Shedding-induced gap formation contributes to gut barrier dysfunction in endotoxemia.

BACKGROUND: The intestinal mucosa exhibits high turnover rates with a balance of shedding and the migration of epithelial cells to maintain gut barrier function. Systemic diseases such as sepsis and major thermal injury accelerate the rate of cell shedding, subsequent gap formation, and gut barrier dysfunction. However, the detailed changes of intestinal villi in barrier dysfunction have not been well described. METHODS: In this study, intestinal barrier dysfunctions were induced through the injection of lipopolysaccharide (LPS) in C57BL/6 mice. Intravital images of the small intestine were observed with multiphoton microscopy for cellular dynamics analysis. The changes of epithelial cells shedding, gap formation, goblet cells, and intestinal leaks were observed, calculated, and analyzed. RESULTS: Endotoxemia enhanced chromatin condensation, accelerated migration, and increased the shedding of intestinal epithelial cells compared with the control group. Furthermore, LPS-induced shedding resulted in gap formation and subsequent intestinal leaks. In total, 40% of intestinal leaks were through gaps, and 60% were through paracellular spaces. Although LPS injection significantly increased the leaks in gaps and paracellular spaces, it did not change the percentage of leaks in gaps and paracellular spaces compared with the control group. CONCLUSION: We conclude that endotoxemia causes gut barrier dysfunction by increasing epithelium shedding, gaps, and intestinal leaks. However, the effect of the impairment of local barrier maintenance on the distribution of intestinal leaks in gaps and paracellular spaces is minimal.

Laparoscopic liver resection for hepatocellular carcinoma: intermediate follow-up results.

BACKGROUND/AIMS: Laparoscopic hepatectomy (LH) has gained increased acceptance for the treatment of selected hepatocellular carcinoma (HCC). The technical consideration and long-term follow-up data of LH for hepatocellular carcinoma are limited. The current study presents the experience of 17 LH for HCC with a mean follow-up of 23 months. METHODOLOGY: From April 2003 to December 2005, we successfully performed 17 LH for patients with HCC. Patient demographics, peri-operative parameters and outcomes of the 17 patients were assessed retrospectively. RESULTS: All 17 LH were performed smoothly without conversion to laparotomy. There was no operative mortality, but transfusion and relaparoscopy was required for one patient with internal bleeding 7 days after LH. The mean hospital stay was 10.9 (6-23) days. All but one patient had section margins longer than 1 centimeter. Four patients had tumor thrombi in portal vessels of their resected specimen. During the mean follow up of 23 months, five patients (29.4%) developed recurrence. Four of the recurrences limited in the liver, and one patient had both liver and lung metastasis. No port site or peritoneal metastases were observed. Treatment of recurrence was second resection in one patients and trans-arterial embolization therapy in four other patients. Mean disease-free survival was 19 months. CONCLUSIONS: Laparoscopic hepatectomy is feasible in selected patients with single, smaller and peripherally-located hepatocellular carcinoma. The surgical morbidity and intermediate followup results seem satisfactory.

Preoperative serum placenta growth factor level is a prognostic biomarker in colorectal cancer.

PURPOSE: Increased angiogenesis at the site of the primary tumor in colorectal cancer has been associated with poor prognosis and relapse of disease. We previously demonstrated that the tissue level of placenta growth factor expression was upregulated in colorectal cancer and correlated with disease progression and patient survival. The aims of this study are to examine the prognostic value of serum placenta growth factor, vascular endothelial growth factor, and sFlt-1 and to compare them with the carcinoembryonic antigen levels in patients with colorectal cancer. METHODS: Preoperative serum from 86 patients and serum from 30 healthy controls was included. The levels of sFlt-1, placenta growth factor, vascular endothelial growth factor in the serum were assayed and correlated with the clinical stage results. RESULTS: Serum placenta growth factor, but not vascular endothelial growth factor, increased; sFlt-1 decreased in patients with preoperative colorectal cancer, compared with healthy controls. Higher preoperation serum placenta growth factor levels were associated with higher risk of recurrence. Preoperation serum placenta growth factor, but not carcinoembryonic antigen, was a prognostic indicator in patients with Stage III colorectal cancer. When we use the median level (20.6 pg/ml) of preoperative serum placenta growth factor as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence and survival was 80, 54, 80% and 70, 56, 70%, respectively. CONCLUSIONS: Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.

Initial experience with ABO-incompatible live donor renal transplantation.

The serious shortage of cadaveric organs has prompted the development of ABO-incompatible live donor renal transplantation. We report our experience of the initial two live donor ABO incompatible renal transplants at our hospital. The first patient was a 55-year-old type A female who received a kidney from her AB type husband. The second patient was a 27-year-old type O male who received renal transplantation from his type A father. Preconditioning immunosuppressive therapy in the two patients with tacrolimus, mycophenolate mofetil and methylprednisolone was started 7 days before transplantation. During the period of preconditioning, double filtration plasmapheresis (DFPP) was employed to remove anti-A and -B antibodies. Laparoscopic splenectomy and renal transplantation were performed after the anti-donor ABO antibodies were reduced to a titer of 1:4. Rituximab, a humanized monoclonal anti-CD20 antibody, was administered to the second patient due to a rebound in the anti-A antibody titer during the preconditioning period. Under a tacrolimus-based immunosuppressive regimen, both patients recovered very well without any evidence of rejection. Serum creatinine levels were 1.0 and 1.4 mg/dL at 6 and 3 months after transplantation, respectively. These cases illustrate that with new immunosuppressive agents, DFPP and splenectomy, ABO-incompatible renal transplantation can be successfully conducted in end-stage renal disease patients whose only available live donors are blood group incompatible.

Minimally invasive surgery for gastric stromal cell tumors: intermediate follow-up results.

Laparoscopic wedge resection of the stomach (LWS) has become the treatment of choice for patients with benign gastric tumors. The technical consideration and long-term follow-up data of LWS for gastrointestinal stromal tumors (GISTs) of the stomach are limited. We present our experience of 28 LWSs for gastric GISTs with a mean follow-up of 43 months. From October 1995 to December 2002, we successfully performed 28 LWSs for 29 patients with GISTs of the stomach, and one patient needed conversion to laparotomy because of suspected bowel injury when establishing pneumoperitoneum. Patient demographics, perioperative parameters, and outcomes of the 28 patients were assessed retrospectively. The tumors were located in the upper third of the stomach in 13 patients, in the middle third, in eight patients, and in the lower third, in seven patients. The mean size of tumors was 3.4 +/- 1.6 cm in diameter. The duration of operation ranged from 95 to 390 minutes: 189.6 +/- 79.5 minutes with the stapler method and 194.3 +/- 50.5 minutes with the hand-sewn method (P = 0.8870). No blood transfusion was given in the perioperative period in all cases. Cholecystectomy in three patients and repair of hiatal hernia in one patient were performed during the same operation. The oral intake was restored at the third to fourth postoperative days. The hospital stay ranged from 3 to 11 days (mean, 6.7 +/- 1.8 days). The follow-up period ranged from 12 to 95 months (mean, 43.3 +/- 23.5 months, median 42 months). There has been no evidence of tumor recurrence, including one patient with microscopic invasion of section margin. LWS can be performed safely with a satisfactory remission rate for patients with gastric stromal cell tumors.

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy (LS) has become the treatment of choice for patients with idiopathic thrombocytopenic purpura (ITP) who do not respond to medical treatment. Long-term follow-up data of LS for ITP are scarce. METHODS: From May 1997 to December 2002, we performed 67 LS for patients with ITP. Data were assessed retrospectively. RESULTS: LS was successfully attempted in all 67 patients. There was no surgical mortality. Three postoperative complications (5%) were encountered. The mean operative time decreased significantly from 176.2 minutes in the first 41 cases to 125.2 minutes in the last 26 cases. The mean postoperative hospital stay was 3.2 days. Accessory spleens were found in 3 patients (5%) during the LS. The mean follow-up interval was 23.3 months. The initial response to LS was 83%, and overall remission of ITP was 74%. The preoperative effect of steroid therapy had no significant influence on postoperative remission rate. More significant indicators of LS effectiveness were either an immediate postoperative platelet count surge or an immediate postoperative platelet count >or=100000/microL. CONCLUSIONS: LS can be performed safely with a satisfactory remission rate for patients with ITP who do not respond to medical treatment. Our results indicated that an immediate postoperative platelet count surge and/or an immediate postoperative platelet count >or=100000/microL were positive predictors of long-term remission after LS for ITP.

Profile of hepatocyte growth factor in patients with obstructive jaundice.

BACKGROUND/AIMS: Hepatocyte growth factor is a potent growth-stimulating factor of many kinds of tissue. Hepatocyte growth factor was demonstrated in the blood of various liver diseases, and its concentration was reported to correlate with liver function after partial hepatectomy. In this study, we monitor the dynamics of bile hepatocyte growth factor in patients with obstructive jaundice. METHODOLOGY: In a university hospital, 68 paired blood and bile samples from 42 patients with hyperbilirubinemia were determined with ELISA. The hepatocyte growth factor bile/blood ratio and both daily hepatocyte growth factor clearance and output were calculated for each pair. The correlations between these values with other biochemical parameters were then determined. RESULTS: The blood hepatocyte growth factor concentration correlated positively with serum bilirubin (r = 0.556, p < 0.001) level, whereas bile hepatocyte growth factor concentration, hepatocyte growth factor bile/blood ratio, hepatocyte growth factor clearance and daily hepatocyte growth factor output correlated negatively with serum bilirubin level (p = 0.006, < 0.001, < 0.001 and 0.002, respectively). Similar strong positive correlations also were found to exist between these hepatocyte growth factor measurements and other liver function parameters. CONCLUSIONS: In this study we demonstrated that the hepatocyte growth factor was significantly higher in bile than in blood and that the excretion of hepatocyte growth factor in the bile was decreased in patients with obstructive jaundice. The higher blood hepatocyte growth factor level in patients with obstructive jaundice might be due to decreased hepatocyte growth factor excretion. The higher hepatocyte growth factor level in bile also might explain why liver cirrhosis occurs after prolonged jaundice.

Prognostic factors for hepatocellular carcinoma < or = 3 cm in diameter.

BACKGROUND/AIMS: As surgical morbidity and mortality for hepatocellular carcinoma resection decline, we would like to analyze the possible prognostic factors for small hepatocellular carcinoma after curative resection. METHODOLOGY: A total of 170 patients receiving primary hepatectomies for small hepatocellular carcinoma (< or = 3 cm in diameter) at the National Taiwan University Hospital from December 1987 to February 1997 were enrolled as Group 1. The other 281 patients receiving hepatectomies for hepatocellular carcinoma larger than 3 cm were enrolled as the control group (Group 2). The overall patient and disease-free survival rates were calculated and the possible prognostic factors analyzed. RESULTS: The 1-, 3-, 5-, and 10-year patient survival rates in Group 1 were 89.6, 73.1, 55.7 and 34.0%, respectively. A safety margin > or = 1 cm (p = 0.0283), single tumor (p = 0.0324), and multiple hepatic resection (p = 0.0239) were factors favorable to patient survival by multivariate risk factor analysis. The disease-free survivals for Group 1 were 75.6, 41.4, 25.9 and 19.2% at 1, 3, 5, and 10 years, respectively. Significant factor for better disease-free survival included only euploid DNA content (p = 0.0026). The patient survival and disease-free survival rates of Group 1 were significantly better than those of Group 2. CONCLUSIONS: We conclude that patients with small hepatocellular carcinoma have better prognosis than those patients with larger tumors. Early detection of hepatocellular carcinoma and its recurrence are crucial for both patient and disease-free survival. The only prognostic factors that can be manipulated are the keeping of adequate safety margin and repeated resection for recurrent hepatocellular carcinoma.

Tuberculous peritonitis mimicking peritonitis carcinomatosis: a case report.

UNLABELLED: A 13-year-old girl presented with non-specific symptoms of peritonitis, low grade fever and missed her normal menses. Computed tomography of her abdomen and pelvic cavity showed omental cake and a generalised thickened peritoneum. An elevated serum cancer antigen-125 (CA-125) level of 1248.5 U/ml was also noted and a diagnosis of peritonitis carcinomatosis was first suspected. Diagnostic laparoscopy revealed multiple tubercles over the whole peritoneum and the pathology report described granulomatous nodules with giant cells and epithelioid cells. Culture of the ascitic fluid revealed Mycobacterium tuberculosiswhich resulted in a final diagnosis of tuberculous peritonitis. The patient's fever and abdominal distension gradually subsided after anti-tuberculosis treatment. The serum CA-125 level also decreased significantly to 10.2 U/ml after treatment. CONCLUSION: cancer antigen-125 levels may serve as a potential follow-up marker of disease activity and treatment response in tuberculous peritonitis.

Treatment of centrally located hepatocellular carcinoma with central hepatectomy.

BACKGROUND: For treatment of centrally located hepatocellular carcinoma (HCC), central hepatectomy (including central trisegmentectomy [Couinaud's segments 4, 5, and 8] and anterior segmentectomy [Couinaud's segments 5 and 8]) may have an important advantage (ie, preservation of nontumorous parenchyma) over conventional lobectomy or extended lobectomy. For determination of the efficacy of this technique, we compared the outcomes of patients with HCC who underwent treatment with the central and conventional methods. PATIENTS AND METHODS: In our institute, 52 patients with HCC underwent treatment with central hepatectomy (group 1) and 63 patients with comparable tumor size underwent treatment with conventional major hepatectomy (group 2) from November 1993 to April 1999. Overall patient survival and disease-free survival rates were calculated and analyzed. The possible prognostic risk factors for patient and disease-free survival in group 1 were analyzed. RESULTS: Group 1 had comparable overall patient and disease-free survival rates with those of group 2. Vascular invasion, higher pathology grading, and resection margin less than 1 cm appeared to be the prognostic factors for overall patient survival, and vascular invasion was the only risk factor for disease-free survival. CONCLUSION: Central hepatectomy is a safe and effective operative procedure for the treatment of centrally located HCC. The patient and disease-free survival rates were the same as those of conventional major hepatectomy. Although it is technically more demanding, central hepatectomy preserves more nontumor liver parenchyma, which is important for the survival of those patients with liver cirrhosis.