Uri Freund

Treatment of acute colonic pseudo-obstruction with neostigmine

BACKGROUND Colonic pseudo-obstruction is a poorly understood syndrome, described by Ogilvie, and characterized by signs of large-bowel obstruction, without a mechanical cause. An imbalance in the autonomic nerve supply to the colon has been suggested as the pathophysiology. Recently, promising results with pharmacologic manipulation with neostigmine have been described. STUDY DESIGN A prospective study was undertaken with 11 consecutive patients with clinical and radiologic signs of colonic pseudo-obstruction, in one general hospital, over a 1-year period. Patients were treated primarily with 2.5 mg of neostigmine in 100 mL of saline for 1 hour, under cardiac monitoring. Results were assessed by the clinical and radiologic responses. RESULTS Rapid and effective spontaneous decompression of the colon was achieved in 8 patients after a single dose of neostigmine, within a mean of 90 minutes from the beginning of treatment. In another two patients decompression occurred only after a second dose was administered 3 hours after the first dose. In one patient, no changes were observed and colonoscopic decompression was performed. No significant bradycardia was observed in any of the patients. CONCLUSIONS Neostigmine is a simple, safe, and effective therapy for treatment of colonic pseudo-obstruction.

Perforation of the terminal ileum induced by blast injury: delayed diagnosis or delayed perforation?

Blast injuries are rare, and although blast-induced perforations of the bowel have been described in the past, the entity of a delayed perforation caused by an evolving injury has not been reported. We report three men injured by the explosion of a terrorist bombing in open air. They suffered primary blast injuries, which resulted in isolated perforations of the terminal ileum. They were operated at different times after the blast event. The resected specimens were examined under light microscopy. One patient was operated immediately, and had three perforations in the terminal ileum. In the other two patients, abdominal complaints appeared only 24 and 48 hours later. These two patients were found to have hematomas in the wall of the terminal ileum, and small perforations therein, with almost no contamination of the peritoneal cavity. On histological examination, there were small perforations with disruption of all intestinal layers. In the vicinity of the perforations, the mucosa was necrotic and disorganized. The submucosa showed edema and vascular thrombi, and at several points mucus was shown dissecting through the muscularis propria, thus creating minute microperforations. Because of the findings in these patients, we suggest a mechanism of evolving damage to the bowel wall and delayed perforation rather than delayed diagnosis, after blast injuries. We suggest that patients exposed to a significant blast should be watched carefully for at least 48 hours.

Octreotide Treatment in Patients with Severe Acute Pancreatitis

We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case–control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. Since January 1992, we have been conducting a prospective randomized study on the effect of octreotide in severe acute pancreatitis, in three hospitals in Israel. The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). The end points of the study included: complication rate (ARDS, sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. From January 1992 to December 1996, 60 patients entered the study. After evaluating the files, 10 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis (24% vs 76%, P = 0.0002) and ARDS (28% vs 56%, P = 0.04). The hospital stay was shorter in the treatment group (20.6 vs 33.1 days, P = 0.04). Two patients died in the treatment group and eight in the control group (P < 0.019). These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis.

Enema-induced perforation of the rectum in chronically constipated patients

INTRODUCTION: The use of retrograde irrigation enemas is common in the treatment of chronic constipation, especially in the elderly. Perforation of the rectum and sigmoid colon caused by cleansing enemas, used by chronically constipated patients, has not been previously described. METHODS: We reviewed all patients with colorectal perforations caused by irrigation enemas admitted to our service in the three-year period between January 1995 and December 1997. RESULTS: Thirteen patients were treated by our surgical service because of perforations of the rectum and sigmoid colon related to a previous retrograde irrigation enema. Ten of these patients came from nursing homes, and the other three lived at home. The relevant information relating the enema administration to the patients condition was given in only two of the ten patients referred to the emergency room by the institutions nursing or medical staff. In the other eight the information was vague and sometimes misleading. The diagnosis of colorectal performation was made by history, plain abdominal x-rays, and CT scan with or without meglumine diatrizoate enemas. Ten patients survived, regardless of age, previous diseases, or operative findings. In all of them, diagnosis was made within 36 hours from the perforation. The three deaths occurred in patients in whom the diagnosis was made late. CONCLUSIONS: Awareness of the possible injury from enemas administered to chronically constipated patients should be stressed. A high degree of suspicion by the attending physician is extremely important, because prompt diagnosis and early surgical treatment carries a relatively good prognosis.

Experimental Acute Necrotising Pancreatitis: Evaluation and Characterisation of a Model of Intraparenchymal Injection of Sodium Taurocholate in Rats

OBJECTIVES To evaluate a simple model that produces progressive dose dependent pancreatitis, by intraparenchymal injection of sodium taurocholate. DESIGN Open laboratory study. SETTING Teaching hospital, Israel. MATERIALS Forty eight Wistar rats. INTERVENTIONS Sodium taurocholate was injected, 0.3 ml/100 g body weight, in concentrations of 5% and 10% into the pancreatic parenchyma of 32 Wistar rats, resulting in two distinct groups of severity. In 16 sham controls, saline was injected into the pancreas in similar fashion. Blood samples were withdrawn before, and 6, 24, 48, and 72 hours after induction of pancreatitis. RESULTS Six hours after taurocholate injection, there was a sharp increase in the plasma activities of amylase, lipase, and lactate dehydrogenase (LDH). After 24 hours plasma activities of amylase and lipase decreased to near normal values while LDH remained slightly increased for 48 hours and decreased only after 72 hours. At 6 hours after the injection, interleukin-6 (IL-6) concentrations had increased slightly in the 5% group and decreased to the baseline values at 24 hours. In the 10% group, the increase in IL-6 values was significantly greater than in the 5% group (p = 0.04), and correlated well with severity of pancreatitis as defined by histology (p = 0.01) and mortality (p = 0.037). Twenty four hours after injection of taurocholate, morphological changes comprising diffuse necrosis of the pancreas, fat necrosis, and intestinal dilatation secondary to paralytic ileus were severe. Histopathological examination of the pancreas showed good correlation with the clinical findings and with mortality. No morphological changes were detected when saline was injected into the pancreas (sham control), and only mild rises of IL-6, lipase, amylase, and LDH activities were seen at 6 hours after injection. The mortality, after 10 days, was 80% in the 10% taurocholate group, 30% in the 5% taurocholate group, and 0 in the sham control group (p < 0.05). CONCLUSION The intraparenchymal injection of taurocholate is easy to perform and highly reproducible. The histopathological injury is dose-dependent, as is the mortality. We conclude that this model is valuable for the study of new treatments for pancreatitis.

Successful High-Dose Calcium Treatment of Aluminum-Induced Metabolic Bone Disease in Long-Term Home Parenteral Nutrition

A patient who developed severe metabolic bone disease is presented. He had received long-term home parenteral nutrition (HPN) following extensive small bowel resection after mesenteric vein thrombosis. Bone disease caused by aluminum intoxication had components of osteomalacia and low-turnover osteoporosis. Aluminum was detected at the surface of mineralized bone and was elevated in the serum, resulting in a positive deferoxamine infusion test. One year of treatment with high doses of calcium (up to 24 mEq per day) significantly diminished the patients bone pain, increased the serum levels of calcium, abolished aluminum deposits in the mineralized trabecula, improved bone formation, and increased trabecular bone volume as assessed by repeated histomorphometric analysis.

Evaluation of inflammatory cytokines as prognostic markers in experimental acute pancreatitis in rats

Background: Early evaluation of the severity of acute pancreatitis requires measurements of many variables. Clinical parameters as well as CT scan have traditionally been used as predictors of severity, and complications. None of them however can predict the outcome early and reliably. Inflammatory cytokines were shown to play an important role in the inflammatory cascade, which occurs early in the course of the disease. The aim of the present study is to evaluate the predictive value of plasma interleukin-6 (IL-6) and interleukin-1 (IL-1) levels in experimental pancreatitis in rats. Methods: Male wistar rats were anesthetized and pancreatitis was induced by intraparenchymal injection of 5% (group 2) and 10% (group 3) sodium taurocholate (TC), resulting in 2 distinct groups of severity. In sham controls (group 1), saline was injected into the pancreas in the same fashion. Blood samples were obtained before and 2, 4, 24, and 96 hours after the induction of pancreatitis and plasma amylase, lipase, LDH, IL-1 and IL-6 levels were measured. Mortality was recorded every 8 hours. Pancreatitis severity was also assessed by histopathology. Results: Four hours after pancreatitis induction, plasma amylase, lipase and LDH levels were markedly increased in the pancreatitis groups. In the sham control group, moderate increases were also observed. No consistent significant difference in amylase, lipase or LDH levels was observed between the groups. At 2 hours from pancreatitis induction, IL-6 levels increased mildly in-groups 1 and 2, and decreased to the baseline levels at 24 hours. In-group 3, the increase in IL-6 levels was significantly higher then in-groups 1 and 2 (p=0.029 and 0.036 respectively), and correlated well with pancreatitis severity as defined by pathology (p=0.01) and mortality rates (p=0.037). No difference in IL-1 levels was observed at 2,4 and 24 hours from induction. At 96 hours IL-1 levels were higher in group 3 then in groups 1 and 2 (p=0.037). Conclusion: IL-6 plasma levels correlated well with the severity of the disease as reflected by the mortality rates and pathological score. IL-6 levels may be a reliable predictor of severity and mortality in acute pancreatitis. This marker can be used as early as 2 hours and up to 24 hours from the beginning of the inflammatory process. IL-1 levels at 96 hours also correlated with pathology, but were not found to predict outcome at the early phases of the disease.

THE EFFECT OF THE SOMATOSTATIN ANALOGUE OCTREOTIDE ON EXPERIMENTAL INTESTINAL OBSTRUCTION IN RATS

Background: Somatostatin has an inhibitory effect on the endocrine and exocrine secretions of the gut. It may have a beneficial effect in the conservative treatment of intestinal obstruction. The aim of the present study is to investigate the effect of octreotide in mechanical intestinal obstruction in rats. Method: Intestinal obstruction was induced in rats by ligation of a segment of the distal ileum. Animals were treated with the somatostatin analogue octreotide (n=16), or saline (n=16). Eight rats were operated but their intestine was not ligated (n=8) serving as sham controls. Forty eight hours after the operation, the animals were operated upon again and blood samples from the femoral vein were tested for electrolytes, urea, glucose, lactic acid, amylase, ph and bicarbonate. Portal vein blood samples were also obtained and tested for lactic acid and amylase. Results: Intestinal obstruction resulted, after 48 hours, in severe dilatation of bowel loops. A significant increase in plasma levels of urea, amylase and lactic acid was observed. Plasma pH decreased. In blood samples from the portal vein, a significant increase in lactic acid was observed, indicating metabolic acidosis, probably secondary to bowel ischemia. Octreotide treatment, resulted in less acidosis, with concomitant lower urea and lactic acid levels in the plasma and especially in the portal vein. Conclusion: Octreotide treatment may have a beneficial effect in the conservative treatment of selected cases of intestinal obstruction.

Ileocolic intussusception in an adult

Two weeks after appendectomy a right hemicolectomy was performed on a 35-year-old man because of an ileocolic intussusception. The appendiceal stump was the leading point of the intussusception. Ileocolic intussusception is a very rare complication after appendectomy. The clinical symptoms, diagnostic features, and mode of treatment are discussed.