Miguel Pera

Influence of postoperative acute-phase response on angiogenesis and tumor growth: open vs. laparoscopic-assisted surgery in mice.

Inflammatory responses and tumor growth are increased after laparotomy compared with laparoscopy in some animal models. Proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) upregulate the expression of vascular endothelial growth factor (VEGF). Our aim was to investigate the influence of postoperative inflammatory responses on angiogenesis and tumor growth. 5 Χ 106 B51LiM cells were injected into the cecal wall of Balb/c mice. After 2 weeks, the animals were randomized into the following three groups: open cecectomy (OC), CO2-laparoscopic-assisted cecectomy (LC), and helium-laparoscopic-assisted cecectomy (LH). On postoperative day 12, the mice were killed. Tumor load scores and weight were significantly greater after laparotomy than after laparoscopy. Serum IL-6 levels 6 hours after surgery (OC: 4157 ± 1297 pg/ml vs. LC: 2514 ± 1417 pg/ml vs. LH: 2255 ± 1714 pg/ml) and VEGF levels on postoperative day 12 (OC: 231 ± 125 pg/ml vs. LC: 45 ± 9 pg/ml vs. LH: 49 ± 8 pg/ml), measured by enzyme-linked immunosorbent assay, were significantly higher in the laparotomy group. Microvessel density was also significantly higher in the OC group (OC: 34.3 ± 11.5 vs. LC: 15.5 ± 12.5 vs. LH: 18.5 ± 11.9). There was a positive correlation between IL-6 and VEGF postoperative serum levels (rho = 0.67; P < 0.001). We concluded that increased systemic levels of proinflammatory cytokines and VEGF are associated with increased angiogenesis and tumor growth after laparotomy compared to laparoscopy in mice.

Enhancing release of peptide yy after near-total proctocolectomy: jejunal pouch vs. ileal pouch-distal rectal anastomosis

Reconstructing the enteric tract after near-total proctocolectomy by interposing a jejunal pouch between the distal ileum and the distal rectum slows small intestinal transit and decreases the number of stools per day compared to a conventional ileal pouch-distal rectal reconstruction. Our hypothesis was that the jejunal pouch operation brings about these results by protecting the ability of the ileal mucosa to secrete peptide YY, thus augmenting the hormonal ileal brake on small intestinal transit and decreasing the stool frequency. In five jejunal pouch dogs and five ileal pouch dogs, more than 6 months after the operation, serum peptide YY concentrations were determined before and at 30-minute intervals for 180 minutes after a standard meal. Fasting serum concentrations of peptide YY, measured by radioimmunoassay, were greater in jejunal pouch dogs (mean ± SEM, 1340 ±143 pg/ml) than in ileal pouch dogs (804 ±52 pg/ml; P <0.01). Postprandial peptide YY concentrations in jejunal pouch dogs were also greater at 30 minutes (jejunal pouch = 1524 ±131 pg/ml, ileal pouch = 913 ±67 pg/ml; P = 0.01) and 60 minutes after the meal (jejunal pouch = 1723 ±250 pg/ml, ileal pouch = 1001 ±70 pg/ml; P = 0.05) and peaked sooner (jejunal pouch = 81 ±17 minutes, ileal pouch = 147 ±12 minutes; P = 0.01). We concluded that the jejunal pouch operation results in greater ileal fasting and postprandial secretion of peptide YY than the ileal pouch operation. The greater release may account, in part, for the slower small bowel transit and decreased number of stools after the jejunal pouch operation.

The jejunal pouch as a rectal substitute after proctocolectomy

Our hypothesis was that a jejunal pouch used as a rectal substitute after proctocolectomy would slow enteric transit, delay defecation, and decrease stool frequency compared to an ileal pouch so used. Twelve dogs underwent proctocolectomy; six had a jejunal pouch-distal rectal anastomosis and six had an ileal pouch-distal rectal anastomosis. After recovery, postprandial mouth-to-anus transit was slower in jejunal pouch dogs (253 ±18 minutes [mean ± SEM]) than in ileal pouch dogs (112 ±7.9 minutes; P <0.05). Moreover, jejunal pouch dogs passed only 4.1 ± 0.3 stools during the 12 hours after eating, whereas ileal pouch dogs passed 6.3 ± 0.9 stools (P <0.05). The mean frequency of proximal ileal pacesetter potentials after feeding was less in jejunal pouch dogs (12 ± 0.4 cycles/min) than in ileal pouch dogs (16 ± 0.3 counts/min; P = 0.01), and jejunal pouches had more action potentials (jejunal = 82% ±4.3% of pacesetter potentials had action potentials, ileal = 61% ±3.0%; P <0.05). In contrast, gastric emptying and pouch motility, emptying, mucosal integrity, and bacteriologie and histologic properties were similar in the two groups of dogs. We concluded that the jejunal pouch operation slowed enteric transit, delayed defecation, and decreased postprandial stooling compared to the ileal pouch operation.

Bile acid absorption after near-total proctocolectomy in dogs: ileal pouch vs. jejunal pouch—distal rectal anastomosis☆☆☆

Bile acid malabsorption is often present in patients after near-total proctocolectomy and ileal pouchanal canal anastomosis, suggesting ileal dysfunction. Experiments were performed in dogs to compare bile acid absorption after a modified procedure, in which a jejunal pouch was interposed between the terminal ileum and the distal rectum, with that after a conventional ileal pouch operation. Fecal bile acid output (equivalent to hepatic bile acid biosynthesis) and composition were determined by gas chromatography/mass spectrometry in five jejunal pouch dogs and in five ileal pouch dogs more than 6 months after operation. Fecal bile acid output in the jejunal pouch dogs (mean +standard deviation) was 215 ±59 mg/day(10.1 ±2.7 mg/kg-day), a value similar to that obtained in the ileal pouch dogs (261 ±46mg/day [12.8 ±3.1 mg/kg-day]; P >0.05). These values were also similar to those reported by others for healthy unoperated dogs, indicating that increased bile acid biosynthesis occurring in response to bile acid malabsorption was not present. Fecal bile acids in pouch dogs were completely deconjugated and extensively 7-dehydroxylated (jejunal pouch = 90.4% ±3.9% dehydroxylated; ileal pouch = 88.6% ±6.6% dehydroxylated) and consisted predominantly of deoxycholic acid derivatives. We conclude that when either a jejunal pouch or an ileal pouch is used as a rectal substitute in dogs, an anaerobic pouch flora develops that efficiently deconjugates and dehydroxylates bile acids, rendering them membrane permeable. The resultant passive absorption of unconjugated bile acids appears to compensate for any loss of active ileal absorption of conjugated bile acids, and bile acid malabsorption does not occur.