Ex vivo metabolism kinetics of primary to secondary bile acids via a physiologically relevant human faecal microbiota model.

Bile acids (BA) are synthesized in the human liver and undergo metabolism by host gut bacteria. In diseased states, gut microbial dysbiosis may lead to high primary unconjugated BA concentrations and significant perturbations to secondary BA. Hence, it is important to understand the microbial-mediated formation kinetics of secondary bile acids using physiologically relevant ex vivo human faecal microbiota models. Here, we optimized an ex vivo human faecal microbiota model to recapitulate the metabolic kinetics of primary unconjugated BA and applied it to investigate the formation kinetics of novel secondary BA metabolites and their sequential pathways. We demonstrated (1) first-order depletion of primary BA, cholic acid (CA) and chenodeoxycholic acid (CDCA), under non-saturable conditions and (2) saturable Michaelis-Menten kinetics for secondary BA metabolite formation with increasing substrate concentration. Notably, relatively lower Michaelis constants (Km) were associated with the formation of deoxycholic acid (DCA, 14.3 µM) and lithocholic acid (LCA, 140 µM) versus 3-oxo CA (>1000 µM), 7-keto DCA (443 µM) and 7-keto LCA (>1000 µM), thereby recapitulating clinically observed saturation of 7α-dehydroxylation relative to oxidation of primary BA. Congruently, metagenomics revealed higher relative abundance of functional genes related to the oxidation pathway as compared to the 7α-dehydroxylation pathway. In addition, we demonstrated gut microbial-mediated hyocholic acid (HCA) and hyodeoxycholic acid (HDCA) formation from CDCA. In conclusion, we optimized a physiologically relevant ex vivo human faecal microbiota model to investigate gut microbial-mediated metabolism of primary BA and present a novel gut microbial-catalysed two-step pathway from CDCA to HCA and, subsequently, HDCA.

A Literature Review and Case Report of Metastatic Pure Choriocarcinoma.

In 2012, testicular cancer was estimated to account for 940 disability adjusted life years in Australia; of these, 450 were years lost due to premature death and 500 were years of healthy life lost due to disease, disability, or injury (Australian Institute of Health and Welfare and Australasian Association of Cancer Registries, 2012). Testicular choriocarcinoma is one of the rarest variants of testicular germ cell tumours, accounting for less than 1% of testicular germ cell tumours and only about 0.19% of all testicular tumours. Management involves radical orchidectomy and chemotherapy. Even then, prognosis is poor. This case report describes a 20-year-old male with pure testicular choriocarcinoma with pulmonary metastases which showed sustained and complete response to adjuvant chemotherapy consisting of bleomycin, etoposide, and cisplatin.

A rare case of large cell neuroendocrine carcinoma.

We present a very rare case of de novo large cell neuroendocrine carcinoma (LCNEC) of the prostate in an 84-year-old man on a background of high grade, superficially invasive transitional cell carcinoma of the bladder. Pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate are thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing neuroendocrine differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease and a worse prognosis.

One lump or two? Concomitant Leydig cell tumour and paratesticular leiomyoma in an adult man.

We present the first reported case of a concomitant Leydig cell tumour (LCT) and paratesticular leiomyoma in an adult man with a history of bilateral cryptorchidism. An 80-year-old man presented with a 2-month history of a left testicular lump associated with mild discomfort and a gradual increase in size on a background of bilateral cryptorchidism requiring multiple orchidopexy procedures as a child. Ultrasound confirmed a lesion suspicious for malignancy and he proceeded to a left radical orchidectomy. Histopathological assessment of the left testis revealed a concomitant testicular LCT with rare malignant features and paratesticular leiomyoma.