This study provides proof of principle that clinical intuition can modestly supplement the accuracy the NEAT model to more accurately predict survival in patients with advanced cancer.

Background: Recent advances underline intestinal inflammation, induced by handling of the gut during surgery, as crucial mechanism in the pathophysiology of postoperative ileus (POI). Macrophages, in the muscularis layer, and mast cells are the key players in the induction of this inflammatory process. Spleen tyrosine kinase (Syk) is an important kinase involved in macrophage activation as well as in mast cell degranulation and therefore inhibition of Syk pathway may represent an interesting therapeutic approach for POI. In the current study, we have evaluated the effect of the Syk-inhibitor GSK143 as potential treatment to shorten POI. Methods: The effect of an oral single dose (3mg/kg, 1.5 hours before surgery) was evaluated in a mouse model of POI, by analyzing gastrointestinal transit and intestinal muscularis inflammation. The in vitro effect of GSK143 (1 and 3 μM) was evaluated on cultured peritoneal mast cells (pMCs) and bone marrow derived macrophages (BMDMs) stimulated with immune complexes with IgE-anti-TNP (40 ng/mL) and LPS (100 ng/ml) respectively. Results: Administration of GSK143 (3 mg/kg) resulted in a serum level of 0.38±0.24 μM 1.5 hours after oral delivery. Treatment with a single dose of GSK143 (3 mg/kg) significantly improved gastrointestinal transit after surgical intestinal manipulated mice compared to placebo (Geometric Center (GC): Placebo, 4.2 ±0.4 vs GSK143, GC; 6.9±0.6). In addition, GSK143 was able to reduce the number of recruited myeloperoxidase (MPO) positive cells (placebo, 187±30 vs GSK143, 44±8, per 0.5mm2), neutrophils (placebo, 4.6x10-5±0.2 x10-5 vs GSK143, 1.7x10-5 ±0.7 x10-5) and monocytes (placebo, 1.6x106±0.4 x10-6 vs GSK143, 0.8x10-6 ±0.25 x10-6) in the muscularis externa compared to placebo. To define the possible target cells affected, GSK143 was tested in vitro on pMCs and BMDMs. Thirty minutes after GSK143 (1 and 3 μM) or vehicle treatment, pMCs degranulation, quantified by assessment of β-hexosaminidase, was induced by immune complexes with IgE-anti-TNP. Interestingly, GSK143 significantly reduced pMCs degranulation compared to vehicle in a dose dependent manner (GSK143 1μM, 62±7.5% and GSK143 3μM, 76±3.3% inhibition vs vehicle). In line, pre-treatment of BMDMs with GSK143 (1 and 3 μM) prior to LPS challenge significantly lowered the expression of IL-6 (21±4% to 31± 3 % inhibition vs vehicle ), TNFα (39±0.8% to 54±0.7% inhibition vs vehicle ), IL1 β (31±1.3% to 39±1.06% inhibition vs vehicle) and CCL2 (33±5.3% to 43±7% inhibition vs vehicle). Conclusion: Pre-treatment with the Syk-inhibitor GSK143 attenuates intestinal inflammation and consequently restores gastrointestinal transit in a model of POI. In vitro data suggests that both macrophages and mast cells are targeted by GSK143. These findings strongly suggest that Syk inhibition may be a new therapeutical tool to shorten POI.

An 82-year-old black woman with a history of hepatocellular carcinoma presented with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm polypoid mass at the level of the ascending colon with evidence of active bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor, and the patient underwent an ileocolectomy. The serosal side of the colonic lesion was free from tumor, and there was no peritoneal implantation, direct extension, or lymph node involvement. This case represents an extremely rare presentation of metastatic hepatocellular carcinoma.

Acute liver failure has been reported as a frequent complication of transarterial chemoembolization (TACE). We prospectively evaluated the adverse effects and biochemical changes of TACE. From 10/95 to 9/96, 35 patients with hepatic malignancies were evaluated for TACE. Fifteen patients (9 male and 6 female) received 23 treatments. Ten of 15 patients had hepatocellular carcinoma, and 5 had metastatic tumors. Treatment exclusion criteria included advanced liver disease, hepatic vascular thrombosis, and severe comorbidity. TACE consisted of intra-arterial infusion of a mixture of doxorubicin, cisplatin, and mitomycin followed by embolization. Clinical symptoms and laboratory studies were monitored following treatment. Technical success was achieved in all patients. Adverse symptoms were transient, and most resolved within 1 week. Changes in hepatic, renal, and hematologic function were temporary and returned to pre-TACE levels by 1 month. None developed acute liver failure. The mean hospital stay was 3 days. Ten of 13 patients had a significant decrease in baseline tumor markers. The actual survival was 93 per cent with a median follow-up of 10 months. TACE can be performed safely in patients with hepatic tumors. The adverse effects can be anticipated and easily managed.

Although elderly patients are accounted for in all large series of major hepatic resections, the role of age as a determinant of outcome remains unclear. At Cedars-Sinai Medical Center, we review a series of 20 major hepatectomies for neoplasia performed in patients older than 66 years of age (4 of them > or = 80 years old) over a 5-year period. A retrospective comparison was conducted with a group of 22 hepatectomies for malignancy performed in 20 patients younger than 59 years of age during the same time period. The younger group had a significantly greater degree of liver resected (12 trisegmentectomies vs 3). Although one operative death (5% mortality) was observed in the elderly group, no statistically significant difference was noted, when compared to the younger group (Chi-square, P = 0.48). Likewise, no significant difference in the complication rate (20% vs 33%) was noticed (Chi-square, P = 0.8). Severe postoperative liver dysfunction was present in 2 cases (10%) in the elderly group and one (4%) in the younger group. These patients underwent a right trisegmentectomy (TS). Nine patients from each group were resected without red blood cell transfusion. We conclude that major hepatic resection in elderly patients without severe comorbid disease is a safe procedure that is not associated with an increased perioperative morbidity or mortality rate.

Choledochal cyst is a rare congenital abnormality of the biliary tract characterized by dilatation and stasis. Cyst excision is now preferred to internal drainage because of the predilection for development of cancer in the unresected cyst wall. We report on four patients who required reoperations for complications of prior cystoenteric drainage from 14 to 21 years after the original operations. Gastrointestinal bleeding from cyst ulceration as occurred in one patient is heretofore unreported. This reoperative experience emphasizes the importance of cyst excision as primary therapy and underscores these principles: 1) The spectrum of complications, including infection, pancreatitis, cancer, and bleeding may occur with or without intracyst and ductal stones; 2) Radical operative procedures may be required for treatment of the complications; 3) Despite these, cholangiocarcinoma has a dismal prognosis; 4) Patients whose cysts remain unexcised require meticulous lifelong scrutiny and strong consideration for planned reoperation at the time of the first complication.

Traumatic perforations of the left colon and rectum are most frequently managed by procedures that include the formation of a colostomy. Primary repair without colostomy is much less commonly employed. We report nine patients with traumatic perforations of the left colon and rectum treated with the intracolonic bypass tube (ICBT) without concomitant colostomy. In all these patients we believe the standard treatment would have included fecal diversion. Four patients sustained blunt trauma and five sustained penetrating trauma. Healing of the colonic anastomosis occurred in all cases, and the ICBTs were passed per rectum between the tenth and nineteenth days postoperatively. On the basis of this study, we conclude that the ICBT has a role in the treatment of selected injuries of the left colon and rectum as a safe means of avoiding a colostomy.

Fifty-two patients with radiation enteropathy secondary to radiation for abdominal or pelvic malignant neoplasms are described. This series (1977 to 1984) is compared with a series of 50 patients from the same institution over an earlier period (1961 to 1977). Intestinal obstruction was the principal complication in both series; 96% of the patients underwent either intestinal resection or anastomotic bypass of the affected segment. Changes that have occurred since the last report are as follows: changes in source of radiation energy (linear accelerator); less evidence of mucosal damage; increased serosal reaction ("serosal peel"); and increased use of elemental diets, parenteral nutrition, and long intestinal tubes in surgical management. Since postoperative radiation injury occurs most frequently in the pelvis, new developments for the exclusion of small bowel from the pelvis during radiation are reviewed. Changes in fractionation of radiation dosage should also be considered in patients with enteric symptoms during radiation therapy.