Mark J. Koruda

Experimental studies on the healing of colonic anastomoses

The leakage of colonic anastomoses is a potentially devastating surgical complication. Several factors, such as bowel preparation prior to surgery, surgical technique, nutritional status, and intervening pathological conditions, have been identified as significantly influencing the healing of colonic anastomoses. Due to the multifactorial nature, it is difficult to investigate the mechanisms of occurrence and prevention of colonic dehiscence in the clinical setting. For this reason, many experimental models have been used to study colonic healing and the pathogenesis of anastomotic failure. This report reviews the use of animal models for the study of colonic anastomotic healing. Special emphasis is devoted to the rationale for selecting animal models, parameters of healing, factors influencing anastomotic healing as well as the clinical potential of dietary and pharmacologic manipulations proposed to improve colonic healing.

Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection

After massive small bowel resection, total parenteral nutrition (TPN) is prescribed to maintain nutritional status. However, TPN reduces the mass of the remaining intestinal mucosa, whereas adaptation to small bowel resection is associated with increased mucosal mass. Short-chain fatty acids (SCFAs) have been shown to stimulate mucosal cell mitotic activity. This study determined whether the addition of SCFAs to TPN following small bowel resection would prevent intestinal mucosal atrophy produced by TPN. Adult rats underwent an 80% small bowel resection and then received either standard TPN or TPN supplemented with SCFAs (sodium acetate, propionate, and butyrate). After 1 wk, jejunal and ileal mucosal weights, deoxyribonucleic acid, ribonucleic acid, and protein contents were measured and compared with the parameters obtained at the time of resection. Animals receiving TPN showed significant loss of jejunal mucosal weight, deoxyribonucleic acid, ribonucleic acid, and protein and ileal mucosal weight and deoxyribonucleic acid after small bowel resection, whereas animals receiving SCFA-supplemented TPN showed no significant change in the jejunal mucosal parameters and a significant increase in ileal mucosal protein. These data demonstrate that SCFA-supplemented TPN reduces the mucosal atrophy associated with TPN after massive bowel resection and thys may facilitate adaptation to small bowel resection.

The Effect of a Pectin-Supplemented Elemental Diet on Intestinal Adaptation to Massive Small Bowel Resection

The effect of a pectin-supplemented elemental diet on intestinal adaptation to massive small bowel resection in the rat was investigated in this study. Sixty adult Sprague-Dawley rats underwent placement of a feeding gastrostomy and swivel apparatus. Control animals (N = 16) were then returned to their cages while the remaining animals underwent an 80% small bowel resection and anastomosis (resected, N = 44). Postoperatively, animals were randomly assigned to receive either a fat- and fiber-free elemental diet (no pectin) or the same diet supplemented with 2% pectin (pectin). After 8 days of full strength diet, samples of jejunum, ileum, and colon were obtained for analysis. The weights per unit length of the ileum and colon were significantly greater in the resected pectin group than either the resected no pectin or pectin control groups. Mucosal parameters (unit weight, DNA, RNA, and protein content) were significantly increased in the jejunum and ileum of both the resected pectin and resected no pectin...

A prospective evaluation of health-related quality of life after ileal pouch anal anastomosis for ulcerative colitis.

A prospective evaluation of health-related quality of life after ileal pouch anal anastomosis for ulcerative colitis

Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose-based bioresorbable membrane: A prospective, randomized, evaluator-blinded multicenter study

INTRODUCTIONPostoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients.METHODSTwelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no antiadhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.RESULTSData were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose.CONCLUSIONSGlycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.

Health-Related Quality of Life After Ileoanal Pull-Through: Evaluation and Assessment of New Health Status Measures

BACKGROUND & AIMS Health-related quality of life (HRQL) after proctocolectomy is a critical parameter for management decisions in patients with chronic pancolitis. The aim of this study was to evaluate the HRQL of patients with ileoanal pull-through and to validate new, easy-to-administer HRQL measures. METHODS The Sickness Impact Profile (SIP), Short Form 36 (SF-36), Rating Form of Inflammatory Bowel Disease (IBD) Patient Concerns (RFIPC), and the time trade-off (TTO) were used to measure HRQL of pull-through patients. The SF-36 and the RFIPC were validated. RESULTS HRQL of patients with ileoanal pull-through was better than that of a national sample of patients with IBD (SIP and RFIPC) and similar to that of a normal population (SF-36). Physical and psychosocial subscales of the SF-36 correlated with the SIP, affirming the construct validity of the SF-36. The RFIPC results correlated with the SIP and SF-36 results, suggesting that it is also a valid health status measure for these patients. TTO results correlated with the physical subscales of the SIP and SF-36, reflecting the impact of physical health on this group. CONCLUSIONS HRQL of patients with ileoanal pull-through is excellent. The SF-36 and RFIPC are valid health status measures that can be used by clinicians and researchers in these patients.

Prospective randomized trial of early initiation and hospital discharge on a liquid diet following elective intestinal surgery

Length of hospital stay after elective intestinal surgery may be related to patient tolerance of a diet. We hypothesized that early initiation and discharge home on a clear liquid diet would decrease the length of hospital stay without increasing morbidity. The aim of this study was to determine if early initiation and discharge on a clear liquid diet decreases the length of hospital stay and is safe. Forty-four patients were randomly assigned to either a standard diet or a clear liquid diet. A standard diet (n = 17) was begun after the passage of flatus or stool, and consisted of clear liquids to a volume of approximately 750 ml, then three solid meals, and discharge thereafter. Patients randomized to a clear liquid diet (n -27) received 30 ml/hr of clear liquids on postoperative day 2, unlimited clear liquids on postoperative day 3, and were dismissed on a clear liquid diet on postoperative day 4. All patients were followed by a daily telephone call and clinic visit. The primary outcome variable was length of hospital stay. The incidence of postoperative intestinal-related sequelae, complications, and readmission rates did not differ between groups. Posl-discharge intestinal symptoms were common in both groups but tended to resolve faster in the patients on a standard diet. The length of hospital stay was decreased in the patients on a clear liquid diet compared to those on a standard diet (6.1 ±1.1 days vs. 4.4 ±0.2 days; P = 0.09), but total hospital costs did not differ. Early initiation and hospital discharge on a clear liquid diet after elective intestinal surgery decreases the length of hospital stay and is safe.

Chronic ethanol intake and burn injury: Evidence for synergistic alteration in gut and immune integrity

OBJECTIVE Chronic ethanol (EtOH) intake and injury are both associated with increased susceptibility to infection in the host. This study examined the immune and gastrointestinal alterations induced by chronic EtOH intake and injury, and compared the effects of enteral and intravenous administration of EtOH. DESIGN Rats received 20% EtOH daily for 14 days by gavage [oral (PO)] or superior vena cava [intravenous (i.v.)] infusion. Mean blood EtOH concentrations at 90 minutes after administration were 95.3 mg/dL (PO) and 94.4 mg/dL (i.v.). An additional group of animals underwent a 30% total body surface area full-thickness burn injury 4 hours after the final dose of EtOH or normal saline on experimental day 14. All animals were killed 4 days after burn injury. MATERIALS AND METHODS Nonadherent splenic lymphocytes were tested for mitogenic responses to the T-cell mitogens concanavalin A (ConA) and phytohemagglutinin (PHA), and the B-cell mitogens lipopolysaccharide (LPS) and pokeweed. Quantitative bacterial cultures of mesenteric lymph nodes and liver were also performed. Alterations of intestinal mucosa were determined by measurement of ileal mucosal weight, DNA, protein, and diamine oxidase content. Circulating plasma endotoxin concentrations were also measured. MEASUREMENTS AND MAIN RESULTS Chronic PO-EtOH intake induced a significant impairment in mitogenic response to T-cell mitogens, with a fourfold reduction in ConA and a twofold reduction in PHA response (p < 0.05 by analysis of variance) and increased bacterial translocation (70% vs. 10%). Chronic EtOH administered by the i.v. route did not reduce mitogenic response to any of the mitogens studied. Histologic examination of ileal segments demonstrated that chronic PO-EtOH administration was associated with significant mucosal disruption and exfoliation. Chronic administration of PO-EtOH prior to burn injury induced a significant impairment in spleen mitogenic response to ConA, PHA, and LPS when compared with all other burn injury groups. Chronic administration of EtOH by the i.v. route prior to burn injury did not alter splenic mitogenesis. In addition, chronic PO-EtOH prior to burn injury increased bacterial translocation rates (80% vs. 33%) and prevented the normal intestinal reparative response to burn injury (demonstrated by a significant reduction in ileal mucosal weight, DNA, and diamine oxidase content). CONCLUSIONS Enteral but not i.v. administration of EtOH induced significant immunologic dysfunction (demonstrated by altered spleen mitogenic response) and gastrointestinal dysfunction (demonstrated by depressed ileal mucosal weight, DNA, and diamine oxidase content, and increased bacterial translocation rates). In addition, the administration of chronic enteral EtOH prior to injury resulted in significant immune suppression and impaired the hosts ability for normal intestinal repair. These results suggest that this EtOH-induced reduction in immunocompetence may be gut-mediated and that the administration of alcohol prior to injury may result in a synergistic alteration of gut and immune integrity.

The impact of femur fracture with associated soft tissue injury on immune function and intestinal permeability

Alterations in intestinal permeability and immune function were investigated in a murine femur fracture (FFx) model. We postulated that soft tissue injury associated with closed FFx (crush injury) would result in greater immunosuppression that open FFx (surgical division). AKR mice were randomized to four groups (Normal, Sham, Open FFx, Closed FFx) and studied at 24 and 96 h post-injury. Immune function was assessed by splenocyte blastogenic response and class-specific immunoglobulin production. Intestinal permeability was assessed by measurement of whole blood fluorometry after gavage administration of fluorescein-dextran (FITC-dextran). Closed FFx is associated with increased splenocyte blastogenesis and increased immunoglobulin production at 24 h post-injury. This immunostimulatory response was associated with altered intestinal permeability early after injury (FITC-dextran: .185 ± .070 Closed FFx vs. .069 ± .011 Normal, p = .06). Immunosuppression was evident at 96 h post-injury in the closed FFx group, documented by significant reductions in splenocyte blastogenesis to all mitogens studied. The Open FFx group did not demonstrate any reduction in splenocyte blastogenesis at 96 h post-injury. These data suggest that the soft tissue injury associated with Closed FFx is associated with significant immunosuppression and altered gastrointestinal permeability, which may adversely affect the host by increasing the relative risk of post-trauma infection.

Fundoplication improves disordered esophageal motility

Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude ≤30 mm Hg and/or peristaltic frequency ≤80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fun-doplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 ± 18.4 months (mean ± SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fun-doplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 ± 30.9 mm Hg to 83.5 ± 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 ± 28.7% to 87.6 ± 16.3%; P< 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively, after fundoplication. In most GERD patients with esophageal dysmotility, fundoplication improves the amplitude and frequency of esophageal peristalsis, suggesting refluxate has an etiologic role in motor dysfunction. These data, along with prior data showing that postoperative dysphagia is not common, imply that surgeons should apply complete fun-doplication liberally in patients with disordered preoperative esophageal motility.