Knockdown of Hoxa11 in vivo in the uterosacral ligament and uterus of mice results in altered collagen and matrix metalloproteinase activity.

Homeobox (HOX) genes are evolutionarily conserved genes encoding transcription factors that regulate mammalian embryonic growth and development of the urogenital tract. In both humans and mice, HOXA11 persists in the adult reproductive tract and is thought to play an important role in maintaining tissue developmental plasticity by regulating the expression of genes involved in extracellular matrix metabolism in the reproductive organs. Previously, we have shown that HOXA11 is necessary for development of the uterosacral ligaments in mice and is deficient in women with pelvic organ prolapse. Therefore, we hypothesized that Hoxa11 regulates the synthesis and/or metabolism of collagens in the uterosacral ligaments and uterus, and tested this by establishing an in utero and peritoneal Hoxa11 gene knockdown system in C57/BL6 mice using vectors bearing Hoxa11 short hairpin RNA. Specific knockdown of Hoxa11 transcripts and protein levels were confirmed versus control vectors. Protein and mRNA expression of collagen types I and III exhibited significant decreases following Hoxa11 knockdown according to Western blot analysis and real-time PCR. Tissue inhibitor of matrix metalloproteinase 1 (MMP1) expression also exhibited a significant decrease. Gelatinase zymography confirmed increases in pro-MMP2 and MMP9, as well as activated MMP2, following Hoxa11 knockdown. These results reveal that Hoxa11 knockdown in the uterosacral ligaments and uterus increases extracellular matrix degradation. More importantly, it suggests a mechanism in the weakening of the pelvic floor support in women, because decreased HOXA11 gene expression has been reported to be associated with decreased collagen and increased MMP2 expression in the uterosacral ligaments of women with pelvic organ prolapse.

Open versus minimally invasive surgery for suspected adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Although laparoscopy has been widely adopted for management of benign adrenal tumors, minimally invasive surgery for ACC remains controversial. Retrospective analyses, frequently with fewer than one hundred participants, comprise the majority of the literature. High-quality data regarding the optimal surgical approach for ACC are lacking due to the rarity of the disease and the fact that determination of tumor type (e.g., adenoma or carcinoma) is determined after adrenalectomy, since adrenal tumors are generally not biopsied. While the benefits of minimally invasive surgery including lower intra-operative blood loss and decreased hospital length-of-stay have been consistently demonstrated, clinical equipoise for long-term survival and recurrence outcomes between open and minimally invasive adrenalectomy (MIA) remains. This review examines retrospective studies that directly compare patients with ACC who underwent either open or laparoscopic adrenalectomy, and considers these findings in the context of current guideline recommendations for surgical management of ACC.

Case report: Adenosquamous carcinoma of the prostate with greater than 20 month response to multimodal therapy.

Adenosquamous carcinoma is an extremely rare and lethal subtype of prostate cancer affecting an estimated 0.03 per million men annually. It has been associated with prior hormone therapy for prostate adenocarcinoma. We present a case of de novo adenosquamous carcinoma of the prostate treated with a multimodal approach including surgery, androgen-deprivation therapy, chemotherapy, and radiation.

Hematospermia and Cloacogenic Transitional Cell Carcinoma: A Twist on Significance and Meaning.

A 52-year-old gentleman presented with recurrent hematospermia. Further history revealed recent onset of constipation and difficulty voiding. Rectal examination revealed a firm, polypoid mass and colonoscopy showed suspicious, ulcerated lesions of the rectal mucosa with narrowing of the rectal vault. Pathology demonstrated transitional cell carcinoma of the rectum. While transitional cell carcinoma is a common genitourinary cancer, its presence in the anus and rectum is exceedingly rare. Furthermore, hematospermia is generally not associated with malignancy. This case is a remarkable example of two pathologic processes presenting in rare form and underscores the value of a thorough investigation of hematospermia when associated with other clinical symptoms.