Our initial experience with laparoscopic cholecystectomy (LC) for symptomatic cholelithiasis has involved 152 patients. Patient age ranged from 17 to 83 years; most were female (78%). Their average weight was 170 pounds (range, 75 to 365 lbs.). Twenty-two per cent had a single gallstone, while 9% had two to three stones and 64% had more than three stones. Exclusion criteria initially included upper abdominal scarring, severe acute cholecystitis, choledocholithiasis, and inability to tolerate general anesthesia. The first two of these are now only relative contraindications with increased experience. Thirteen of the one hundred fifty-two procedures (8.5%) required conversion to an open operation. Average time of operation was 138 minutes. Intraoperative cholangiography was attempted in 78% of cases and was completed successfully in 66% of those attempted. There have been no deaths. The complication rate has been low: 4% major, 0% life-threatening, and 7.2% minor complications. Postoperative analgesic requirements are remarkably low: 36% of patients required no narcotics after leaving the recovery room. Eighty-seven per cent of patients successfully undergoing LC were discharged by the first postoperative day. Most patients resumed normal activities within 1 week after discharge. Laparoscopic cholecystectomy offers the majority of patients with symptomatic cholelithiasis an improved treatment option, resulting in significantly less postoperative pain, hospitalization, and recuperation time.
The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF-β family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1 cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins post-translationally and that this cascade is essential for aggressive breast tumor behavior in vivo. As the MAPK pathway is an important target for treating triple-negative breast cancers, upstream Nodal signaling may represent a promising target for breast cancer diagnosis and combined therapies aimed at blocking ERK pathway activation.
The authors' experience with laparoscopic cholecystectomy (LC) in obese (O, n = 96) and morbidly obese (MO, n = 27) patient groups was compared with that in the normal weight (NW, n = 174) group of patients as well as the whole group (WG). There were no operative deaths. There were no significant differences between groups for any of the following: successful intraoperative cholangiography (WG, 52.2%; NW, 52.9%; O, 51.1%; MO, 55.6%), conversion to open cholecystectomy (WG, 9.6%; NW, 9.2%; O, 10.4%; MO, 11.1%), incidence of major complications (WG, 4.1%; NW, 3.4%, O, 5.2%; MO, 0%), incidence of minor complications (WG, 7.4%, NW, 7.5%; O, 6.3%; MO, 3.7%), and length of hospitalization after successful LC (WG, 1.25 days; NW, 1.31 days; O, 1.16 days; MO, 1.13 days). Duration of operation did not differ except LC in the MO group (136.4 +/- 6.9 minutes) was longer when compared with NW patients (123.0 +/- 2.9 minutes, p less than 0.05). The authors conclude LC is a safe and effective treatment for obese patients with symptomatic cholelithiasis.
Ischemic injury to the rectum is rare owing to its rich vascular supply, and is seldom seen in clinical practice. Risk factors include major vascular occlusive disease, disruption of collateral circulation, and low flow state. It is of paramount importance to diagnose this entity early in its course. Although CT scan can suggest the diagnosis and identify other causes of clinical deterioration, colonoscopy remains the key test in diagnosing and determining the extent of ischemic change. Endoscopic findings and the overall clinical picture determine patient management. Treatment is nonoperative for nongangrenous ischemic proctocolitis, whereas surgery is necessary for gangrenous, transmural rectal ischemia. Over a 20-year period, a retrospective review of cases of acute rectal ischemia were analyzed. Aortoiliac occlusive disease accounted for nearly one-half the cases (7/15), and 40 per cent (6/15) was secondary to a low flow state. In our series, two-thirds of the cases involved transmural necrosis of the rectal wall (40% mortality) and the remaining one-third presented with patchy ischemic changes (20% mortality).
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