Description of a novel approach for intraperitoneal drug delivery and the related device.

BACKGROUND: Two significant limitations of intraperitoneal drug therapy are limited drug distribution and poor penetration into peritoneal nodules. A possible solution is the application of the so-called "therapeutic pneumoperitoneum," taking advantage of the gaseous nature and the pressure of capnoperitoneum during laparoscopy. Our objective was to develop a device able to apply such therapeutic pneumoperitoneum. METHODS: The technology presented here is a spraying device and can be introduced through a trocar. It is driven by mechanical pressure and consists of an injector, a line, and a nozzle. An in vivo experimental study was performed in five pigs. A transvaginal cholecystectomy was performed. At the end of the procedure, a standard dose of methylene blue was sprayed/infused into the abdominal cavity for 30 min (4 test animals w/therapeutic pneumoperitoneum (12 mmHg CO(2)) and 1 control animal w/conventional lavage (2 l intra-abdominal volume with extracorporeal circulation)). At the end of the procedure, all animals were autopsied and the peritoneum was analyzed. Outcome criteria were: (1) drug distribution (as assessed by the stained peritoneal surface at autopsy), and (2) diffusion into the peritoneum (presence or not of macroscopic staining of the outer aspect of the peritoneum immediately after surgery). RESULTS: Stained peritoneal surface was larger after aerosol application compared with peritoneal lavage, and staining more intense. Hidden peritoneal surfaces and the anterior abdominal wall were stained only in the aerosol group. In contrast to peritoneal lavage, the outer aspect of peritoneal membrane was immediately stained after pressurized spraying. CONCLUSIONS: This device and the related approach significantly improve both distribution and penetration of a test substance into the peritoneal cavity in a large animal model. This might be a significant progress in treating intraperitoneal disease, in particular peritoneal carcinomatosis.

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.

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.

Expression and functional proteomics studies in colorectal cancer.

Cell dysfunction results from multiple rather than from single gene interactions in the majority of colorectal cancers (CRC). Proteins, not mRNA, are the functional molecules in the cell, and the relationship between gene expression measured at the mRNA level and the corresponding protein level is not linear. Current proteomics tools allow for the determination of post-translational modifications, and hence the presence of protein isoforms--some of them being disease-relevant. Thus, proteomics approaches are a welcome complement to traditional genetic approaches. In CRC, expression proteomics studies were carried out with colorectal cell lines, whole tissue biopsies, and purified epithelial cells. For CRC, two-dimensional electrophoresis reference maps, protein, and membrane protein databases are available on the internet. Functional proteomics studies have been performed to better understand signaling pathways, to characterize the molecular targets of novel drugs, and to identify tumor-associated antigens in CRC. The increasing use of proteomics technologies, when addressing clinical problems, will accelerate the evolution towards personalized medicine in CRC.