Predictors of decline in verbal fluency after frontal lobe epilepsy surgery.

Few studies have focused on language changes following frontal lobe epilepsy (FLE) surgery. The aim of the current study is to quantify the role of resection location and size in verbal fluency decline after FLE surgery and to examine its predictors. A retrospective chart review identified 36 adult patients who underwent FLE surgery. Verbal fluency was assessed using the Controlled Oral Word Association Test (COWAT). Nine (25%) of the patients had significant decline. Binary logistic regression incorporating side of resection and preoperative COWAT score significantly predicted decline and accounted for 25% of the variance. A trend was also noted for decliners to have higher postoperative seizure recurrence (p=0.067). There was no effect of size of resection. Patients undergoing FLE surgery are at risk of verbal fluency decline, especially if they have a high presurgical verbal fluency score, undergo a frontal lobe resection in the language dominant hemisphere, and have poor seizure outcome.

[Cancer and spirituality: does knowledge of disease affect the degree of faith?]. / Cancer et religiosité: la connaissance de la maladie affecte-elle le degré de la foi en Dieu?

OBJECTIVE: To measure the influence of knowledge of one's cancer on the degree of religious faith in patients Method: Questioning of 117 patients with cancer who were admitted to the oncology department of the Hôtel Dieu de France Hospital during the period from 24 November 2005 to 1 December 2005, and filling out of an Arabic version of the SCSORF questionnaire: the higher the score on this questionnaire, the more it indicates a high level of religious faith. RESULTS: We found a higher score in patients who knew about their disease than in those who did not (p<0.001), a higher score in women than in men (p<0.05), a higher score in Muslims than in Christians (p<0.01), but Christians had a higher score on the question concerning comfort in religious faith (p<0.001), a higher score in patients with relapse of their disease than those with no relapse (p<0.01), and a higher score in patients who were not taking benzodiazepines than in those who were taking them (p<0.05). We also found a positive correlation between education level and knowledge of the disease (p<0.05), a positive correlation between the time lapsed since diagnosis and the frequency of prayer (p<0.05), and a negative correlation between education and the preference for being in a group of people of the same faith (p<0.05). CONCLUSION: This study is the first to demonstrate that knowing one's cancer diagnosis is a factor that increases the degree of religious faith, independently of the everyday stress experienced by the patient. This underscores the importance of the patient's faith in better controlling the symptoms of the disease and the side effects of the treatments, with a reduction in the use of benzodiazepines.

A randomized comparison trial of case-based learning versus human patient simulation in medical student education.

OBJECTIVES: Human patient simulation (HPS), utilizing computerized, physiologically responding mannequins, has become the latest innovation in medical education. However, no substantive outcome data exist validating the advantage of HPS. The objective of this study was to evaluate the efficacy of simulation training as compared with case-based learning (CBL) among fourth-year medical students as measured by observable behavioral actions. METHODS: A chest pain curriculum was presented during a one-month mandatory emergency medicine clerkship in 2005. Each month, students were randomized to participate in either the CBL-based or the HPS-based module. All students participated in the same end-of-clerkship chest pain objective structured clinical examination that measured 43 behaviors. Three subscales were computed: history taking, acute coronary syndrome evaluation and management, and cardiac arrest management. Mean total and subscale scores were compared across groups using a multivariate analysis of variance, with significance assessed from Hotelling's T2 statistic. RESULTS: Students were randomly assigned to CBL (n = 52) or HPS (n = 50) groups. The groups were well balanced after random assignment, with no differences in mean age (26.7 years; range, 22-44 years), gender (male, 52.0%), or emergency medicine preference for specialty training (28.4%). Self-ratings of learning styles were similar overall: 54.9% were visual learners, 7.8% auditory learners, and 37.3% kinetic learners. Results of the multivariate analysis of variance indicated no significant effect (Hotelling's T2 [3,98] = 0.053; p = 0.164) of education modality (CBL or HPS) on any subscale or total score difference in performance. CONCLUSIONS: HPS training offers no advantage to CBL as measured by medical student performance on a chest pain objective structured clinical examination.

Semiautomatic macroencapsulation of fresh or cryopreserved porcine hepatocytes maintain their ability for treatment of acute liver failure.

We have previously demonstrated that fresh or cryopreserved xenogeneic hepatocytes manually macroencapsulated in AN69 polymer and transplanted intraperitoneally in rats were able to improve the survival rate after 95% hepatectomy without immunosuppression. In addition, we developed a semiautomatic device where porcine hepatocytes were coextruded with AN69 hydrogel in order to macroencapsulate large amounts of cells. The purpose of the present study was to 1) test whether transplanted porcine hepatocytes macroencapsulated in this device remained functional as evaluated by their ability to prevent death from acute liver failure, and 2) compare the efficiency of cryopreserved or freshly isolated hepatocytes. Fresh or cryopreserved porcine hepatocytes were macroencapsulated in the semiautomatic device by coextrusion in AN69 polymer in 2-m minitubes containing 6 x 10(7) cells. Acute liver failure was induced in rats by two-step 95% hepatectomy. At the time of completion of liver resection, rats were either not transplanted with minitubes (control group I, n = 13), or were implanted with two minitubes containing culture medium (control group II, n = 11), hepatocytes killed by heat treatment (control group III, n = 10), coextruded fresh hepatocytes (group IV, n = 11), or coextruded cryopreserved hepatocytes (group V, n = 11), without immunosuppression. The survival rate at day 7 was between 0% and 31% in the three control groups. By contrast, coextruded fresh hepatocytes significantly improved the survival rate (group IV, 82%) as did cryopreserved cells (group V, 91% survival). In surviving rats, minitubes were explanted after 20 days; either fresh or cryopreserved hepatocytes appeared morphologically viable and their ultrastructure was preserved. Their detoxification capacities evaluated by the activity of the cyt P450 CYP3A4 were partly maintained. In conclusion, porcine hepatocytes macroencapsulated by coextrusion using a semiautomatic device and transplanted without immunosuppression were able to prevent death from acute liver failure in rats. Cryopreserved cells were as efficient as fresh hepatocytes.

Survival and differentiation of porcine hepatocytes encapsulated by semiautomatic device and allotransplanted in large number without immunosuppression.

BACKGROUND/AIMS: The aim of this study was to evaluate the survival and functions of porcine hepatocytes transplanted in large quantities in the peritoneal cavity of allogeneic animals following semiautomatic encapsulation. METHODS: Isolated porcine hepatocytes and a polymer solution composed of AN69 were coextruded through a double lumen spinneret. Minitubes containing hepatocytes were transplanted in the peritoneal cavity of 12 pigs (4 x 10(9) cells/animal) in the absence of immunosuppressive therapy. Seven, 15, and 21 days after transplantation, minitubes was collected and processed for analyses. The morphology was examined under light and electron microscopy. Albumin synthesis was assessed by semi-quantitative reverse transcription-polymerase chain reaction. Cytochrome P450 3A (CYP3A) gene expression was analyzed by Western blot and by testosterone 6-beta-hydroxylation assay. RESULTS: The device allowed to encapsulate 55 x 10(6) hepatocytes/min. Hepatocytes exhibited normal structural and ultrastructural features up to day 21. Albumin gene expression decreased progressively between days 0 and 21. The amount of CYP3A protein and 6-beta-hydroxylase activity were approximately 2-fold lower at days 7 and 15 than in freshly encapsulated hepatocytes, and further decreased thereafter. CONCLUSIONS: The preservation of hepatocyte functions during 1-2 weeks is encouraging for potential short-term use of such bioartificial liver in future clinical application.

Survival and functions of encapsulated porcine hepatocytes after allotransplantation or xenotransplantation without immunosuppression.

BACKGROUND: This study evaluated the survival and functions of encapsulated porcine hepatocytes after intraperitoneal allotransplantation and xenotransplantation without immunosuppression. METHODS: Isolated porcine hepatocytes were encapsulated in AN 69 polymer capsules (45.10(6)/capsule) and transplanted intraperitoneally in 12 rats and 12 pigs. Fifteen, 30, and 60 days after transplantation, capsules were removed and the viability and morphology of explanted hepatocytes were examined under light and electronic microscopy. The potential to produce albumin was assessed by evaluating the level of albumin messenger RNA, using semiquantitative reverse transcription-polymerase chain reaction. 6beta-Hydroxylase activity was measured by high-performance liquid chromatography. In addition, cytochrome P450 3A proteins were detected by Western blot only in allogeneic hepatocytes. RESULTS: Similar results were observed after allotransplantation and xenotransplantation. Histologic studies showed that hepatocytes were well-preserved and arranged in cords for up to 30 days. The expression of porcine albumin gene was maintained up to 15 days. 6beta-Hydroxylase activity was 2.5-fold lower at day 15 than in freshly encapsulated hepatocytes, which were not transplanted. In allogeneic hepatocytes, the expression of CYP 3A protein was detected up to 60 days after transplantation. CONCLUSIONS: Encapsulated porcine hepatocytes remain viable and functional for at least 15 days after allotransplantation and xenotransplantation without immunosuppression. The demonstration of maintained hepatic functions in transplanted porcine hepatocytes up to 15 days is a first step toward application in the treatment of acute liver failure.

Transplanted cryopreserved encapsulated porcine hepatocytes are as effective as fresh hepatocytes in preventing death from acute liver failure in rats.

BACKGROUND: An implantable bioartificial liver (BAL) using xenogeneic isolated hepatocytes may be an alternative method to orthotopic liver transplantation for treatment of acute liver failure. The purpose of this study was to demonstrate that not only fresh but also cryopreserved porcine hepatocytes could be used in a BAL to prevent death after the onset of acute liver failure in rats. METHODS: Acute liver failure was induced by two-stage 95% hepatectomy. At the time of completion of liver resection, 100 rats were assigned to undergo or not undergo transplantation into the peritoneum of 4 meters of hollow fibers filled with 60 million either fresh or cryopreserved porcine hepatocytes, or syngeneic hepatocytes, or culture medium, or of 60 million nonencapsulated cryopreserved porcine hepatocytes without immunosuppressive therapy. Survival rates at 7 days were compared between the different groups. RESULTS: In the control groups of hepatectomized animals not receiving encapsulated hepatocytes, 69-79% of the rats died from acute liver failure. The mortality rate was reduced to 15% (2 of 13) in rats receiving fresh porcine hepatocytes (P<0.01), 25% (4 of 16) in rats transplanted with either cryopreserved or syngeneic hepatocytes (P<0.05). Survival rates were maintained when hollow fibers were explanted > or =4 days after hepatectomy. In surviving rats, the weight of the remnant native liver increased with time and returned to the initial weight after 1 month. CONCLUSIONS: The implantable BAL using xenogeneic porcine hepatocytes was able in preventing death from acute liver failure without immunosuppressive therapy. Encapsulated cryopreserved hepatocytes were as effective as fresh hepatocytes.

Results of coloanal anastomosis for rectal cancer.

It is now accepted that, in the absence of direct invasion of the anal sphincter, cancers of the middle and lower rectum can be successfully treated with sphincter-preserving surgery. Conservation of the sphincter mechanism should never compromise the oncologic outcome of surgery and the method of neorectum construction must provide acceptable function for patients. This review describes the results of coloanal anastomosis following rectal excision. The oncological and functional results of both straight coloanal and colonic-J-pouch anal anastomosis are presented in detail. The authors discuss recent evidence supporting the functional superiority of colonic-J-pouch reconstruction after rectal excision.

Semiautomatic macroencapsulation of large numbers of porcine hepatocytes by coextrusion with a solution of AN69 polymer.

We have previously demonstrated that allogenic and xenogenic hepatocytes macroencapsulated manually in AN-69 polymer and transplanted intra-peritoneally in rats remained viable for several weeks. However, this manual technique is inadequate to encapsulate several billions of hepatocytes which would be required to correct hepatic failure in big animals or humans. In the present study, we developed an original semiautomatic device in which isolated pig hepatocytes and the polymer solution containing 6% poly(acrylonitrile-sodium methallylsulfonate), 91% dimethylsulfoxide and 3% 0.9% NaCl solution were coextruded through a double-lumen spinneret. The extruded minitube (inner diameter: 1.8 mm, wall thickness: 0.07-0.1 mm) containing the encapsulated hepatocytes fell and coiled up in a 0.9% NaCl solution at 4 degrees C and was cut down in 4 m units containing about 120 million hepatocytes. This process allowed to encapsulate 50 million hepatocytes by minute with a preserved immediate cell viability (92 +/- 5%). To test prolonged cell viability after coextrusion, the minitubes were implanted intraperitoneally in rats. Three and seven days after implantation, they were explanted and analyzed. Cells were viable and well-preserved. Therefore, the semiautomatic device appears able to efficiently macroencapsulate in a limited time several billions of porcine hepatocytes which remain viable after transplantation in xenogenic conditions.

[Viability and differentiation of human hepatocytes immunoprotected by macroencapsulation and transplanted in rats]. / Viabilité et état de différenciation des hépatocytes humains immunoprotégés par macroencapsulation et transplantés chez le rat.

OBJECTIVES: To determine the viability and differentiation of human hepatocytes immunoprotected by encapsulation and transplanted in rats without immunosuppression. METHODS: Freshly isolated human hepatocytes were encapsulated in hollow fibers and transplanted in the peritoneal cavity of immunocompetent rats. The fibers were explanted for analysis at D3, D7 and D14 following transplantation. Morphological features under light and electron microscopy and gene expression were compared to those of non-transplanted encapsulated hepatocytes (D0). Human cytochrome P450 3A and albumin mRNAs were quantified by Northern blot. Cytochrome P450 3A proteins were detected by Western blot and cytochrome P450 3A enzyme activity was assessed by measuring the formation of 6beta-hydroxytestosterone by high performance liquid chromatography. RESULTS: Transplanted hepatocytes were more than 60 % viable and exhibited morphological criteria of hepatocytic differentiation up to D7. Albumin and cytochrome P450 3A transcripts were also detected up to D14. At D3 and D7, albumin mRNA levels were of 30 %, compared to control D0 hepatocytes, while cytochrome P450 3A5 and cytochrome P450 3A4 mRNA levels were 65 % and 0 %, respectively. Cytochrome P450 3A immunoreactivity was detected by Western blot up to D14 and 6beta-hydroxylase activity was 17 % at D3 compared to D0, supporting with disappearance of cytochrome P450 3A4 mRNA. CONCLUSIONS: Human hepatocytes remain viable for a short period, following encapsulation and intraperitoneal transplantation in rat. Other experimental conditions need to be tested to prevent or delay a decrease in hepatocyte specific gene expression.

A reversible model of acute hepatic failure by temporary hepatic ischemia in the pig.

BACKGROUND: To evaluate new therapies for human fulminant hepatic failure, a suitable large animal model is needed. The purpose of this study was to develop a reversible surgical model of acute hepatic liver failure by transient ischemia in pigs. MATERIALS AND METHODS: Under general anesthesia, an end-to-side portacaval shunt was performed in 17 pigs and tape was laid around the hepatoduodenal ligament. Two days after construction of the functional portacaval shunt, 13 ambulant pigs underwent transient total liver ischemia by tightening of the tape around the hepatoduodenal ligament for 5.5 h. During ischemia, 10% glucose was continuously infused intravenously to prevent hypoglycemia. RESULTS: Ten animals (77%) died with hepatic coma after a mean duration of 22.5 +/- 1.9 h. The 3 remaining animals survived more than 5 days and were sacrificed. In dying animals, encephalopathy was observed 14 +/- 1.7 h after the onset of ischemia. During ischemia, similar progressive decrease of fibrinogen, platelets, prothrombin time, and factors V and VII activities was observed in dying and surviving animals. Just before death, mean prothrombin and factors V and VII activities were respectively 22 +/- 2, 21 +/- 4.4, and 24 +/- 5%. At 22 h, plasma ammonia and lactate levels were respectively 705 +/- 93 micromol/L and 10.5 +/- 0.4 mmol/L in dying animals and 249 +/- 75 micromol/L and 2.9 +/- 0.1 mmol/L in surviving animals (P < 0.01). Estimation of the percentage liver cells necrosed was 74 +/- 4.7% in the survivors and 86 +/- 5.5% in animals who died of hepatic coma (NS). CONCLUSIONS: This model is reproducible and reversible and should allow the quantitative evaluation of new technologies, such as bioartificial liver, for the support of hepatic failure in humans.

Anastomic dehiscence and severe peritonitis.

Fifteen years of experience in the management of postoperative complications following GI surgery are reviewed. In the surgical ICU of the Hôpital Saint Antoine, Paris, France, a referral center for these conditions, 385 cases of postoperative peritonitis and 500 cases of enterocutaneous fistulas were observed from 1980 to 1995. Original techniques of management are described in surgical treatment: temporary stomas, intubation irrigation of leaks situated on the upper GI tract, primary closure of the abdominal wall without tension. New methods of intensive care of intestinal conditions have also been designed: control and/or obturation of complex enterocutaneous fistulas, reinfusion of chyme into the distal small bowel and continuous enteral nutrition. In accordance with their experience in this field, the authors review the most controversial points of surgical technique and intensive care.

[Intraperitoneal transplantation of isolated hepatocytes of the pig: the implantable bioartificial liver]. / Transplantation intrapéritonéale d'hépatocytes isolés de porc: le foie bioartificiel implantable.

The general aim is to prepare a bioartificial liver to treat acute hepatic failure using allo- and xenogeneic hepatocytes, immunoprotected by macroencapsulation and transplanted into the peritoneal cavity. The goal of this study was to prepare a large amount of isolated porcine hepatocytes, to encapsulate them within biocompatible membranes for transplant in allo- and xenogeneic combinations and to examine the viability and functionality of the cells 6 weeks later. Hepatocyte isolation was performed in 12 kg pigs (n = 15) by dissociation of the liver with collagenase D (1 g) without oxygenation. Encapsulation of the hepatocyte suspension (10(7)/mL) was performed in hydrogel membranes AN69; hollow fibers (2 m x 0.8 mm) and flaskes (1.8 cm), and transplanted to Yucatan pigs (n = 4) and Lewis rats (n = 12). Six weeks later, they were removed to study the cell viability by histological examination, and the production of albumin by immunonephelometry. The rate of isolated hepatocytes was 38 +/- 5 x 10(9)/mL by liver of pig and the mean viability was 93 +/- 2%. Six weeks after transplantation, hepatocytes were viable, organized in lobules, and showed conserved albumin production. The same results were observed for allogenic and xenogeneic combinations. In conclusion, this method of liver dissociation allowed for preparation of a large amount of isolated hepatocytes from a single pig liver, theoretically sufficient to treat a patient with acute liver failure. Hydrogel membranes were well tolerated and allowed immunoprotection without immunosuppression. Transplanted hepatocytes remained functional. This work is an important step in progress toward clinical application.

[Metastatic implants after laparoscopic cholecystectomy in unsuspected gallbladder cancer. A case report and review of the literature]. / Implants métastatiques apres cholécystectomie laparoscopique d'un cancer non suspecté de la vésicule biliaire. Rapport d'un cas et revue de la littérature.

A gallbladder carcinoma, diagnosed preoperatively, is a counter-indication for laparoscopic cholecystectomy. When this cancer is not diagnosed and laparoscopic surgery is undertaken, neoplastic dissemination may occur along the trocars pathways which renders the prognosis even worse. The most probable explanation of the dissemination is a seeding of sloughed cancerous cells onto abdominal wall during exsuflation. The authors report the case of a 36-year-old woman with an adenocarcinoma of the gallbladder discovered after laparoscopic cholecystectomy and who has had rapid intra-abdominal and parietal metastases.

[The place of enucleation in the surgical management of hepatic hemangioma. Report of a case and review of the literature]. / Place de l'énucleation dans le traitement chirurgical de l'hémangiome hépatique. Rapport d'un cas et revue de la littérature.

Hepatic hemangioma is the most frequent benign tumor of the liver. It is often asymptomatic. If surgery is needed the best method will be enucleation of the hemangioma. We report a case of enucleation of a cavernous hepatic hemangioma with review of the literature.