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Beneficial effects of cyclosporine and rapamycin in small bowel ischemic injury.

Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A and rapamycin, both potent novel immunosuppressants which act on signal transduction pathways in CD4+ T-cells, could potentially modulate immune/inflammatory cellular reactions involved in tissue ischemia/reperfusion injury. We hypothesized that cyclosporine A and rapamycin would preserve mucosal cell function and attenuate inflammatory T-cell-mediated cellular changes associated with small bowel ischemic injury. Forty Sprague-Dawley rats underwent 60 min of gut ischemia by vascular occlusion of the superior mesenteric vessels. Animals were randomized to four groups (n = 10): cyclosporine A (CSA, 5 mg/kg/day SQ), rapamycin (RAP, 2 mg/kg/day SQ), cyclosporine A and rapamycin (C&R), and vehicle given to controls (CON). Following 1 hr of reperfusion, small bowel was harvested for xanthine oxidase (XO, units/mg protein) and maltase (MALT, mM substrate degraded/min/g protein) assays. Blood was obtained from the portal vein for tumor necrosis factor-alpha (TNF-alpha, pg/ml) assay. The results of the study are presented below (mean +/- SEM, *, P < 0.05 versus controls). (Table in text) The results indicate that cyclosporine and rapamycin each play a significant role in attenuating ischemia/reperfusion injury in the gut. These data suggest that there are cytoprotective and anti-inflammatory mechanisms of these drugs independent of T-cell signal transduction that provide some protective effect in small bowel ischemia. Furthermore, T-cell-mediated immune mechanisms may not be associated with the adverse effects of small bowel ischemia/reperfusion injury. Additional investigation will be necessary in order to define the role of T-cell-mediated immune injury in the gut and how this relates to the beneficial effect of immunosuppression in small bowel mucosal ischemic injury.

Animals↗

Controlled trial of laparoscopic-assisted vs open colon resection in a porcine model.

BACKGROUND: Several series of laparoscopic colon resection have been reported in the literature with varied results; however, no controlled series of laparoscopic vs open colon resection has been reported. The purpose of this study was to determine the relative safety and adequacy of laparoscopic colon resection in a controlled trial using a porcine model. METHODS: Domestic pigs (n = 23) were randomly divided into two groups. Animals underwent either an open or laparoscopic-assisted segmental resection of the sigmoid colon. The open resections were performed through a 20-cm midline incision and the laparoscopic technique utilized five 12-mm ports. Laparoscopic resection took twice as long to complete as open resection (P < 0.001). Return of gastric function was significantly faster in the laparoscopic group than in the open group (P < 0.032). RESULTS: No significant differences were found in total length of resection, proximal or distal margins, number of lymph nodes recovered, length of mesenteric vessel resected, or time to return of bowel function. At vivisection, more adhesions to the abdominal wall were noted in the open group (P < 0.002). One death occurred in the laparoscopic group 2 h postoperatively (8.3% mortality) while all open group pigs survived. However, there was no statistically significant difference in mortality rates by chi-square analysis (P > 0.5). CONCLUSIONS: Despite longer operative time, laparoscopic intervention is technically feasible, safe, and may offer significant postoperative benefits due to fewer abdominal adhesions.

Anastomosis, Surgical↗

[Congenital duodenal stenosis in adulthood].

A high-grade duodenal stenosis in adults can, in rare cases, be congenital, and its cause is found in an intraduodenally sited membrane. The anamnesis reveals growth disorders with vomiting and meteorism and abdominal complaints. A perforation opening in this membrane is the reason for survival into adulthood. The X-ray appearance and deep duodenoscopy make the diagnosis easy. Volvulus in cases of malrotation, Ladd's ligaments, annular pancreas, and compression of the duodenum by mesenteric vessels must be considered in the differential diagnosis. When the intraduodenal membrane is resected it is most important to expose the papilla Vateri, since this not uncommonly ends in the area of the septum. If necessary, a duodenoduodenostomy is performed. If the windsock web abnormality is present the duodenum should be opened at the point of attachment of the diaphragm. The construction of a gastrojejunostomy should be avoided.

Adult↗

Midgut volvulus as a complication of intestinal malrotation in adults.

Seven adults with midgut volvulus as a complication of malrotation are presented. All patients were men with an average age of 33 years. Four presented with long histories of intermittent abdominal pain. In three patients, the twisted, corkscrew appearance of the barium column in the duodenum and proximal jejunum in an upper gastrointestinal series made the diagnosis. In the remaining patient, small-bowel follow-through performed three years before surgery showed intestinal malrotation. Three patients presented with the acute onset of severe abdominal pain. Plain films showed small-bowel obstruction and pneumatosis intestinalis in two patients and only nearly complete small-bowel obstruction in the third. Barium studies were not done in this group because of the need to proceed to exploratory laparotomy and the risk of perforation. In one patient, abdominal angiography suggested the diagnosis by showing abnormal courses of the mesenteric vessels to the volvulized segment of small bowel. All three of these patients showed ischemic segments of bowel at laparotomy.

Abdomen, Acute↗

Uncommon features of polyarteritis nodosa: psychosis and angio-oedema.

Psychosis and swelling of the face and hands are rarely observed in adult polyarteritis nodosa (PAN). We describe a 21-year-old woman who presented with fever, livedo reticularis, tender subcutaneous nodules and arthritis. These manifestations did not respond to prednisone, but remitted when the drug was tapered. She had had psychosis since the age of 16 years. During the flares of the disease she presented with facial, periorbital and hand swelling. This finding is rarely observed in adult PAN. Arteriography showed multiple small aneurysms, of the mesenteric vessels consistent with a diagnosis of PAN. Our report discusses the diagnosis of PAN and emphasises the uncommon presentation of this case.

Adult↗

Surgical treatment of mid-gut carcinoid tumors.

Coincident with medical antitumor treatment of 138 patients suffering from mid-gut carcinoid tumors, 51 patients were subjected to surgery with the principal aims of removing primary tumors and debulking mesenteric or liver metastases. Sixteen patients had previously been operated with intestinal resection or, when the tumors had been considered inexcisable, with intestinal bypass or laparotomy alone. Apart from exhibiting symptoms related to the carcinoid syndrome, the majority (approximately 60%) of the 51 patients had generally intermittent, subileus-like abdominal pain and weight loss. In 18 patients, these symptoms were pronounced and associated with intestinal obstruction or severe malnutrition. Computed tomography and arteriography efficiently demonstrated mesenteric and liver metastases. At laparotomy, the primary intestinal tumors were small, mainly less than 1 cm in diameter, and they were multiple in 39% of the patients. Mesenteric metastases measuring up to 12 cm in diameter were present in 86% of the patients. These metastases were frequently associated with a pronounced mesenteric and retroperitoneal fibrosis causing fixation, angulation, and obstruction of the bowel as well as incipient intestinal gangrene in 8 patients. In all but 6 patients, the primary tumors could be removed by comparatively limited intestinal resections although bulky mesenteric metastases were often dissected from the mesenteric vessels. Liver metastases, found in 49% of the patients, were generally bilateral and multiple, and major hepatic metastases were resected in 6 patients. The results support a role for surgery also in the more compromised patients with mid-gut carcinoid tumors and that such intervention may be associated with considerable symptomatic relief and substantial periods of survival.

Adult↗

[Nonocclusive ischemic enteropathy--a rare cause of ileus].

The cause for a nonocclusive ischemic enteropathy seems to be a low cardiac output syndrome. There are often signs of a paralytic intestinal obstruction. Parameters of the blood chemistry offer no conclusive data. The angiogram of the mesenteric vessels demonstrates extensive arterial vasoconstriction as well as an obstructed venous outflow. Experimental findings disclose that this venous obstruction may be a result of an ischemic contracture in the course of a low flow state. This rigor initiates finally a thrombosis of the venoles. The rigor can be effectually mastered by energy-rich compounds.

Calcium↗

Liver metabolic effects of intestinal shock and naloxone treatment in the rat.

The liver metabolic response of rats following a standardized intestinal shock, induced by applying a pressure of 120 cm water on the mesenteric vessels for 60 min, was studied. Immediately prior to the release of the pressure on the vessels saline or naloxone was given either as a single injection or as a continuous infusion. After the reperfusion of the intestine no early disturbances in liver metabolism were found as evidenced from the ATP, glucose and lactate levels in liver biopsies taken 15 min following reflow. Within 60 min of reflow reduction of ATP and increases of glucose and lactate levels occurred. There were no major hemodynamic or liver metabolic differences between saline- and naloxone-treated shocked rats. When saline or naloxone was given as a continuous infusion, the changes in liver metabolism were, however, less severe than those observed in the single injection situation pointing toward a non-specific effect of volume replacement rather than a blockade of opioid receptors. Hepatic hypoxia and/or cellular effects of "shock factors" could be mechanisms of pathophysiologic importance for the disturbed liver metabolism in this shock model.

Acid-Base Equilibrium↗

Sonographic diagnosis of obstructed afferent loop.

We reviewed the sonographic findings in four patients with afferent loop obstruction from tumor of the gastric stump. All had undergone partial gastrectomy with Billroth type II gastrojejunostomy. The obstructed afferent loop was visible in all cases as a distended fluid-filled segment with multi-layered wall and few mucosal folds. Its course could be traced from the region of the hepatic hilum to the gastric stump. In two patients, the relationships between the loop and the mesenteric vessels, aorta and inferior vena cava allowed us to recognize it as postoperative duodenum. Thickening of the gastric remnant and obstructive jaundice were diagnosed in three cases. Since sonography is often used as the first imaging method in patients with abdominal complaints, knowledge about postsurgical appearance of the gastrointestinal tract is very important in detecting such pathological conditions.

Afferent Loop Syndrome↗

Correlation between serum dopamine-beta-hydroxylase activity and dopamine-beta-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands.

Serum dopamine-beta-hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine-beta-hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14-16 weeks of age, a negative correlation with dopamine-beta-hydroxylase activity in locus coeruleus at 3 weeks and 14-16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14-16 weeks of age.

Adrenal Glands↗

Detection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer.

PURPOSE: This study was designed to select the best monoclonal antibody to stain malignant cells in peritoneal wash fluid, and to investigate the incidence of free malignant cells in preresection and postresection colorectal cancer peritoneal washings using a combination of conventional cytology and immunocytochemistry. METHODS: Peritoneal washings were taken from 35 consecutive patients undergoing colorectal cancer resection. RESULTS: Malignant cells were isolated on a density gradient and identified by conventional cytology and an indirect immunoperoxidase stain. Malignant cells were identified in peritoneal washings from 15 patients (preresection only n = 3, postresection only n = 4, both n = 8). The origin of free malignant peritoneal cells in 11 preresection-positive washings must be the serosa. The origin of these cells in the four postresection-positive patients is uncertain: serosal and luminal spillage were considered unlikely and no circulating cells were found in the mesenteric vessels near the tumor. CONCLUSION: Tumor cells may have leaked out from lymphatics cut during the dissection.

Aged↗

Fulminant second-set allograft rejection and endoscopic findings following small bowel transplantation in the rat.

In the presensitized recipient who has been exposed to donor antigens, second-set rejection takes the form of severe hyperacute graft rejection. Second-set allograft rejection was studied following small bowel transplantation in the rat. Heterotopic intestinal grafting was performed from DA (RT1a) donors to PVG (RT1c) recipients 4 weeks after DA skin sensitization. The endoscopic images and histological specimens were compared with those of syngeneic and first-set rejected grafts. Endoscopically, diffuse erosions of the graft were detected from day 1. Mucosal necrosis progressed rapidly, and was accompanied by massive bleeding on days 3-5. These findings were similar to the course of severe necrotizing hemorrhagic enteritis. Histologically, interstitial edema and hemorrhage with massive infiltrations of neutrophils were manifested from day 1. Mesenteric vessels were completely occluded by thrombi on days 3-5. The grafted intestine had became totally necrotic by day 5. Microscopic findings strongly suggested that destructive graft necrosis was due to vascular damage caused by humoral factors. All the presensitized rats (n = 11) died showing systemic septic signs by day 11 after small bowel transplantation. We conclude that lethal hyperacute rejection occurred in presensitized recipients, even when the graft was transplanted heterotopically. Endoscopic evaluation is beneficial for the early diagnosis of graft rejection. Immediate graft removal should be mandatory as a rescue treatment in second-set rejection of the small intestine.

Animals↗

Carcinoid tumors, vascular elastosis, and ischemic disease of the small intestine.

Ischemic enteritis or infarction occurred in four of 15 patients who had carcinoid tumors of the small intestine. All four, in addition, had elastic vascular sclerosis of the mesenteric vessels. Both arteries and veins were involved, and the change occurred in the region of tumor deposit. In none of the cases was the tumor occluding the lumen of the vessels, nor was there any evidence of thrombosis. Similar elastosis is seen in cancers of the colon, stomach, and breast, and occurs also with thermal injury and irradiation. The findings of the present study would suggest a direct rather than a humoral effect. It would appear that cancer cells exert an inductive effect on the fibroblast or smooth-muscle cell in vascular walls, with excess production of elastic tissue.

Adult↗

Functional, histological, and inflammatory changes in chronically rejecting small bowel transplants.

Our aim was to develop a model of chronic rejection (CR) in small bowel allografts, and to study the changes occurring in these grafts. Small bowel transplantation was performed using the DA to AS rat strain combination. Short-term (5 mg/kg intramuscular, from days -2 to +9), or long-term cyclosporin treatment (5 mg/kg, 3 times a week until day 50) was given to prevent acute rejection. Controls were untreated allografts, DA isografts with and without cyclosporin, and normal DA and AS rats. They were followed for 50 and 100 days after transplantation. Recipients of a syngeneic graft lost weight during the first week after transplantation, but started to regain weight and kept growing thereafter. Histology showed normal bowel architecture with normal mesenteric lymph nodes and Peyers patches. Vigorous acute rejection occurred in the untreated allografts. Animals had persistent weight loss, and were killed between 6-13 days after transplantation. No clinical signs of graft-versus-host disease were seen. Histology showed end-stage acute rejection. In both cyclosporin-treated allografted groups the postoperative course was as in the isografted animals. However, all animals had histologic signs of CR by 50 and 100 days after transplantation. Changes were most prominent in the mesentery. Serositis with increased vascularity, inflammation with sclerosis, and patchy myointimal proliferation with endothelialitis of the mesenteric vessels were found. Changes in the bowel were patchy and included some thickening of the muscle coat, crypt hyperplasia, scattered necrotic cells in the crypts, slight blunting of villi and loss of goblet cells. Infiltrating cells in the mesentery and bowel consisted mainly of CD 4+ cells, CD 8- T-cells and monocytes/macrophages. Lactulose-mannitol urinary excretion ratio was significantly increased in short-term cyclosporin treated allografts at days 50 and 100 posttransplant. Serum albumin levels were significantly lowered in this group at both time points examined. We developed two models in which CR occurs after small bowel transplantation. Long-term cyclosporin treatment delayed the development of CR, since functional abnormalities were only seen in the animals that were treated with short-term cyclosporin.

Animals↗

Retroanastomotic hernia after gastrojejunostomy: US and CT findings with an emphasis on the whirl sign.

BACKGROUND: We reviewed ultrasound (US) and computed tomographic (CT) findings of retroanastomotic hernia and established whether such findings are characteristic of retroanastomotic hernia in patients who have undergone gastrojejunostomy. METHODS: During a recent 10-year period, we encountered 13 consecutive cases of retroanastomotic hernia. Of the patients involved, 11 underwent US, 10 underwent CT, and three underwent small bowel followthrough imaging. The US and CT scans were retrospectively reviewed to determine abnormal findings. Surgical proof was available in all cases. RESULTS: The efferent loop was herniated through the defect created behind the anastomosis in 10 cases, the efferent and afferent loops in two cases, and the afferent loop in one case. Retroanastomotic hernia was prospectively suggested in 12 of these 13 cases. Among the 10 cases of efferent loop herniation, US and CT signs of retroanastomotic hernia included whirling of mesenteric vessels, jejunal loops, and mesentery in the periumbilical abdomen (10 of 10); mural thickening of herniated bowel loops (six of 10); dilatation of herniated bowel loops (four of 10); decreased peristalsis of herniated bowel loops on US (three of nine); and decreased contrast enhancement of herniated bowel loops on CT (one of seven). In one case, US and CT signs of retroanastomotic hernia of the afferent loop included its dilatation and whirling of a short length of afferent loop behind the anastomosis. In two cases, US and CT signs of retroanastomotic hernia of the afferent and efferent loops included findings of afferent and efferent loop herniations. Three of 13 cases had reversible bowel ischemia, and one had bowel necrosis. CONCLUSION: Retroanastomotic hernia is an important condition, and the US and CT findings we have described might suggest its diagnosis.

Adult↗

Mesenteric panniculitis: sonographic findings.

BACKGROUND: Mesenteric panniculitis (MP) is a relatively rare disease, and sonographic (US) and color Doppler findings have been infrequently reported. METHODS: We reviewed the clinical data and US and Doppler results of three cases of MP to determine the role and limitations of these techniques. RESULTS: The sole presenting clinical sign was a soft mass. On US the lesion was imaged as a poorly margined echogenic mass with hypoechoic areas. Color Doppler US visualized the nondeviated mesenteric vessels within the mass, which enabled us to perform a safe guided biopsy. CONCLUSIONS: US is useful as an initial diagnostic tool, but its results must be interpreted carefully. Color Doppler US is very useful in demonstrating fine vessels and helps in performing a safe needle biopsy.

Humans↗

Hemorrhage after duodenopancreatectomy: impact of neoadjuvant radiochemotherapy and experience with sentinel bleeding.

Postoperative hemorrhage (PH) after duodenopancreatectomy (DP) is frequently lethal. The aim of this study was to delineate guidelines of management. Between August 1994 and July 2003, 172 patients underwent DP for cancer. Altogether, 26 patients were subjected to an institutional protocol (IP) with standard-dose chemoradiation (CRT) and 4 patients to an extrainstitutional protocol (EIP) with high-dose CRT. Sixteen patients (9.3%) were reoperated for PH. Hemorrhage occurred in 23% of irradiated patients (4 EIP, 3 IP) and in 6% of nonirradiated patients [confidence interval (CI) 1.8-6.5]. Pancreatic leak occurred in nine patients with PH (56%). Sentinel bleeding (SB) was noted in eight patients (50%) with a mean delay of 10 days after DP. Overall mortality after hemorrhage was 56%. Morality rates of patients with EIP or IP were, respectively, 100% and 0%. Mortality rates of patients with or without SB were similar. Mortality rates of axial bleeding (hepatic artery, mesenteric vessels) or lateral bleeding (pancreas remnant, splenic vessels) were, respectively, 88% and 25% (CI 1.6-8.6). Completion of pancreatectomy was achieved in 75% without rebleeding. Preoperative high-dose CRT increased the risk of fatal PH. Because SB occurs before massive hemorrhage, prompt reoperation could reduce mortality. Completion of pancreatectomy was essential during reintervention. Axial bleeding supports high mortality. Moving to the left, the pancreatojejunostomy could avoid contact of pancreatic juice with axial vessels in the case of pancreatic leakage. Ligating the gastroduodenal artery during DP had to leave a stump of around 1 cm to facilitate hemorrhage control without ligating the common hepatic artery.

Adenocarcinoma↗

Acute appendicitis in a young adult with midgut malrotation: a case report.

Midgut malrotation is defined as a developmental anomaly that may cause atypical clinical symptoms in relatively common intestinal disorders due to altered anatomy. A 27-year-old woman presented with acute left-sided abdominal pain. Underlying type Ia malrotation prevented the correct clinical diagnosis of perforated, ulcerated appendicitis. Cross-sectional imaging demonstrated all the typical signs of this type of malrotation, i.e., right-sided duodenojejunal junction, left positioned cecum and ascending colon, inverted position of the superior mesenteric vessels, and hypoplasia of the uncinate process of pancreas, and surgical treatment was initiated.

Abdominal Pain↗