Wnt/ß Catenin-Mediated Signaling Commonly Altered in Colorectal Cancer.

Colorectal cancer is the second most common cancer in females and the third most common cancer diagnosed in males (Torre et al.1). In 2012, there were about 1.4 million cases and 693,900 deaths due to colorectal cancer worldwide. It is more common in developed countries, and North America, Europe, and Australia have the highest incidence rates. In the United States, adults have a 5% chance of developing colorectal cancer (Cancer of the colon and rectum-SEER stat fact sheets2). Due to the high prevalence of colorectal cancer, understanding the mechanism underlying its initiation and progression in order to find better therapeutic agents will have a high impact in the field of oncology and may improve the treatment of other cancers with shared mechanistic properties. Aberrant Wnt/ß-catenin signaling is a characteristic feature of colorectal cancer development and is the focus of this review.

Laparotomy after using the gastroepiploic artery graft: retrogastric versus antegastric route.

BACKGROUND: Most cardiac surgeons prefer the antegastric route for the right gastroepiploic artery (RGEA) graft. When placed anterior to the stomach, the RGEA pedicle may adhere to the greater omentum, or to the anterior abdominal wall, and may be injured during future abdominal operations. METHODS: To avoid this potentially lethal complication, we prefer to place the RGEA graft behind the stomach and the left lobe of the liver. In our experience with 144 patients in whom the retrogastric route was used, 7 patients required an abdominal operation (2 had cholecystectomy, 2 had a partial colectomy, 1 had repair of paraesophageal hernia, and 2 had repair of abdominal wall complications). There was no need to dissect the RGEA graft in any of these patients. RESULTS: There was no evidence of myocardial ischemia or other complications during or after the operation in any patient. CONCLUSIONS: Based on our experience and the fact that any injury to the RGEA graft may have catastrophic consequences, we strongly advocate the retrogastric route to minimize the risk of injury to the RGEA graft during a subsequent laparotomy.

Traumatic superior mesenteric artery--portal vein fistula.

An interesting and rare case of traumatic superior mesenteric artery-to-portal vein arteriovenous fistula is presented. Initial operative control of the bleeding superior mesenteric artery injury required ligation of the superior mesenteric artery at its origin to prevent exsanguination in an extremely unstable patient with multiple injuries. Early postoperative visceral arteriography documented ligation of the superior mesenteric artery with a proximal superior mesenteric artery-to-portal vein arteriovenous fistula. Percutaneous catheter embolization of the arteriovenous fistula was undertaken successfully at this time. Superior mesenteric artery ligation was surprisingly well tolerated. Major arterioportal fistulas require treatment to prevent long-term complications of intestinal ischemia, portal hypertension, and cirrhosis. Although traditional treatment involves ligation of the arteriovenous fistula and arterial bypass, percutaneous embolization is becoming a viable alternative. Arteriography remains the cornerstone of diagnosis and treatment planning.

Nonpenetrating vascular injury to the subclavian artery.

Blunt subclavian artery injury has been uncommonly reported in the literature. Recent encounter with three such injuries prompted us to review our experience over the past 10 years uncovering only one additional case. These four cases and a review of pertinent literature form the basis for this article. Key clinical issues include a high index of suspicion in patients sustaining major blunt deceleration and rotational or direct injuries to the neck, thorax, and/or upper extremities. Prompt diagnosis remains obscured by the presence of severe associated injuries, the treatment of which requires prioritization. Arteriography is invaluable to elucidate injury because prompt vascular control is dictated by various approaches depending on the location. Expeditious surgical repair is indicated to prevent complications of hemorrhage, pseudoaneurysm, thromboembolism, and/or arteriovenous fistula. Long-term results appear to be good with major morbidity related to associated neurologic, soft tissue, and bony injuries.

Necrosis of the colon as a complication of shock.

Colonic necrosis secondary to hypotension and shock in previously healthy, young patients is a rare occurrence with only ten cases reported in the literature. In all but one instance the necrosis was limited to the right colon. Three additional cases of transmural necrosis involving both the right and left colon following a documented episode of shock are reported. Two cases were related to hemorrhagic shock following trauma and the third case followed a drug overdose with associated hypotension. An episode of hypotension was the common denominator in all cases previously reported. The lowest mean blood pressure in the present series was 35 mmHg. A diagnosis of subtotal colonic infarction was made at laparotomy in these three patients two to nine days after the initial hypotensive episode. Pathologic examination of the excised colon revealed transmural necrosis in all three cases with no evidence of a thrombotic or embolic process accounting for the colonic necrosis. The etiology was felt to be a low flow state within the splanchnic circulation. The data suggests that patients who present with a history of prolonged hypotension and shock are at risk for the development of colonic infarction. Successful management involves early diagnosis and resection of the infarcted colon.

Papillary-cystic neoplasm of the pancreas.

Papillary-cystic neoplasm of the pancreas is a rare tumor which has recently been described as a distinct, clinicopathological entity. Forty-four previously described cases from the literature and an additional 52 cases referred to in a brief abstract are reviewed. An additional case occurring in a 25-year-old woman is reported. This tumor occurs primarily in young women (mean age 23.3 years) and presents as a large abdominal mass (mean size 10.3 cm) in 63% of patients. Treatment is surgical resection of the involved portions of the pancreas and results of treatment are excellent following this form of therapy alone. The tumor appears to represent a low-grade malignancy, possibly of ductal cell origin. Only two patients with recurrences and two patients with metastatic disease have been reported. Surgeons should be aware of this curable pancreatic malignancy as they are most often responsible for the evaluation and treatment of the patient presenting with a large abdominal mass.

Massive degloving injury of the trunk.

A case of massive degloving injury of the perineum, thigh, and buttocks is presented. Hemostasis was achieved with a pneumatic anti-shock garment (PASG), followed by direct suturing of bleeding areas. A colostomy was performed. Initial conservative debridement was followed in ten days by multiple skin grafts. The patient was treated with sodium bicarbonate and mannitol to preclude myoglobinuric renal failure. Intravenous hyperalimentation was also utilized.

Agenesis of the gallbladder: case report and familial investigation.

In this article we report a case of gallbladder agenesis, confirmed at laparotomy, and the subsequent investigation of that patient's family for others with evidence of agenesis. Ultrasonography was chosen as the principal diagnostic tool, and of the eight family members available for study, one was found to have no demonstrable gallbladder by either ultrasonography or oral cholecystography. The overall incidence of gallbladder agenesis is said to approximate 0.01% to 0.04%. However, in each of the four existing familial studies a much higher incidence is noted. With regard to gallbladder agenesis, these data strongly suggest the existence of a familial hereditary trait.

Biliary lipid metabolism in the pregnant baboon.

The serum cholesterol value, bile acid pool size and kinetics as well as lipid composition of gallbladder bile have been studied in seven baboons during nine pregnancies. During pregnancy, the per cent decrease in the average serum cholesterol value ranged from 25.6 to 74.4 per cent, mean 54.5 +/- 14.3 per cent, compared with that of antepartum averages. In seven of the nine pregnancies, chenodeoxycholic acid pool size decreased in the range of 40.1 to 86.6 per cent. In two pregnancies, the pool size of this bile acid was essentially unchanged. Total bile acid pool size also decreased from a mean of 990 +/- 260 milligrams antepartum to 520 +/- 200 milligrams in the third trimester, p less than 0.01. With regard to the cholesterol, phospholipid and bile salt content of gallbladder bile, cholesterol value decreased from an antepartum mean of 19.1 +/- 3.9 to 14.1 +/- 4.5 micromoles per milliliter in the third trimester. As a consequence, the lithogenic index of gallbladder bile decreased during pregnancy. The changes in chenodeoxycholic and total bile acid pool size are qualitatively similar to those reported by other investigators following the administration of estrogens to both baboons and other animal species. In the pregnant baboon, the decrease in pool size and in synthesis rate of bile acids is accompanied by a decrease in the cholesterol content of gallbladder bile. These changes in the lipid content of gallbladder bile are reflected in a decrease in the mean lithogenic index. These data suggest that the baboon may be an inappropriate model for studies of the relationship of pregnancy to cholesterol cholelithiasis in humans. In the baboon, both serum and biliary cholesterol values decrease during pregnancy. In humans, serum cholesterol levels increase during pregnancy. If the content of biliary cholesterol is a reflection of the serum concentration of this lipid, as has been suggested in recent studies, human bile may be more lithogenic during pregnancy. Additional studies are necessary to define the role of gallbladder contractility and bile stasis to gallstone formation during pregnancy.

Toxicity of chenodeoxycholic acid in the nonhuman primate.

Toxicologic aspects of long-term therapy with the gallstone-dissolving agent, chenodeoxycholic acid (CDC) are under study in the baboon. Eighteen animals, subdivided into low (20 mg. per kilogram per day), incremental (18 to 38 mg. per kilogram per day), and high (38 mg. per kilogram per day) dose groups were fed CDC daily for 8 to 15 months. During that period they maintained on appearance of excellent, unchanged health and behavior indistinguishable from that of eight control animals. However, 15 of the 18 CDC-fed animals showed significant elevations of monthly serum glutamic pyruvic transaminase-serum glutamic oxalacetic transaminase determinations, and 14 of the 18, from all dose groups, developed significant focal histologic changes in serial liver biopsies. Histologic changes are similar to those described for lithocholic acid toxicity and correlate with an elevated percentage of chenodeoxycholic acid and, particularly, with lithocholic acid (8 to 14 percent) in gallbladder bile of the CDC-fed animals. A few CDC-fed animals showed histologic changes without enzymatic changes and vice versa. To date none of the focal hepatic lesions appears irreversible; it is too early to determine whether continued CDC feeding results in progression, stabilization, or regression of changes. More intensive surveillance of human subjects receiving chenodeoxycholic acid is indicated.