterization and overall, better disease understanding in order to improve prognosis for affected patients.

We report a case of a woman who was admitted with a suspicion of metastatic malignancy of unknown primary origin. A few months prior to her admission, she presented to a rheumatologist with acute anterior uveitis, psoriasiform rashes and polyarthritis. A diagnosis of psoriatic arthropathy was made and she was treated accordingly. Soon after she presented with persistent back and right upper quadrant abdominal pain for which she had a CT scan done with evidence of hilar lymphadenopathy, liver hypodensities and lytic-sclerotic bone lesions. She was referred to our hospital for further investigations and management. After re-exploring her clinical presentation and further investigations (including a liver biopsy), a diagnosis of multisystemic sarcoidosis with ocular, reticuloendothelial, hepatic and skeletal involvement was made. The patient was started on systemic glucocorticoids and second line immunosuppressants and demonstrated significant clinical improvement with resolution of her liver granulomata on imaging and improvement in her back pain. The case illustrates the importance of a thorough clinical assessment, review of investigations and an open mind in the evaluation of a patient.

Cerebral amyloid angiopathy–related inflammation (CAA-I) was first described in 2004 with 7 cases of perivascular inflammation in patients with CAA.1 So far

Primary malignant mixed Mullerian tumour (MMMT) of the vagina is a rare entity. We report a case of a 62-year-old woman who presented with a fixed and hard anterior vaginal wall mass with contact bleeding. She proceeded to have an anterior infralevator pelvic exenteration with urethrectomy and anterior vaginectomy, creation of an ileal conduit and bilateral lymph node dissection. Histopathological examination and immunohistochemistry confirmed the diagnosis of primary MMMT of the vagina. The patient was stage IVA at diagnosis. Despite chemotherapy and radiotherapy, she had progressive disease and eventually passed away at the age of 65 years.