Ranitidine: differential effects on gastric bleeding and mucosal damage induced by aspirin.

This study investigated the influence of ranitidine on mucosal injury and gastric bleeding in 20 normal volunteers taking 600 mg aspirin q.d.s. This study was a double-blind placebo controlled crossover study comparing ranitidine, as 150 mg b.d., 300 mg q.d.s. and 600 mg b.d. with placebo. Gastric mucosal injury was assessed at unsedated endoscopy by counting haemorrhagic and non-haemorrhagic erosions; bleeding was measured in gastric washings. Aspirin alone increased mucosal injury from 0 to 11.4 erosions (mean, P < 0.01) and bleeding from 1.77 to 9.11 microliters blood/10 min (mean P < 0.001). Ranitidine prophylaxis reduced bleeding to 5.34, 3.18 and 3.47 microliters/10 min with 150 mg b.d., 300 mg q.d.s. and 600 mg b.d. respectively (overall effect of ranitidine P < 0.001) and also reduced haemorrhagic erosions though it had no effect on the total number of erosions. Ranitidine is effective at reducing aspirin-induced gastric bleeding and whilst not reducing aspirin-induced gastric erosions, it does reduce the number that appear haemorrhagic. Ranitidine may have a role in the prophylaxis of aspirin-induced gastric bleeding.

A simple and inexpensive preparation of [(51)Cr]-MAA particles.

The feasibility of preparing [(51)Cr]-MAA was investigated using an MAA cold kit and commercially available sodium [(51)Cr]chromate solutions. Of different conditions tested, the best required an addition of a low level of sodium dithionite to achieve a radiolabeling efficiency of 44%. The product was purified by centrifugation to give [(51)Cr]-MAA with 99 +/- 1% radiochemical purity (RCP) comprised of >94% radioactive particles >10 microm, and resulted in a rat biodistribution with >80% in the lungs. [(51)Cr]-MAA is inexpensive, easily and conveniently prepared by this procedure.

The effect of lavage on intraabdominal cell burden.

BACKGROUND: Abdominal lavage is a common surgical practice, but few studies have been conducted to assess its efficacy at removing cells from the abdominal cavity, particularly during laparoscopic surgery. METHODS: After three 12-mm trocars were inserted into six female 30-kg pigs at the umbilicus left and right iliac fossae, the abdomen was insufflated with carbon dioxide. The pelvis of each pigs was injected with 6 million radiolabeled LIM 1215 cells. Then the abdominal cavity was irrigated with either 500 ml 0.9% saline, 500 ml 10% betadine solution, or 1 L 0.9% saline. A maximum of 5 L of solution was used for each animal. The lavage fluid was suctioned into separate containers after each aliquot, and each container was measured for radioactivity. RESULTS: Significantly greater numbers of cells were removed by lavage by the first to third lavage cycle; however, after four lavage cycles, relatively few cells were removed by each further cycle. No difference was observed between 500-ml and 1-L aliquots. Additionally, the mechanical efficacy of 0.9% saline and 10% betadine solution appeared similar. CONCLUSION: These findings suggest that optimal lavage consists of four irrigation/suction cycles utilizing 500-ml aliquots.

Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy.

BACKGROUND: We designed this study to determine whether hematogenous spread has a role in the etiology of port site metastases following laparoscopic surgery. METHODS: The study design had two parts. In experiment 1, two groups (n = 30) of male Dark Agouti rats were studied. Under general anesthesia, the first group (20 rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the internal jugular vein and a further 15-mins period of insufflation. The laparoscopic ports were then removed, and the wounds were closed and marked. In the second group (n = 10), the procedure was identical except that a 2.5-cm midline laparotomy was performed 15 mins after the commencement of anesthesia and insufflation was not used. The laparotomy was closed in two layers. In experiment 2, one group (n = 4) was studied. The study protocol was identical to the first laparoscopic group except that a larger number of 106 DAMA cells were injected. All rats in both experiments were killed 15 days later, and the injection site, laparoscopy wounds, and laparotomy wound were examined histologically by a blinded histopathologist. RESULTS: In experiment 1, one port site tumor was detected in the laparoscopic group and no wound metastases were found in the laparotomy group. Postoperative weight loss was significantly less in the laparoscopic group (p < 0.001). In experiment 2, no port site metastases were detected. CONCLUSION: Although hematogenous spread is a possible mechanism in the development of port site metastases, judging from the low number of port site metastases in this study as compared to previous reports using this tumor model, this mechanism is unlikely to be a major contributor to the problem of wound metastasis following laparoscopy.

Variables in the spread of tumor cells to trocars and port sites during operative laparoscopy.

BACKGROUND: Port-site recurrences have delayed the uptake of laparoscopic colectomy, but the etiology of these is incompletely understood. These studies were designed to investigate variables such as the size of the tumor inoculum and the volume and pressure of the insufflated gas during operative laparoscopy that might affect the deposition of these cells in relation to trocars and port sites. METHODS: Radiolabeled human colon cancer cells were injected into the peritoneal cavity of pigs. Three trocars were inserted, and the abdomen was insufflated with carbon dioxide. The movement of cells within the abdomen was traced on a gamma camera. After 2 h, the trocars were removed and the port sites excised. Two studies were performed. In the first study, tumor inocula were varied from 1.5 x 10(5) to 120 x 10(5). In the second study, insufflation pressure was varied, with pressures 0, 4, 8 and 12 mmHg were studied. RESULTS: When larger tumor inocula were injected, the contamination of both trocars (p = 0.005, Kendall's rank correlation) and trocar sites (p = 0.04, Kendall's rank correlation) increased. The deposition of cells on a trocar site was linked to contamination of its trocar (p = 0.03, chi-square), but the contamination of trocars did not always result in trocar-site contamination (p = 0.5, chi-square). Increased volumes of gas insufflation caused increased intraabdominal movement of tumour cells (p = 0.01, Kendall's rank correlation), although this did not lead to greater contamination of trocars or port sites (p = 0.82, Kendall's rank correlation). Decreased insufflation pressures resulted in increased contamination of trocars and port sites (p = 0.01, Kendall's rank correlation). CONCLUSIONS: If clinical situations parallel this study, strategies such as increasing insufflation pressure, reducing episodes of desufflation and gas leaks, and using frequent intraabdominal lavage may help to reduce the numbers of viable tumor cells displaced to port sites during laparoscopic surgery for intraabdominal malignancy. This may reduce the rate of port-site metastases.

Experimental study of the material composition of laparoscopic ports on tumour cell adherence.

BACKGROUND: Laparoscopic resection of intra-abdominal malignancies has yet to be widely adopted, partly because of concerns over the possible increase in the rate of port-site metastasis. The aetiology of these is unclear, but the laparoscopic instrumentation used may influence the deposition of tumour cells at the port sites during operation. An in vitro model to examine tumour cell adherence to laparoscopic ports and to port sites was developed to examine this hypothesis. METHODS: A pilot study (study 1) was performed in which six smooth plastic, six ribbed plastic and six metal ports were introduced through the shaved abdominal wall of a cadaveric sheep and suspended in a water-bath containing radiolabelled LIM 1215 human colonic cancer cells for 30 min. Radioactivity on both ports and port sites was measured and the number of cells adherent to each structure was calculated. The study was expanded to include a further 36 smooth plastic ports and 36 metal ports (study 2). RESULTS: In study 1 metal ports were found to have significantly more adherent cells than plastic ports (P = 0.004), as did ribbed ports when compared with smooth ports (P < 0.05). In study 2 increased numbers of cells were again detected on metal ports (P < 0.001) when compared with plastic ports. Significantly greater numbers of cells were also detected on the sites through which metal ports had passed than on sites through which plastic ports had passed (P = 0.03). CONCLUSION: In this model, the use of metal ports as opposed to plastic ports resulted in increased deposition of tumour cells on both ports and port sites.

Experimental study of peritoneal blood flow and insufflation pressure during laparoscopy.

BACKGROUND: Port-site metastases after laparoscopic surgery may occur with greater frequency than would be expected following open resection of intra-abdominal malignancies, but the causal mechanism for this is incompletely understood. The possibility that insufflation may increase peritoneal blood flow producing a wound environment conducive to the formation of metastases was investigated. METHODS: The effects of insufflation gas type and pressure were studied in 30-kg female pigs. Pigs were divided into five groups, which were subjected to insufflation at 12 mmHg pressure with helium, insufflation at 12, 8 or 4 mmHg pressure with carbon dioxide, or laparotomy. A microsphere technique utilizing two distinct radiotracers, 99mTc-labelled macroaggregated albumin (MAA) and 51Cr-labelled MAA, was used to study blood flow to the peritoneum, liver and kidneys. RESULTS: Insufflation with carbon dioxide or helium gases had no effect on renal (P < 0.09) or hepatic blood flow (P = 0.54). However, insufflation significantly increased peritoneal blood flow when carbon dioxide (P < 0.05), but not when helium (P = 0.99), was used as the insufflating gas. CONCLUSION: These data suggest that blood flow within the peritoneum is influenced by insufflation with carbon dioxide. It is conceivable that such hyperaemia could increase the propensity for implanted tumour cells to metastasize in these sites following laparoscopy.