Necrosectomy and postoperative local lavage in patients with necrotizing pancreatitis: Results of a prospective clinical trial

Seventy-four patients with necrotizing pancreatitis were included in a prospective clinical trial of a surgical management protocol comprising necrosectomy and postoperative local lavage of the lesser sac and of the necrosis cavity. Fifty-eight patients showed preoperative organ failures such as pulmonary dysfunctions (57%), renal dysfunctions (37%), shock (12%), and sepsis (26%) in spite of intensive care treatment. The median value of the early prognostic signs was 4.5 points. Intraoperatively, 62% of the patients revealed extensive intrapancreatic parenchymal necrosis, 69% had extrapancreatic necrosis, and 39% showed bacterial contamination of the necrotic material. Following the necrosectomy, postoperative local lavage was performed for an average period of 25 days with 7 liters (median) of lavage fluid per 24 hours. In each of 18 studied patients, a considerable release of immunoreactive trypsin was demonstrated and, in each of 20 studied patients, a high concentration of immunoreactive phospholipase A₂ was demonstrated in the lavage fluid up to the 12th/14th postoperative day. The intensive care period averaged 6 1/2 days, the hospital stay averaged 54 days. The hospital mortality rate was 8.1%. It is concluded that restricted necrosectomy and postoperative local lavage treatment correspond in particular to the pathomorphologic conditions and to the local release of biologically active compounds such as bacteria, endotoxin, trypsin, and phospholipase A₂ in patients with necrotizing pancreatitis.

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Resumen Setenta y cuatro pacientes con pancreatitis necrotizante fueron incluídos en un ensayo clínico prospectivo aplicando un protocolo de manejo quirÚrgico que comprende necrosectomía y lavado peritoneal postoperatorio de la transcavidad de los epiplones y de la cavidad necrótica. Cincuenta y ocho pacientes exhibierion fallas orgánicas postoperatorias tales como disfunción pulmonar (57%), disfunción renal (37%), shock (12%), y sepsis (26%) a pesar de cuidado intensivo. El valor promedio de los signos précoces pronóstico (Ranson), con exclusión de la retención de líquido fue de 4.5 puntos. Los hallazgos intraoperatorios revelaron necrosis pancreática extensa en 62% de los pacientes, necrosis extrapancreática en 69%, y contaminación bacteriana del material necrótico en 39%. Realizada la necrosectomía se instauró lavado peritoneal postoperatorio por un período promedio de 25 días con 7 litros (promedio) de líquido por cada 24 horas. En cada uno de los 18 pacientes estudiados se demostró liberación considerable de tripsina inmunorreactiva, así como una elevada concentración de fosfolipasa A₂ inmunorreactiva, en el líquido de lavado hasta el 12/14 días postoperatorios. El período de cuidado intensivo fue de 6 1/2 días, y la hospitalización de 54 días en promedio. La mortalidad hospitalaria fue de 8.1%. En conclusión, se plantea que el tratamiento mediante la necrosectomía restringida y el lavado peritoneal local postoperatorio está indicado en pacientes con las condiciones patomorfológicas de pancreatitis necrotizante que resultan en la liberación local de compuestos biológicamente activos tales como bacterias, endotoxina, tripsina, y fosfolipasa A₂. Serán necesarios ulteriores estudios clínicos controlados para confirmar los resultados favorables que hemos obtenido con la necrosectomía y el lavado peritoneal postoperatorio en pacientes con pancreatitis necrotizante y extensa e infectada necrosis pancreática.

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Résumé Un essai prospectif d'une méthode de traitement chirurgical consistant en nécrosectomie associée au lavage de l'arrière cavité des épiploons et de la cavité nécrotique a concerné 74 malades présentant une pancréatite nécrotique. Malgrè le traitement intensif 58 d'entre eux ont accusé des complications telles que troubles pulmonaires (57%), rénaux (37%), choc (12%), et infection (26%). La valeur moyenne des signes de pronostic précoce fut de 4.5 points. A l'intervention 62% des opérés présentaient une nécrose pancréatique étendue, 69% des opérés une nécrose extra-pancréatique, 39% une surinfection du tissu pancréatique. Après l'exèrése de la nécrose le lavage fut pratiqué quotidiennement avec en moyenne 7 litres de liquide pendant une période de 25 jours. Chez 18 malades fut constaté une libération importante de trypsine immunoactive et chez 20 malades un taux élevé de phospholipase cA dans le liquide de lavage pendant 12/14 jours après l'intervention. La durée des soins intensifs fut en moyenne de 6.5 jours et celle de l'hospitalisation de 54 jours. Le taux de mortalité opératoire fut de 8.1%. On peut conclure de ces faits que la nécrosectomie limitée, associée au lavage local constitue un traitement adapté aux lésions et à la libération locale d'éléments biologiques pathologiques: bactérie, endotoxine, trypsine, et phospholipase A au cours de la pancréatite nécrotique.

     

The role of phospholipase A2 in human acute pancreatitis

Summary Several studies suggest that the activation of pancreatic phospholipase A₂ (PLA₂) and its release from injured acinar cells play an important role in the pathogenesis of acute pancreatitis. Elevated catalytic activity of PLA₂ in serum is associated especially with severe forms of the disease. PLA₂ has been purified from human cadaver pancreas and an antiserum raised against the enzyme in rabbits. Immuno-histochemical localization of PLA₂ in pancreatic tissue was abnormal in acute pancreatitis. A time-resolved fluoroimmunoassay for human pancreatic PLA₂ has been developed. Increased serum concentrations of immunoreactive PLA₂ were found in acute pancreatitis during the first week after hospital admission. The values returned to normal somewhat more slowly than corresponding serum amylase values. The immunochemical determination of PLA₂ in serum provides a fast and specific detection of injury to pancreatic acinar cells. The pancreas is not the only source of PLA₂ in acute pancreatitis. The nonpancreatic PLA₂ may originate from various inflammatory cells, but this hypothesis remains to be proven.     

Fixation of femoral shaft osteotomy with an intramedullary composite rod: an experimental study on dogs with a two-year follow-up

A novel composite material with an ultra-high strength and a low elastic modulus called carbon fibre-reinforced liquid crystalline polymer (LCP/CF) has been developed. An experimental diaphyseal osteotomy of the proximal femur in fourteen Beagle dogs was fixed with an intramedullary LCP/CF rod of 4.5 mm in diameter and 80 mm in length. The radiological follow-up intervals were 1, 3, 6, 12, 24, 52, and 104 weeks. Five dogs were killed at 1 year and three dogs at 2 years for histological studies; six dogs were retained for longer follow-up. Radiographs showed an uncomplicated healing of the diaphyseal osteotomy with an external callus formation in all dogs in 12 weeks. Histological analysis revealed a benign host tissue response with few inflammatory cells. Both bone and fibrous tissue were seen at the LCP/CF-host tissue interface. The cross-sectional cortical area of the operated femur was slightly greater than that of the control femur in the 2-year follow-up. LCP/CF showed promising properties for high-load applications.     

Characterization of cell lines derived from hamster tumors induced with the BK virus

Summary Some of the properties of three continuous cell lines derived from BK virus-induced hamster tumors were examined. The cell lines hadin vitro growth characteristics of transformed cells. Morphologically most of the cells were fibroblastic, but multinucleated giant cells were also common. Ultrastructurally all three cell lines displayed the usual features of cells grownin vitro. Marked variation in the nuclear size and shape as well as prominent nucleoli were characteristic to these cells. No viruses or virus-like particles were found. Virus isolation attempts by fusing the cells with Vero cells were negative, and no virion antigen was detected in these cells by immunofluorescence. T antigen similar to that of other papovaviruses was found in the cells. This antigen stained with sera from a number of hamsters carrying transplanted BK virus-induced tumors, and also with SV 40 T antisera. The antigen disappeared after 30 minutes at 56° C. Cytogenetic analyses showed that the three cell lines were heteroploid with subtetraploid numbers of chromosomes. Chromosome abnormalities were also seen. All three cell lines induced sarcomatous tumors in adult hamsters after subcutaneous inoculation.With 4 Figures     

Absence of group II phospholipase A2, a Paneth cell marker, from the epididymis

Paneth cell-like metaplasia has been reported in the epithelium of the epididymis and prostatic adenocarcinomas. We studied the expression of group II phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2 gave negative results in all six cases but positive reaction for lysozyme. The results show that the cells of the Paneth cell-like metaplasia are not true Paneth cells.     

Poor survival of cementless Biomet total hip: a report on 1,047 hips from the Finnish Arthroplasty Register

In Finland, almost 50% of all hip replacements done after 1989 have been inserted without cement. Biomet components have been the most commonly used implants in cementless arthroplasties. Between 1985 and 1997, 4,300 prostheses were implanted because of primary osteoarthrosis. 4 different acetabular component designs have been identified as Biomet implants (Mallory-Head, Romanus, T-TAP, Universal) and were used in 1,047 hips. The 9-year survival of all arthroplasties using Biomet cups was only 65 (95% CI 61-69)% while that of arthroplasties using T-TAP-cups was only 58 (52-65)%. In contrast, the 7.5-year survival of arthroplasties using Romanus cups was 85 (79-91)%. The 98 (96-99)% 5-year survival of arthroplasties with Mallory-Head cups should be interpreted cautiously, since similar results of arthroplasties using the Universal cup with the same type of liner decline sharply to 93 (88-98)% only 1 year later. The poor survival of Biomet cementless prostheses in our series seems to be related to the poor survival of the cup. This finding was common to all metal shell designs using Hexloc liners. We recommend that Biomet cups with Hexloc liners should not be used and patients who have had them inserted should undergo regular clinical and radiographic follow-ups.     

Anandamide prodrugs. 1. Water-soluble phosphate esters of arachidonylethanolamide and R-methanandamide.

Phosphate esters of arachidonylethanolamide (AEA) and R-methanandamide were synthesized and evaluated as water-soluble prodrugs. Various physicochemical properties (pK(a), partition coefficient, aqueous solubility) were determined for the synthesized phosphate esters. The chemical stability of phosphate esters was determined at pH 7.4. In vitro enzymatic hydrolysis rates were determined in 10% liver homogenate, and in a pure enzyme-containing (alkaline phosphatase) solution at pH 7.4. The intraocular pressure (IOP) lowering properties of R-methanandamide phosphate ester were tested on normotensive rabbits. The phosphate promoiety increased the aqueous solubility of the parent compounds by more than 16500-fold at pH 7.4. Phosphate esters were stable in buffer solutions, but rapidly hydrolyzed to their parent compounds in alkaline phosphatase solution (t(1/2)<15 s) and liver homogenate (t(1/2)=8-9 min). The phosphate ester of R-methanandamide reduced IOP in rabbits. These results indicate that the phosphate esters of AEA and R-methanandamide are useful water-soluble prodrugs.