Targeting Mitochondrial Bioenergetics in Liposarcoma

Well-differentiated/dedifferentiated liposarcoma (WD/DD LPS) is a common subtype of soft tissuesarcoma in adults. Our understanding of this disease is lacking and treatment options are limited. First, by investigating tumor metabolomics, we identify asparagine (Asn) as a fundamental purpose for mitochondrial respiration in WD/DD LPS. Asn promotes mTORC1 activity to support tumor growth. Depleting Asn by combining mitochondrial complex I inhibition with asparaginase holds therapeutic potential. Next, we characterize WD/DD LPS beyond histological classification by defining mechanisms of dysregulation in mitochondrial dynamics. WD LPS displays low MAPK signaling activity, elongated mitochondrial morphology, and high mitochondrial respiration. Whereas DD LPS displays high activation of MAPK signaling, which promotes activation of DRP1, fragmentation of mitochondria and a glycolytic phenotype. This shift in mitochondrial bioenergetics promotes tumor growth. Trametinib represents a novel therapeutic approach to target this adaptation. Moreover, Trametinib synergizes with chemotherapy, including agents Pazopanib and Palbociclib, further expanding its clinical potential. DRP1 expression may also serve as a prognostic biomarker, associating with worse survival. Altogether, these findings reveal several adaptations in mitochondrial bioenergetics that provide opportunities for targeted therapy in patients with WD/DD LPS

Potential link between post-acute ischemic stroke exposure to hypoglycemia and hemorrhagic transformation

Hemorrhagic transformation is a severe complication of acute ischemic stroke owing to its limited treatment options and poor prognosis. In the last decade, the rates of hemorrhagic transformation incidence have been associated with blood glucose levels. In particular, hyperglycemia at the time of admission has been associated with increased rates of hemorrhagic transformation in acute ischemic stroke patients. Recent pilot clinical trials have attempted to use intensive insulin therapy during stroke treatment to reduce the severity of cerebral infarction and possibly alleviate the risk of hemorrhagic transformation. However, the results of these studies have shown no clear clinical benefit. In addition, intensive insulin therapy has increased rates of hypoglycemia which may be associated with larger infarct growth. We hypothesize that hypoglycemia, similarly to hyperglycemia, is a risk factor for worse outcomes in acute ischemic stroke by promoting hemorrhagic transformation. This review serves to call attention to patterns present within intensive insulin therapy trials and shed light into the pathophysiological effects of hypoglycemia. It is critical that efforts be directed toward the prevention of hemorrhagic transformation by optimizing insulin therapy during the treatment of acute ischemic stroke

Large, extra-abdominal leiomyoma of the round ligament with carneous degeneration

Round ligament tumours represent a rare entity that can present similarly to an incarcerated hernia. Basic understanding and appropriate preoperative management is imperative in order to differentiate between the two diagnoses. Leiomyoma is the most common type of round ligament tumour. It is associated with oestrogen exposure and is more common in the presence of uterine leiomyomas. Here we discuss a 68-year-old woman who presented with a palpable left inguinal mass that progressively grew in size, associated with pelvic pressure and discomfort. On surgical resection, the mass was found to be derived from the round ligament at the entrance of the external inguinal ring. Pathology confirmed a round ligament leiomyoma, measuring 25×9×8.5 cm. This case is the largest round ligament leiomyoma recorded to date and the first to exhibit carneous degeneration. A review of the current literature is also provided

Severe hypertriglyceridemia presenting as eruptive xanthomatosis

Eruptive xanthomatosis is described as the sudden eruption of erythematous yellow papules in the presence of hypertriglyceridemia, often associated with serum triglyceride levels above 2000 mg/dl. Severe hypertriglyceridemia can be caused by primary genetic mutations, secondary chronic diseases, or a combination of both. Uncontrolled diabetes mellitus is a known risk factor. It is imperative for physicians to be aware of eruptive xanthomatosis as a warning sign for severe hypertriglyceridemia due to the underlying risk for the potentially fatal complication of acute pancreatitis. Herein, we discuss a case of a 52-year-old man with uncontrolled diabetes mellitus who presented with eruptive xanthomata and a triglyceride level of 7157 mg/dl, the highest recorded value in the absence of acute pancreatitis, with a remarkable response to drug therapy. A review of the literature is included to discuss the clinical relevance and appropriate treatment of this disease entity

Management of small bowel obstruction and systematic review of treatment without nasogastric tube decompression

BackgroundSmall bowel obstruction (SBO) is common and its management has evolved in recent years.Study designThe literature describing adhesive small bowel obstruction (aSBO) treatment was reviewed, and a formal systematic review was performed to identify publications reporting results of aSBO treatment without NGTs.ResultsThe annual rate of hospital admission for SBO in the US has increased, with 340,100 admissions in 2019 alone. SBO is usually treated with bowel rest, intravenous hydration and NGT placement. In recent years, water soluble contrast (WSC) has been used as a cathartic to simulate bowel function and may reduce hospital length of stay (HLOS) by 1.95 days (95%CI 0.56-3.3). There were 3 articles of the initial 1650 screened that reported outcomes of SBO treatment without NGTs. These articles included 759 patients, of whom 272 (36%) with aSBO were managed successfully without NGTs. When comparing outcomes to patients who did receive NGT decompression, there were no significant differences in operative rates (28.6% v 16.5%, risk ratio 1.34, 95% CI 1.0, 1.8). Mortality and rates of bowel resection were also not affected by NGT decompression (risk ratio 1.98, 95% CI 0.43, 9.10 and risk ratio 1.56, 95% CI 0.92, 2.65, respectively).ConclusionSBO is a common disease process with increasing annual incidence. Use of WSC stimulates the bowel and may reduce HLOS. Modern aSBO treatment protocols should include NGT decompression with consideration of WSC administration. Selection of patients for treatment without NGT decompression requires further investigation

Treating Small Bowel Obstruction Without Nasogastric Tubes

There are 860,000 patients hospitalized every year for small bowel obstruction. Most patients are treated with placement of a nasogastric tube, intravenous hydration and bowel rest. However, nasogastric tubes are extremely painful in patients generally prefer to avoid them if at all possible. A number of patients present with bowel obstruction who do not have active vomiting and may be treated without nasogastric tubes. It is not clear how often this is done and the literature supporting this practice appears to be limited. We intend to perform a prospective clinical trial evaluating the need of nasogastric tubes for the treatment of small bowel obstruction before doing so would like to perform a systematic review of the literature on this topi

Inflammatory fibroid polyp of the gastric antrum presenting as hypovolemic shock: Case report and literature review

Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the submucosa of the gastrointestinal tract, and represent less than 0.1% of all gastric polyps. They are most commonly localized to the gastric antrum, small intestines and recto-sigmoid colon. IFPs are most commonly found incidentally upon endoscopic evaluation in the absence of symptoms. Presenting symptoms depend on the location of the tumor, although polyps located in the stomach most commonly present with epigastric pain and early satiety. Classic histologic features include perivascular onion skinning of spindle cells with an abundance of eosinophilic infiltration. The prompt diagnosis and management of IFP is essential due to its underlying risk for intussusception, outlet obstruction and acute hemorrhage. In addition, recent evidence has shown that IFP is driven by an activating mutation in the platelet derived growth factor receptor alpha ( PDGFRA ) gene, suggesting a neoplastic etiology. Herein, we discuss a case of a 65-year-old woman with an inflammatory fibroid polyp of the gastric antrum who initially presented with early hypovolemic shock and melena. Diagnosis was made by endoscopic visualization, biopsy and immunohistochemical analysis

Carcinosarcoma of the hand

Carcinosarcomas are rare malignant tumors derived of both epithelial and mesenchymal elements. Herein, we report an elderly man originally diagnosed with a squamous cell carcinoma of the hand. Upon excision, the tumor was found to be a more aggressive carcinosarcoma. Immunohistochemical stains revealed that the sarcoma component of the lesion was vimentin positive, whereas the primary carcinoma tumor cells were positive for p63 and CK903. Both components were negative for CD34 and D2-40. This tumor was found to have angiolymphatic invasion and eventually metastasized to the axillary lymph nodes and lungs