Myogenous sarcoma of the gallbladder with a hemangiopericytomatous pattern.

Primary sarcoma of the gallbladder is a very rare neoplasm, and there are few instances of its diagnostic and therapeutic management. We describe a 66-year-old male patient with a sarcoma of the gallbladder. He initially underwent a laparoscopic cholecystectomy, converted to an open procedure. Histology showed a primary sarcoma of the gallbladder (NOS). A relaparotomy, with resection of the cystic stump, anatomical hepatic resection of the fifth segment, including the bed of gallbladder, and lymphadenectomy was performed a few days later. The two surgical interventions were done with no major complications, and a radical resection status was achieved. Histological investigation revealed a malignant mesenchymal tumor lesion, which was classified as a myogenous sarcoma with a hemangiopericytomatous pattern. After an 11-month, uneventful, postoperative course, local tumor recurrence was diagnosed. Palliative chemotherapy was scheduled, but the patient died of advanced tumor recurrence 10 days after this diagnosis. Despite a poor overall prognosis, extensive surgical resection is favored for myogeneous sarcoma of the gallbladder; this procedure is based on precise clarification of the histopathological diagnosis, and can be followed by attempts with radiation of chemotherapy if early diagnosis-finding has failed. This approach allowed, in our patient with this rare neoplasm, a remarkable tumor-free survival of almost 1 year.

Laparoscopic cholecystectomy and gallbladder cancer.

Heightened awareness of the possible presence of gallbladder cancer (GBC) and the knowledge of appropriate management are important for surgeons practising laparoscopic cholecystectomy (LC). Long-term effects of initial LC versus open cholecystectomy (OC) on the prognosis of patients with GBC remain undefined. Patients who are suspected to have GBC should not undergo LC, since it is advantageous to perform the en-bloc radical surgery at the initial operation. Since preoperative diagnosis of early GBC is difficult, preventive measures, such as preventing bile spillage and bagging the gallbladder should be applied for every LC. Many port-site recurrences (PSR) have been reported after LC, but the incidence of wound recurrence is not higher than after OC. No radical procedure is required after postoperative diagnosis of incidental pT1a GBC. It is unclear if patients with pT1b GBC require extended cholecystectomy. In pT2 GBC, patients should have radical surgery (atypical or segmental liver resection and lymphadenectomy). In advanced GBC (pT3 and pT4), radical surgery can cure only a small subset of patients, if any. Additional port-site excision is recommended, but the effectiveness of such measure is debated.

Sealing of the hepatic resection area using fibrin glue reduces significant amount of postoperative drain fluid.

AIM: To investigate whether the routine use of fibrin glue applied onto the hepatic resection area can diminish postoperative volume of bloody or biliary fluids drained via intraoperatively placed perihepatic tubes and can thus lower the complication rate. METHODS: Two groups of consecutive patients with a comparable spectrum of recent hepatic resections were compared: (1) 13 patients who underwent application of fibrin glue immediately after resection of liver parenchyma; (2) 12 patients who did not. Volumes of postoperative drainage fluid were determined in 4-h intervals through 24 h indicating the intervention caused bloody and biliary segregation. RESULTS: Through the first 8 h postoperatively, there was a tendency of higher amounts of fluids in patients with no additional application of fibrin glue while through the following intervals, a significant increase of drainage volumes was documented in comparison with the first two 4-h intervals, e.g., after 12 h, 149.6 mL +/-110 mL vs 63.2 mL +/-78 mL. Using fibrin glue, postoperative fluid amounts were significantly lower through the postoperative observation period of 24 h (851 mL +/-715 mL vs 315 mL +/-305 mL). CONCLUSION: For hepatic resections, the use of fibrin glue appears to be advantageous in terms of a significant decrease of surgically associated segregation of blood or bile out of the resection area. This might result in a better outcome.

Effect of intraperitoneal application of an endotoxin inhibitor on survival time in a laparoscopic model of peritonitis in rats.

Gram-negative sepsis due to fecal peritonitis is a hazardous disease with a high percentage having a lethal course. The inflammatory effects are induced by endotoxin release. We performed this study to evaluate the potential of direct intraperitoneal application of an endotoxin inhibitor in a laparoscopic peritonitis model in rats. The human feces specimen was prepared, and a standard fecal specimen (0.5 ml/kg b.w.) was applied via minilaparotomy. The rats were randomized to two studies. First, rats were randomized to three groups to define the survival time: (1) rats without further manipulation; (2) rats with laparoscopic lavage using NaCl; (3) rats with laparoscopic lavage using endotoxin inhibitor. Second, rats underwent the same procedure used in the first part of the study and an additional group with only NaCl lavage without peritonitis was randomized. To evaluate the immunologic or biochemical effects, animals were killed at a standard time of 20 hours until the postmortem examination was established. Interleukins 6 and 10 (IL-6, IL-10), malondialdehyde, and protein carbonyl group levels in plasma and particularly in peritoneal fluid were assayed. The first part of the experiment showed significantly increased survival after endotoxin inhibitor lavage. In the second part, administration of endotoxin inhibitor intraperitoneally caused a significant reduction of IL-6 in the peritoneal fluid, in contrast to that in the other groups. Laparoscopic application of endotoxin inhibitor intraperitoneally thus produced a beneficial effect on survival and reduction of IL-6 in peritoneal fluid. Hence, it is possible to influence the inflammation cascade by causing intraperitoneal endotoxin inhibition.

Web-based data warehouse on gene expression in human colorectal cancer.

Based on biomedical literature databases, we tried a first step for constructing a gene expression "data warehouse" specific to human colorectal cancer (CRC). Results of genome-wide transcriptomic research were available from 12 studies, using various technologies, namely, SAGE, cDNA and oligonucleotide arrays, and adaptor-tagged amplification. Three studies analyzed CRC cell lines and nine studies of human samples. The total number of patients was 144. Out of 982 up- or down-regulated genes, 863 (88%) were found to be differentially expressed in a single study, 88 in two studies, 22 in three studies, 7 in four studies, and only 2 genes in six studies. Eight large-scale proteomics studies were published in CRC, using 2-D-, SDS- or free-flow electrophoresis, involving only 11 patients. Out of 408 differentially expressed proteins, 339 (83%) were found to be differentially expressed only in a single study, 16 in three studies, 10 in four studies, 3 in five, and 1 in eight studies. Confirmation at proteome level of results obtained with large-scale transcriptomics studies was possible in 25%. This proportion was higher (67%) for reproducing proteome results using transcriptomics technologies. Obviously, reproducibility and overlapping between published gene expression results at proteome and transcriptome level are low in human CRC. Thus, the development of standardized processes for collecting samples, storing, retrieving, and querying gene expression data obtained with different technologies is of central importance in translational research.

Low-molecular-weight heparin (reviparin) diminishes tumor cell adhesion and invasion in vitro, and decreases intraperitoneal growth of colonadeno-carcinoma cells in rats after laparoscopy.

BACKGROUND: Metastases, adhesion and invasion of tumor cells involve a cascade of complex phenomena, which potentially can be affected by glycosaminoglycans. We studied the influence of a low-molecular-weight heparin, reviparin, on the intraabdominal tumor growth in rats undergoing laparoscopy. We also studied cytotoxicity, anti-adhesive, and anti-invasive effects of reviparin in vitro using adenocarcinoma cells CC531. METHODS: In vitro assays: Adhesion of 1 x 10(5) CC531 adenocarcinoma cells onto microtiter plates coated with 10 microg/ml collagen type I or 10 microg/ml Matrigel was studied in the presence of 0.55; 1.10 and 2.76 mg/ml reviparin, and compared to saline. The cytotoxicity of 1 x 10(4) adenocarcinoma cells was studied in a similar assay. Transwell dual chambers with polycarbonate filters coated with 100 microg/cm2 Matrigel were used to investigate the effect of 0.55; 1.10 and 2.76 mg/ml reviparin on the invasion of 1 x 10(5) adenocarcinoma cells/ml. In vivo experiments: CC531 adenocarcinoma cells (5 x 10(6) cells/ml) were intraperitoneally applied to Wistar Albino Glaxo rats (n=150, Harlan, Germany) with a median weight of 278 g. The rats were divided into 15 groups with 10 animals in each group, underwent laparoscopy, and 1 ml saline containing 0, 0.5, 2.0, 4.0, and 10 mg reviparin per kg b.w. was introduced for intraperitoneal lavage or s.c. After 21 days the animals underwent an autopsy, and the tumor weight was determined. RESULTS: In vitro experiments: We found a highly significant inhibition of tumor cell adhesion and invasion (p<0.001) by all reviparin concentrations used in the assays. There was no effect of reviparin on the viability of cells in the cytoxicity assay. In vivo experiments: We found that application of 4.0 and 10.0 mg/kg b.w., but not 0.5 or 2.0 mg/kg b.w. significantly (p<0.01) decreased the tumor mass compared to controls, receiving only saline. This effect was most pronounced after the combined i.p. and s.c. application, whereas after a sole i.p. application, only the highest dose of 10 mg/kg b.w. caused a significant inhibition of tumor growth. CONCLUSION: Low-molecular-weight heparin, reviparin, given in combination of i.p. lavage and s.c. injections, significantly diminishes intraabdominal tumor growth of CC531 adenocarcinoma cells in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic cancer surgery.

Value of a protective stoma in low anterior resections for rectal cancer.

INTRODUCTION: Anastomotic leakage is a major problem in colorectal surgery and in particular in operations for low rectal cancer. The present study investigates the question whether a protective stoma can reduce the (clinical and radiologic) anastomotic leakage rate and/or the rate of leakage requiring surgery. METHODS: The investigation took the form of a prospective multicenter study involving 75 German hospitals and was performed between January 1, 1999, and December 31, 1999. A comparison was made of the postoperative results of procedures performed with and those performed without a protective stoma in patients undergoing low anterior rectal resection. In addition, logistic regression using the target criteria, overall anastomotic leakage and anastomotic leakage requiring surgery, was applied. RESULTS: Among the 3,695 operations performed for carcinoma of the rectum or colon, 482 were low anterior resections. In 334 patients (69.3 percent) no protective stoma was constructed, whereas 148 (30.7 percent) received such protection. Age, American Society of Anesthesiologists physical status, and body mass index were identical in both groups. In the group receiving a protective stoma, however, neoadjuvant radiochemotherapy was more common, the tumors were lower-and thus the total mesorectal excision rate higher, the intraoperative complication rate was higher, and the duration of the operation was longer. The differences were all significant. The major criterion (overall anastomotic leakage rate) was identical in the two groups, but the rate of leakage requiring surgery was significantly lower in patients receiving a protective stoma (p = 0.028). The logistic regression revealed that use of a protective stoma is a predictor of protection against anastomotic leakage requiring surgery. The distance of the tumor from the anal verge and the duration of the operation are further predictors. CONCLUSION: The particular benefit of a covering stoma is reduction in the rate of leaks requiring surgery and thus in the severe consequences of an anastomotic leakage.