UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.

The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC.

Case Report of Hemosuccus Pancreaticus as a Result of Endovascular Coil Erosion.

BACKGROUND: Hemosuccus pancreaticus (HP) remains one of the rarest causes of gastrointestinal (GI) bleeding. Due to its rarity, diagnostic and treatment strategies for this condition remain poorly defined. Endoscopy is commonly inconclusive as the hemorrhaging from the papilla of Vater is intermittent. CASE SUMMARY: We describe a 36-year-old female with a remote history of alcoholic pancreatitis who presented with a two year history of recurrent gastrointestinal hemorrhages requiring frequent admission to the intensive care unit and frequent blood transfusion. She had undergone eight endoscopies in two years. Despite undergoing four endovascular procedures including coiling of the left gastric artery and microvascular plugging of the gastroduodenal and supraduodenal artery, her symptoms failed to resolve. She subsequently underwent surgical pancreatectomy which resulted in complete resolution of her bleeding. CONCLUSION: GI bleeds resulting from hemosuccus pancreaticus can often go undiagnosed following multiple negative workups. Diagnosis of HP is often through endoscopic imaging along with radiological evidence. Endovascular procedures are useful treatments in certain populations. Pancreatectomies are recommended after all other therapeutics fail to resolve the bleeding.

Pararectal hernia: literature review and surgical repair techniques in the era of robotic surgery.

A pelvic hernia is the protrusion of intraperitoneal or extraperitoneal contents into the perineum through a defect in the pelvic floor. Pelvic hernias are rare with no gold standard method for repair. After abdominoperineal resection, a commonly cited incidence of perineal hernia is 1%. Here, we describe a robotic repair of a pararectal hernia in a post-menopausal women presenting with rectal herniation through a pelvic floor defect causing issues with fecal urgency and incontinence.

Overview and Management of Small Bowel Obstruction versus Ileus: A Primer for All Physicians.

The conditions of small bowel obstruction and ileus are ones with a great deal of overlap with respect to presentation and differential diagnosis but vary substantially with respect to management. These disorders are frequently encountered by members of the healthcare team across almost every specialty in one way or another. Understanding safe and expeditious methods to identify and distinguish these conditions is important for all providers to understand. This article aims to compare both disorders, briefly discuss the pathophysiology and presentation, give a differential diagnosis for these disorders, and pursue a course of diagnosis and therapy in an appropriate, safe, and cost-effective manner.

Transanal stricturoplasty: a minimally-invasive approach to a challenging problem.

Despite the advances in the surgical techniques and technology in colorectal surgery, the development of rectal anastomotic stricture is a common problem. In some case series, the incidence is estimated to be as high as 30%. Some of the known risk factors for developing a stricture include anastomotic leak and ischemia. Treatment options range from frequent dilations using digital rectal examinations and dilators if the stricture is low or endoscopic balloon dilations for higher strictures. Unfortunately, multiple sessions are typically required to achieve adequate results. We present a case report of a benign anastomotic stricture and describe a novel approach, transanal stricturoplasty, for this challenging problem.

Annular Pancreas in Adults: Case Report and Literature Review.

Annular pancreas is an uncommon congenital cause of gastric outlet obstruction. The incidence is usually referenced at between five and 15 per 100,000 based on autopsy series. When present, this rare condition surfaces with symptoms in the pediatric population during the first few months of life. An adult presenting with symptoms of gastric outlet obstruction due to annular pancreas is an unusual incident. This case describes gastric outlet obstruction due to a partial annular pancreatic band in an otherwise healthy 32-year-old male. Given the scarcity of this pathological process in adults; no specific guidelines exist about the management of this condition. Continued reporting of this pathology is essential for development of such guidelines. Literature review, embryology and treatment options will be discussed.

Ascending Colon Schwannoma an Unusual Cause of Acute Lower Gastrointestinal Bleeding.

This is a case report of a 61-year-old female who presented with acute lower gastrointestinal bleeding resulting from a schwannoma involving the ascending colon. The patient was successfully treated with laparoscopic hemicolectomy. Schwannoma involving the large bowel is a rare entity; only around 90 cases of colonic schwannomas are reported in world literature. Although the vast majority of these tumors demonstrate a slow growing and benign profile, recurrence and malignant transformation can occur. Given the exceptional rarity of this pathological process, much of what is currently understood about this disease comes from case studies. Continued reporting of this pathology will be essential for further development and understanding its clinical and pathologic presentation.

Laparoscopic Treatment of a Pyogenic Hepatic Abscess Caused by Transmural Duodenal Perforation of a Toothpick.

The development of pyogenic hepatic abscess resulting from perforation of the gastrointestinal tract is a rare pathologic finding. It is a condition that can be fatal making early detection and subsequent removal of the inciting foreign body critical to avoid more deleterious sequela. Yet, its initial presentation tends to be nonspecific and typically is only discovered once surgical investigation into the cause of persisting abscess formation is performed. In this study, laparoscopic treatment of a 52-year-old male with a non-resolving hepatic abscess due to transmural gastrointestinal perforation of a toothpick is presented. Although a rare finding, reports of foreign body induced hepatic abscess have recently increased in the world literature, allowing some preliminary efforts in proposing diagnostic characterization. Yet, more case studies will be required to permit validation of these findings making continued reporting of this pathologic process critical.