DISPACT trial: a randomized controlled trial to compare two different surgical techniques of DIStal PAnCreaTectomy - study rationale and design.

BACKGROUND: Surgery is of increasing importance in the treatment and outcome of diseases of the pancreas worldwide. The incidence of pancreatic cancer (7-11/ 100,000 per year) has risen over the last years and surgical resection remains the only option for definite cure. Twenty-five percent of all resections are left of the superior mesenteric vein (distal pancreatectomy) and the appropriate closure technique for the pancreatic remnant remains unclear. Pancreatic fistulas are the most common (0-40%) and relevant postoperative complication. The optimal surgical strategy for pancreatic resection needs to be identified from the large number of surgical procedures available today. PURPOSE: To evaluate the effectiveness of the two most common surgical techniques for distal pancreatectomy: stapler versus hand-sewn closure of the pancreatic remnant. METHODS: In order to account for the uncertainty and clinical heterogeneity in the management of the pancreatic remnant following distal pancreatectomy, a study protocol is developed on the basis of a retrospective survey of patients in a center of excellence for pancreatic surgery and a systematic review with meta-analysis. RESULTS: The DISPACT trial is a multicentered, randomized, controlled and patient-and observer-blinded trial using a two-group parallel group-sequential superiority design to compare the two techniques mentioned above. It will include approximately 336 randomized patients at up to 20 centers of excellence in pancreatic surgery, who are undergoing elective distal pancreatectomy for resectable benign, malign, and neuroendocrine tumors, chronic pancreatitis and pseudocysts of the pancreatic body and tail. The combination of the rate of postoperative pancreatic fistula and mortality will be evaluated as the primary endpoint. In addition, a set of general and surgical parameters will be analyzed. Pre-specified treatment manuals and continuous intra-operative (photo-documentation of surgical procedures and blinded evaluation thereafter) and on-site monitoring will assure that the treatment of the study patients conforms to protocol and will minimize clinical heterogeneity. Due to uncertainties about the effect sizes of the primary endpoint, an a priori planned interim analysis of the primary endpoint will be conducted after 224 evaluable patients are selected in order to reassess the initially planned sample size. LIMITATIONS: Since pre-existing evidence was limited our initial sample size calculation is based on uncertain assumptions and may need to be modified in a planned interim analysis. Moreover, since surgical experience remains a potential confounder in surgical trials, learning curve bias has to be taken into account when analyzing the results. Given the participating trial sites, standardization of peri-and postoperative treatment represents a major issue of trial conduct. CONCLUSIONS: A group-sequential study design accounts for the uncertainty of pre-existing evidence. Also, standardization of surgical and postoperative care and blinded outcome assessment as well as adjustment for varying surgical expertise will contribute to a high validity and generalizability of the results.

Chronic selenosis in horses fed locally produced alfalfa hay.

Chronic selenosis (alkali disease) was diagnosed in horses of western Iowa, a region associated with marginal to adequate soil selenium. Two locally produced alfalfa hays (Medicago sativa L) were identified as the primary source. Difficulty in selecting diagnostic specimens to evaluate potential chronic selenosis cases is complicated by the wide range of tissue concentrations reported in previous cases, conflicting correlation of sample selenium concentrations in the literature, and different recommendations on specimen selection and diagnostic value. These problems arise form the similarity in clinical signs for mild and severe chronic selenosis cases, and inability to establish the disease time course. Therefore, collection of multiple samples to confirm high selenium concentration in various tissues and identify selenium sources is recommended. Value of samples believed to reflect historical exposure vs current status may be questionable. Interpretation of results by practitioners and diagnosticians should consider selenium exposure level and duration, antagonistic or ameliorating factors, and postexposure excretion.

Characterization of an epizootic of pulmonary edema in swine associated with fumonisin in corn screenings.

In 1989, corn screenings were associated with acute interstitial pulmonary edema, hydrothorax, and death in swine. Attack rate was 5-50%, case fatality rate was 50-90%, and clinical course was 1-2 days. Screenings from farms with pigs affected with pulmonary edema contained 20-330 micrograms fumonisin B1 per gram. Screenings containing 92 micrograms fumonisin B1 per gram fed to weanling pigs caused pulmonary edema and death. Sterilized corn inoculated with Fusarium moniliforme and diluted 1:1 with clean corn contained fumonisin B1 (17 micrograms/g) and caused acute pulmonary edema when fed for 5 days. Survivors developed subacute hepatotoxicosis with individual hepatocellular necrosis, hepatomegalocytosis, and increased numbers of mitotic figures. Similar liver lesions occurred in pigs given fumonisin B1 intravenously at 0.8 mg/kg body weight for 14 days.

Cocklebur toxicosis in cattle associated with the consumption of mature Xanthium strumarium.

Cockleburs (Xanthium spp.) are herbaceous annuals with worldwide distribution. Toxicoses are usually associated with the consumption of the seedlings in the cotyledon stage, which contain a high concentration of the toxic principle, carboxyatractyloside. The seeds are also known to contain the toxin, but it has long been assumed that the spiny capsule would deter their consumption. Six of 70 yearling calves died while being fed round bale hay composed predominantly of foxtail and mature cocklebur plants with burs. Clinical signs ranged from acute death to hyperexcitability, blindness, tense musculature, and spastic gaits with heads held high and ears erect. Some symptomatic calves would stumble, fall to lateral recumbency, convulse, and later recover. Overall, the herd was very uneasy. Prominent gross lesions were ascites and a firm, pale liver with a mottled hemorrhagic pattern on cut surface. The rumen contained numerous intact burs and well-ruminated grass. Histological examination of the liver revealed marked centrolobular degeneration and necrosis with associated hemorrhage and congestion. Brain lesions were present. Plant and tissue samples were analyzed for carboxyatractyloside with various results. Samples of rumen contents, urine, and burs contained 100-200 ppm, 0.1-0.05 ppm, and 0.1 ppm, respectively. Based on the history, clinical signs, pathological lesions, and chemical analyses, cocklebur toxicosis associated with consumption of mature Xanthium strumarium in hay was confirmed.

Abortion and early neonatal death of kids attributed to intrauterine Yersinia pseudotuberculosis infection.

Yersinia pseudotuberculosis was isolated from placenta and abomasal contents of triplet goat kids, two of which were aborted and one of which died shortly after birth. Necropsy findings in the kids were suppurative placentitis and suppurative pneumonia. The public health implications in intrauterine Yersinia infection in goats are discussed.