5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and Therapy: In Vitro Studies.

Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here, we report a new approach for the delivery of 5-ALA. Squalenoylation strategy was used to covalently conjugate 5-ALA to squalene, a natural precursor of cholesterol. 5-ALA-SQ nanoassemblies were formed by self-assembly in water. The nanoassemblies were monodisperse with average size of 70 nm, polydispersity index of 0.12, and ζ-potential of + 36 mV. They showed good stability over several weeks. The drug loading of 5-ALA was very high at 26%. In human prostate cancer cells PC3 and human glioblastoma cells U87MG, PpIX production was monitored in vitro upon the incubation with nanoassemblies. They were more efficient in generating PpIX-induced fluorescence in cancer cells compared to 5-ALA-Hex at 1.0 to 3.3 mM at short and long incubation times. Compared to 5-ALA, they showed superior fluorescence performance at 4 h which was diminished at 24 h. 5-ALA-SQ presents a novel nano-delivery platform with great potential for the systemic administration of 5-ALA.

[Could we trust clinical statistics from data banks of the National Health Service (NHS)?]. / Peut-on se fier aux statistiques fournies par les banques de données émanant du ministère de la santé?

Can we accept the statistics provided by the Ministry of Health, which uses large computerized databases? Through MEDECHO, the Ministry provides to hospital managers, reports cards on different interventions. These reports compare different hospitals performances. Surgeons involved in the process hesitate to accept this information. Using the results of the performance of cholecystectomy provided by this system (Gr: A), we compared the same cohort (1 April-31 December 1996 = 346 cholecystectomies) but using specific criteria determined as relevant to our surgeons (Gr: B). The rate of complication gives a crude aftermath and no attempt was used to adjust for severity. The MEDECHO data are adjusted for severity. The global rate of complications is similar Gr: A 11%, Gr: B 12%. Major complication rate for pulmonary embolism, hemorrhage and biliary duct trauma are identical. The rate of surgical site infection is higher in Gr: B (5% vs. 2%). The patients are seen in the outpatient clinic and these observations are not included by the analytical system unless the patient has been readmitted. For our hospital, the MEDECHO data are valid and reliable even though they underestimated the wound infection rate. These results could be explained by an appropriate interpretation of the code system by the archivist and by the surgeons' precision to complete the summary sheet of hospitalization. We can conclude that these data can be used as a means to evaluate the quality of outcome of a surgical service.

Determinants of late allograft nephrectomy.

When loss of graft function occurs more than six months after transplantation, allograft nephrectomy is not routinely performed at the time of graft failure. It is usually performed only on those patients who subsequently develop specific complications. However, little is known about the characteristics that make patients more likely to require allograft nephrectomy. The purpose of our study was to identify risk factors for the subsequent need for allograft nephrectomy in patients with graft failure occurring more than 6 months after transplantation. Forty-one patients were studied. Inclusion criteria were: loss of graft function > or = 6 months after transplantation, resumption of dialysis and initiation of weaning from immunosuppression. Thirty patients were treated with cyclosporine + prednisone +/- azathioprine and 11 with azathioprine + prednisone. Mean follow-up time was 17.8 months, ranging from 6 months to 6.1 years. Recipient age, sex and race, original renal disease, donor, donor source (cadaveric vs living related), HLA compatibility, levels of panel reactive antibodies, occurrence of initial delayed graft function, causes of graft failure and tapering of immunosuppression were similar in patients with and without allograft nephrectomy. Using univariate analysis, allograft nephrectomy was found to be significantly more frequent in patients with a history of 2 or more episodes of acute rejection than in patients with no rejection episode: 83% vs 30% (p = 0.03). In addition, allograft nephrectomy was found to be significantly more frequent if the immunosuppressive regimen included cyclosporine (62% vs 27.3%; p = 0.04). Using multivariate analysis however, the number of previous episodes of rejection was found to be the only significant predictor for allograft nephrectomy. None of the other variables considered in the multivariate analysis, including the type of immunosuppressive therapy, was identified as a significant predictor for the need to perform allograft nephrectomy. In summary, the need for late allograft nephrectomy was correlated with the number of previous episodes of acute rejection. Patients with a history of numerous rejection episodes should thus be considered more likely to require allograft nephrectomy once immunosuppression is withdrawn. Possible interventions to reduce or prevent the need for nephrectomy include more gradual tapering of immunosuppression at the time of graft failure or indefinite low-dose immunosuppressive therapy.

Spontaneous primary and secondary pneumothorax: a 10-year study of management alternatives.

OBJECTIVE: To study the outcome of conservative and surgical management of spontaneous pneumothorax. DESIGN: Retrospective study between January 1980 and December 1990, with a mean follow-up of 6.5 years. SETTING: A tertiary-care university hospital with a referral thoracic surgical unit. PATIENTS: All patients seen in the study period with spontaneous pneumothorax. Those with traumatic, iatrogenic or ventilator-associated pneumothoraces were excluded. There were 366 consecutive patients who had 508 episodes of spontaneous pneumothorax. Two hundred and thirty-nine patients had primary spontaneous pneumothorax (group 1); 127 had secondary spontaneous pneumothorax (group 2). INTERVENTIONS: Tube thoracostomy, apical resection with either pleurectomy or pleural abrasion. MAIN OUTCOME MEASURES: Recurrence and outcome after surgical management relative to recurrence, complications, operative technique and mean hospital stay were evaluated by clinical review and questionnaire by an independent observer. RESULTS: No significant differences were noted between the two groups with respect to the incidence of recurrent spontaneous pneumothorax after the first or second episode, and no significant differences were noted between the two operative techniques with respect to recurrence, complications, operative technique or death rate. However the mean hospital stay was doubled for group 2 patients (9.9 versus 4.3 days). CONCLUSIONS: Conservative treatment, including tube thoracostomy, was effective for primary and secondary spontaneous pneumothorax. Open surgery was effective in preventing recurrence in 95% of cases in both groups.

Surgical treatment of achalasia in a general hospital.

The authors report their experience with 43 patients treated for achalasia of the esophagus in a general hospital between 1971 and 1986. Patients were divided into two groups according to the type of surgery performed: group 1--29 patients treated by Heller myotomy, performed by nine general surgeons between 1971 and 1983; and group 2--14 patients treated by transthoracic Heller myotomy with the addition of a Belsey Mark-IV fundoplication. Dysphagia was reduced postoperatively in 82.6% of patients in group 1 and 92.8% of patients in group 2. Three patients in group 1 and one patient in group 2 had persistent dysphagia. Ten patients in group 1 had symptoms of gastroesophageal reflux (5 of them required a second antireflux procedure). In group 2, one patient had symptoms of gastroesophageal reflux, but was treated successfully medically. There was no difference in the degree of relief of dysphagia between the abdominal and thoracic approach, or in whether the operation was performed by a general surgeon without specific experience in the treatment of achalasia. The addition of a fundoplication to a Heller myotomy appeared to lessen the problem of postoperative gastroesophageal reflux. Since the Heller myotomy is technically difficult and may lead to obstruction of the poorly emptying esophagus the authors recommend that it be used selectively and only by the experienced esophageal surgeon.

[Palliative treatment of cancer of the esophagus using an endoluminal prosthesis]. / La palliation du cancer de l'oesophage par prothèse endoluminale.

Between 1973 and 1984, 27 patients with a cancer of the esophagus or the cardia and suffering dysphagia underwent palliation with an endoluminal prosthesis. Intubation under esophagoscopy or through a gastrotomy, or both, allowed the placement of 23 Celestin tubes and 4 Mousseau-Barbin prostheses. The early postoperative death rate was 11%. The overall morbidity was 37%. It included such complications as tube displacement (18.5% of patients), tracheal compression by the tube (7.4%), obstruction of the prosthesis (11%), esophageal fistula (7.4%), aspiration (7.4%) and wound infection (7.4%). The ability to swallow was acceptable in 24 patients.

Pancreatic trauma: a new diagnostic approach.

The difficulties encountered in the diagnosis of solitary pancreatic injury when there is no other indication for surgical exploration of the abdomen are discussed. We suggest that endoscopic transduodenal pancreatography is a reliable diagnostic tool of great help in evaluating such injuries with little morbidity.