Perforated Colon Cancer Associated With Post-operative Recurrent Bowel Perforations.

Colon perforation is a major life-threatening condition associated with high morbidity and mortality, which often develops secondary to complicated diverticulitis and, less commonly, colon cancer. We describe the case of a 51-year-old female who had perforated colon cancer with concurrent diverticulosis. Based on history, physical exam, laboratory, and computed tomography (CT) findings on initial presentation, the patient was diagnosed with acute complicated diverticulitis. Despite medical treatment, the patient's condition worsened, warranting exploratory laparotomy and a left hemicolectomy with transverse end colostomy creation. Surgical pathology revealed stage IIIC colon cancer without evidence of diverticulitis. The patient underwent eight cycles of adjuvant chemotherapy with FOLFOX (folinic acid, fluorouracil, and oxaliplatin). Over the next year, the patient experienced recurrent bowel perforations requiring repeated surgeries. Perforations were identified in both the small and large bowel on different occasions. Even though neither presented with a clear etiology, possible ischemic, infectious, erosive, and iatrogenic etiologies were on the differential. Our case exemplifies the mounting complications we should be wary of when performing repeated invasive abdominal operations.

Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission.

The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that following icv FGF1 injection, hypothalamic signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family, is induced for at least 24 h. Further, we show that this prolonged response is required for the sustained antidiabetic action of FGF1 since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, fails to mimic the sustained glucose lowering induced by FGF1. These data identify sustained activation of hypothalamic MAPK/ERK signaling as playing an essential role in the mechanism underlying diabetes remission induced by icv FGF1 administration.