Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients.

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.

The use of a bioactive skin substitute decreases length of stay for pediatric burn patients.

BACKGROUND: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA). This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children. METHODS: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n = 20). These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy. Standard therapy consisted of application of antimicrobial ointments and hydrodebridement. The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS. Data were analyzed using the student's t test. RESULTS: Data for age, percent TBSA burn and LOS are reported as means +/- SEM. The children who received standard therapy were 2.99 +/- 0.7 years compared with those receiving TransCyte were 3.1 +/- 0.8 years. There was no difference between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 +/- 1.4% TBSA versus TransCyte, 12.7 +/- 1.3% TBSA. There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group. Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%). Children treated with TransCyte had a statistically 6 significant decreaed LOS compared with those receiving standard therapy, 5.9 +/- 0.9 days versus 13.8 +/- 2.2 days, respectively (P =.002). CONCLUSIONS: This is the first study using TransCyte in children. The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS. This new approach to pediatric burn care is effective and improves the quality of care for children with burns.

Surgical care in the isolated military hospital.

BACKGROUND: To maintain the health of service members and their families throughout the world, the Department of Defense has established several isolated military hospitals (IHs). The operational environment of IHs is such that illness and traumatic injury requiring surgical intervention is common. This study sought to examine the general and orthopedic surgical experience at an IH to determine whether surgical care could be provided in an effective and safe manner. METHODS: All patients evaluated by the general and orthopedic surgeon at Guantanamo Bay Naval Hospital from October 1, 1998, to April 1, 1999, were included in this study. The following data were retrospectively reviewed: patient demographic data, diagnosis, initial and follow-up care, medical evacuation data, operative procedures, and complications. RESULTS: There were 336 patients who presented for surgical evaluation, resulting in 660 follow-up appointments during the study period. There were 31 medical evacuations (3 emergent). The surgical services performed 122 major operative procedures. There were 58 inpatient admissions. There was 1 death, and surgical complications occurred in 2 patients, for an overall morbidity and mortality of 1.4% and 0.7%, respectively. CONCLUSION: Our data show that an IH is capable of providing surgical care, including care for traumatic injuries, in a safe manner. This is the first study that provides objective evidence that general and orthopedic surgery at an IH can be provided within the standard of care.

Growth-factor enhancement of compromised gut function following massive small-bowel resection.

Our laboratory has shown that epidermal growth factor (EGF) and hepatocyte growth factor (HGF) can improve the function of normal rat small intestine. This study was designed to evaluate the role of these growth factors on the residual small intestine following massive (80%) small bowel resection. Our data demonstrate that EGF and HGF can enhance intestinal substrate absorption and mucosal mass beyond that which occurs with intestinal adaptation. These growth factors may be beneficial in the management of children with short bowel syndrome.

Spleen-preserving pancreatectomy for cystic pancreatic neoplasms.

Cystic neoplasms of the pancreas are an uncommon entity comprising fewer than 1 per cent of all pancreatic neoplasms. The guidelines for management of these tumors, specifically, the extent of resection, are unclear. Formerly, a distal pancreatectomy including the spleen was performed for tumors in the tail of the pancreas. The importance of preserving the spleen has been well documented; however, there are few reports of spleen-preserving pancreatectomy for cystic neoplasms of the distal pancreas. We report two patients who underwent spleen-preserving pancreatectomy for mucinous cystic neoplasms in the tail of the pancreas. Both patients were female, ages 39 and 65 years. Preoperative preparation included administration of vaccinations and subcutaneous somatostatin. Operative technique emphasized division of the splenic artery and vein beyond the tip of the distal pancreas without mobilization of the spleen. The pancreas was transected with a vascular stapler. Fibrin glue was applied to the margin of the pancreas. The operative blood loss, duration of operation, and postoperative hospital stay were 150 and 250 mL, 150 and 180 minutes, and 7 and 9 days, respectively. The pathology revealed both lesions to be mucinous cystic neoplasms. The patients recovered and at 6-month follow-up were without complaints and in good health. Spleen-preserving pancreatectomy is rapid and associated with minimal morbidity. This procedure should be considered in the surgical management of cystic neoplasms in the tail of the pancreas.

Prognostic significance of DNA replication errors in young patients with colorectal cancer.

OBJECTIVE: To determine the DNA replication error (RER) status in young patients with colorectal cancer (CRC), and to compare the clinical and pathologic characteristics of RER-positive and RER-negative cases. SUMMARY BACKGROUND DATA: Recent studies suggest that patients with RER-positive CRC have an improved prognosis. Further data are required to confirm this observation in young CRC patients. METHODS: All patients 40 years of age and younger with CRC admitted to the National Naval Medical Center between 1970 and 1992 were considered for inclusion in the study. After review, 36 patients for whom the original archived pathology specimen could be retrieved served as the study population. The RER status was determined using a previously described polymerase chain reaction-based assay. The clinical and pathologic features and survival data were compared to RER status. RESULTS: RER-positive tumors were found in 17 cases (47%). There was no significant difference in Dukes' stage or histologic grade at the time of diagnosis between patients with RER-positive tumors compared to RER-negative tumors. Patients with RER-positive tumors were found to have an improved prognosis: the 5-year survival probability for patients with RER-positive tumors was 68%, as compared to 32% for patients with RER-negative tumors (p < 0.05). CONCLUSIONS: RER-positive tumors are common in young patients with CRC, and patients with RER-positive tumors have a significantly improved prognosis. Because of their young age, survival data and prognosis play an important role in the overall treatment plan of young patients with CRC. Therefore, knowledge of RER status could affect initial therapy, postoperative chemotherapy, and follow-up.

Influence of luminal hepatocyte growth factor on small intestine mucosa in vivo.

In 1984, a growth factor was identified that stimulated hepatocyte DNA synthesis. This growth factor, referred to as hepatocyte growth factor (HGF), has been shown to enhance growth of intestinal epithelial cells in vitro. Recently, we reported that HGF can increase absorption and intestinal mass when given systemically in an in vivo model. This study was designed to examine if luminally administrated HGF can stimulate intestinal epithelial cell mass and function. Twenty-five young adult Sprague-Dawley rats had catheters inserted into the small intestine and connected to subcutaneously placed osmotic minipumps. The rats were divided into five groups (n = 5 for each group) based on the contents in the osmotic pump: group 1 received normal saline (control); groups 2, 3, 4, and 5 received HGF in increasing doses of 30, 75, 150, and 300 microg/kg/day, respectively. Following a 14-day infusion, [14C]galactose and [14C]glycine absorption was measured in 10-cm segments of mid-small intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were determined for each group. HGF significantly increased galactose absorption at doses of 75 (P < 0.01) and 150 (P < 0.05) microg/kg/day and glycine absorption at doses of 30 (P < 0.05) and 75 (P < 0.01) microg/kg/day. HGF significantly increased DNA content (P < 0.01) at each dose and protein content when given at 30 (P < 0.01) and 75 (P < 0.01) microg/kg/ day. These data demonstrate that luminal administration of HGF can increase intestinal epithelial cell mass and function in vivo. HGF may be clinically useful in patients with inadequate intestinal function.

Hepatocyte growth factor enhances intestinal mucosal cell function and mass in vivo.

Hepatocyte growth factor (HGF), originally known to stimulate hepatocyte DNA synthesis, recently has been shown to enhance growth of intestinal epithelial cells in vitro. However, there have been no studies on the effect of HGF on the function of intestinal epithelial cells in vivo. This study was designed to examine the effect of systemically administrated HGF on intestinal epithelial cell mass and function. Twenty young adult male Sprague-Dawley rats underwent placement of jugular venous catheters connected to subcutaneously placed osmotic minipumps. The rats were divided into four groups based on the contents in the osmotic pump: Group 1 (control, n = 5), normal saline; Group 2 (n = 5), HGF 75 microg/kg/d; Group 3 (n = 5), HGF 150 microg/kg/d; and Group 4 (n = 5), HGF 300 microg/kg/d. After a 14 day infusion, [C14] galactose and [C14] glycine absorption were measured in a 10-cm segment of mid small intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were determined for each group. With all three doses, HGF significantly increased DNA content (P < .01) and protein content (P < .05). HGF also significantly increased galactose absorption (P < .01) with all three doses. Glycine absorption was increased with a dose of 75 (P < .05) and 150 microg/kg/d (P < .01), but not at a dose of 300 microg/kg/d. These data demonstrate that HGF can increase intestinal epithelial cell mass and function in vivo. HGF may be clinically useful in patients with short bowel syndrome.