PubMed Health⌕ Search

Biomedical subjects

P Cattan

Publications and source records attributed to P Cattan.

At least 19 recordsLinked to original sources

[Minimally invasive esophagectomy: prospective evaluation of laparoscopic gastric mobilization].

OBJECTIVE: Esophagectomy carries high morbidity, mainly due to respiratory complications. In digestive surgery, postoperative outcome is generally improved by minimally invasive surgery. A prospective study was conducted to evaluate feasibility and postoperative outcome of minimally invasive esophagectomy (MIE). METHODS: From July 2001 to June 2004, 20 patients underwent esophagectomy with laparoscopic gastric mobilization (LGM) for squamous cell carcinoma (N=11), adenocarcinoma (N=7), Barrett's esophagus with high-grade dysplasia (N=1), and long peptic stricture (N=1). Tumours (N=19) were located on the cardia (N=5), on the lower third of the oesophagus (N=10), on the median third (N=3), and on the upper third (N=1). Following LGM, transthoracic (N=19) or transhiatal (N=1) oesophagectomy was performed. RESULTS: Complete LGM was achieved in all cases. Mean operative time for LGM was 197+/-48 minutes. In the 19 patients operated for tumours, 18 underwent R0 resection. Eleven patients (55%) developed postoperative complications, mainly (30%) respiratory. Intrathoracic anastomotic leakage occurred in 2 patients, with favourable outcome. Pylorospasm (N=1) was the only intraabdominal complication. One patient died (5%). CONCLUSION: Esophagectomy with LGM is feasible with few specific complications. However, no decrease in morbidity could be observed with this technique. Further studies are required to evaluate if thoracoscopy could improve the postoperative course after LGM and to validate oncologic safety of MIE.

Adenocarcinoma↗

Destruction of conditional insulinoma cell lines in NOD mice: a role for autoimmunity.

AIMS/HYPOTHESIS: betaTC-tet (H2(k)) is a conditional insulinoma cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Transgenic expression of several proteins implicated in the apoptotic pathways increase the resistance of betaTC-tet cells in vitro. We tested in vivo the sensitivity of the cells to rejection and the protective effect of genetic alterations in NOD mice. METHODS: betaTC-tet cells and genetically engineered lines expressing Bcl-2 (CDM3D), a dominant negative mutant of MyD88 or SOCS-1 were transplanted in diabetic female NOD mice or in male NOD mice with diabetes induced by high-dose streptozotocin. Survival of functional cell grafts in NOD-scid mice was also analyzed after transfer of splenocytes from diabetic NOD mice. Autoreactive T-cell hybridomas and splenocytes from diabetic NOD mice were stimulated by betaTC-tet cells. RESULTS: betaTC-tet cells and genetically engineered cell lines were all similarly rejected in diabetic NOD mice and in NOD-scid mice after splenocyte transfer. In 3- to 6-week-old male NOD mice treated with high-dose streptozotocin, the cells temporarily survived, in contrast with C57BL/6 mice treated with high-dose streptozotocin (indefinite survival) and untreated 3- to 6-week-old male NOD mice (rejection). The protective effect of high-dose streptozotocin was lost in older male NOD mice. betaTC-tet cells did not stimulate autoreactive T-cell hybridomas, but induced IL-2 secretion by splenocytes from diabetic NOD mice. CONCLUSION/INTERPRETATION: The autoimmune process seems to play an important role in the destruction of betaTC-tet cells in NOD mice. Genetic manipulations intended at increasing the resistance of beta cells were inefficient. Similar approaches should be tested in vivo as well as in vitro. High dose streptozotocin influences immune rejection and should be used with caution.

Animals↗

[Extensive digestive caustic burns: what are the limits for resection? A series of 12 patients].

AIM OF THE STUDY: To report the results of oesogastric resections extended to surrounding organs following caustic ingestion, and to precise indications for resection and results of reconstruction. PATIENTS AND METHODS: From 1988 to 2001, 12 patients underwent oesophago-gastrectomy, extended to duodenum and pancreatic head (n = 6), jejunum (n = 4), colon (n = 2), spleen (n = 2) or pancreatic body (n = 1). Early morbidity and mortality, specificities of reconstruction, and quality of oral feeding were assessed retrospectively. RESULTS: Mean intensive care unit stay was 50 days (range: 16-152 days). All patients developed complications. Six patients were reoperated for secondary extension of caustic burns, mainly to colon (n = 4), small bowel (n = 2) and pancreas (n = 2). Three patients died on postoperative days 17, 20, and 130. Secondarily, eight patients (75%) underwent a substernal right ileocoloplasty. Six patients (50%) survived initial resection, and esophageal reconstruction. After a mean follow-up of 35 months (range: 7-87 months), four patients (33%) eat normally. CONCLUSIONS: After caustic burn, oesogastric resections extended to surrounding organs are associated with high morbidity and mortality. However, return of normal oral feeding can be expected in 33% of cases. Secondary extension of caustic burns to adjacent organs is a common eventuality, and may lead to prompt reintervention. Massive injury to small bowel or colon may compromise digestive function or secondary esophageal reconstruction, and thus may be the reasonable limit for resection.

Adult↗

Cost of care for inpatients with community-acquired intra-abdominal infections.

Few studies have assessed the actual costs associated with failure of initial empiric antibiotic therapy administered to patients with community-acquired intra-abdominal infections. The goals of this study were (i) to determine the frequency of unsuccessful initial empiric therapy in a real-world setting and (ii) to determine the associated impact on medical costs. Thus, a retrospective chart review was performed at four acute-care university hospitals in France. A total of 292 patients hospitalized for community-acquired intra-abdominal infection were included. The mean age of the cohort was 51 years, and 42% of the patients were female. The most commonly administered empiric regimens were intravenous amoxicillin/clavulanate alone (69 patients) or in combination with other antibiotics ( n=87) and piperacillin/tazobactam alone ( n=24) or in combination ( n=48). Other regimens included broad-spectrum penicillin, cephalosporins, and fluoroquinolones administered alone or in combination ( n=64). Empiric therapy was successful in 189 (65%) patients and unsuccessful in 103 (35%). Among the 292 patients with community-acquired infection, 15 died of the infection, 8 required reoperation and 80 required second-line antibiotic therapy. Patients with unsuccessful initial empiric therapy had significantly more parenteral antibiotic days (10.3 vs. 7.6 days) and a longer length of stay (16.2 vs. 12.8 days) compared to those with successful initial empiric therapy. A better selection of initial empiric antibiotic therapy may significantly influence the medical costs associated with patients who are hospitalized with community-acquired intra-abdominal infections.

Adult↗

Fate of the rectum in patients undergoing total colectomy for Crohn's disease.

BACKGROUND: This study aimed to analyse disease recurrence and fate of the rectum in patients who had a total colectomy for Crohn's disease. METHODS: One hundred and forty-four patients who had a total colectomy for Crohn's colitis were reviewed retrospectively. Ileorectal anastomosis (IRA) was performed in 118 patients, while 26 never had an IRA after colectomy because of severe anorectal lesions. Factors associated with recurrence and rectal preservation failure were studied. RESULTS: The probability of clinical recurrence after IRA was 58 and 83 per cent at 5 and 10 years respectively. The probability of rectal preservation at 5 and 10 years was 70 and 63 per cent after colectomy, and 86 and 86 per cent after IRA, respectively. Patients with extraintestinal manifestation had a higher risk of recurrence and of rectal preservation failure. Previous ileal involvement was associated with a higher rate of ileal recurrence after IRA. After IRA, prophylactic treatment with 5-aminosalicylic acid was associated with a lower rate of recurrence and of failure to preserve the rectum. CONCLUSION: Overall, 63 per cent of patients had a functioning IRA 10 years after total colectomy. Absence of extraintestinal manifestation and prophylactic treatment with 5-aminosalicylates after IRA were the main factors associated with long-term rectal preservation.

Adolescent↗

Patterns of engraftment in different strains of immunodeficient mice reconstituted with human peripheral blood lymphocytes.

BACKGROUND: Models of immunodeficient mice reconstituted with a competent human immune system would represent an invaluable tool for the study of transplantation immunobiology allergy, autoimmunity, and infectious diseases. Severe combined immune deficiency (scid) mice can be successfully reconstituted with human peripheral blood lymphocytes (PBLs), but rates and levels of engraftment are poor. New strains of mice with diverse immunodeficiencies have been recently characterized or developed, which might prove to be advantageous for in vivo studies of human immune reactivity. METHODS: We have compared rates and patterns of human PBL engraftment in four available immunodeficient murine strains; scid-beige, nonobese diabetic (NOD)-scid, NOD-scid-beta2 m- and rag-. T- and B-lymphocyte engraftment, phenotype of engrafted cells, and occurrence of graft-versus-host disease (GVHD) were studied and compared. RESULTS: Successful engraftment of human PBL was readily obtained in the majority of scid-beige, NOD-scid, and NOD-scid-beta2 m- with a single i.p. administration of human PBLs, whereas it was seldom achieved in rag- animals. Human Ig levels were accordingly remarkably low in rag- recipients but, interestingly also in NOD-scid-beta2 m- mice. Engraftment was readily observed not only in peripheral blood but also in spleen and bone marrow of successfully reconstituted animals. Phenotypic analysis of engrafted human cells showed preserved CD4/CD8 ratios and a clear skewing toward an activated phenotype. GVHD was invariably observed in successfully reconstituted animals. CONCLUSIONS: Our data indicate that a high rate of reconstitution with human lymphocytes can be achieved in scid-beige, NOD-scid, and NOD-scid-beta2 m- mice. Human Ig are produced at high levels, except in NOD-scid-beta2 m-, including xenoreactive natural antibodies. Scid-beige and NOD-scid appear therefore better suited than NOD-scid-beta2 m- or rag- for analysis of human immunoreactivity in vivo. An important caveat is the invariable occurrence of GVHD that precludes long-term studies in this model system.

Animals↗

Early assessment of apoptosis in isolated islets of Langerhans.

BACKGROUND: There is substantial evidence to link early graft loss after islet transplantation to isolation-induced islet cell apoptosis. Measurement of caspase 3 activity and detection of the lost cell membrane asymmetry, revealed by annexin V binding, are newly available assays that allow the analysis of early events of apoptosis. METHODS: In this study, we compared these tests with the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and analysis of DNA fragmentation after gel electrophoresis in freshly isolated islets obtained from rats, before and after treatment with interleukin-1 beta, interferon gamma, and tumor necrosis factor a, cytokines known to induce islet cell damage. RESULTS: A measurable level of apoptosis was observed the day after isolation when caspase 3 activity and annexin V binding were used as assays, although no substantial DNA fragmentation was detected with TUNEL assay and DNA gel electrophoresis. Baseline caspase 3 activity was 0.8+/-0.3 U/100 islet equivalents and it increased to 1.4+/-0.45 U/100 islet equivalents 3 hr after cytokine stimulation (P<0.05 vs. unstimulated islets). The baseline level of apoptosis, as detected by annexin V binding, was 21.1%+/-5.8%, and it increased to 27.5%+/-8.1% 6 hr after addition of the cytokine cocktail (P<0.01 vs. unstimulated islets). An increase in the number of TUNEL-positive nuclei was detected 24 hr after stimulation and peaked at 48 hr. DNA laddering was also evident 24 hr after cytokine treatment. CONCLUSION: These data suggest that measurement of caspase 3 activity and annexin V binding analysis might represent reliable markers of early events of islet cell apoptosis.

Animals↗

Endotoxin-mediated delayed islet graft function is associated with increased intra-islet cytokine production and islet cell apoptosis.

BACKGROUND: Primary nonfunction resulting in immediate graft loss is responsible for the failure of a large number of islet transplants. Evidence is accumulating to single out endotoxin contamination of the various reagents needed for islet isolation as a major cause of early graft loss. METHODS: Islets isolated with endotoxin-containing (400 endotoxin units/ml) collagenase type V and "endotoxin-free" (3.1 endotoxin units/ml) Liberase were compared. Graft function was assessed using a syngeneic murine model of marginal islet mass transplantation. Pro-inflammatory cytokine production by islets was measured by ELISA in culture supernatants, and quantitative reverse transcriptase-PCR. Islet cell apoptosis was measured using the annexin assay. RESULTS: Graft function was significantly delayed when islets were isolated with endotoxin-containing collagenase. Addition of endotoxin to the Liberase solution similarly delayed graft function. After 18 hr in culture, collagenase-isolated islets released higher amounts of proinflammatory cytokines compared with Liberase-isolated islets (interleukin-6: 2,185+/-1,174 pg/ml vs. 520+/-201 pg/ml; tumor necrosis factor-alpha: 304+/-298 pg/ml vs. 0; IL-1beta: 12.5 pg/ml+/-12.5 vs. 0). This observation correlated with higher cytokine mRNA expression in collagenase-isolated islets. The percentage of apoptotic islet cells immediately after isolation was 17.2%+/-9.4 in collagenase-isolated islets and 7.1%+/-2.1 in Liberase-isolated islets. CONCLUSIONS: We propose that endotoxin contamination is the primum movens of a chain of events that involves intra-islet cytokine production and release and islet cell apoptosis, and endotoxin contamination can ultimately lead to primary nonfunction in vivo. This emphasizes the fact that using endotoxin-free reagents during isolation is a key factor for successful islet transplantation.

Animals↗

Prolonged islet graft survival in NOD mice by blockade of the CD40-CD154 pathway of T-cell costimulation.

Allorejection and recurrence of autoimmunity are the major barriers to transplantation of islets of Langerhans for the cure of type 1 diabetes in humans. CD40-CD154 (CD40 ligand) interaction blockade by the use of anti-CD154 monoclonal antibody (mAb) has shown efficacy in preventing allorejection in several models of organ and cell transplantation. Here we report the beneficial effect of the chronic administration of a hamster anti-murine CD154 mAb, MR1, in prolonging islet graft survival in NOD mice. We explored the transplantation of C57BL/6 islets into spontaneously diabetic NOD mice, a combination in which both allogeneic and autoimmune components are implicated in graft loss. Recipients were treated either with an irrelevant control antibody or with MR1. MR1 administration was effective in prolonging allograft survival, but did not provide permanent protection from diabetes recurrence. The autoimmune component of graft loss was studied in spontaneously diabetic NOD mice that received syngeneic islets from young male NOD mice. In this combination, a less dramatic yet substantial delay in diabetes recurrence was observed in the MR1-treated recipients when compared with the control group. Finally, the allogeneic component was explored by transplanting C57BL/6 islets into chemically induced diabetic male NOD mice. In this setting, long-term graft survival (>100 days) was achieved in MR1-treated mice, whereas control recipients rejected their grafts within 25 days. In conclusion, chronic blockade of CD154 results in permanent protection from allorejection and significantly delays recurrence of diabetes in NOD mice.

Animals↗

Heme oxygenase-1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation.

Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 upregulation in a beta-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 upregulation might result in improved success in islet transplantation.

Animals↗

Absence of CSF-1-dependent macrophages does not improve function of transplanted islets of Langerhans.

A role of macrophage-mediated inflammatory events in early islet graft loss is increasingly acknowledged. Osteopetrotic mice (op/op) have a complete absence of CSF-1, and thus of most tissue macrophages. We have investigated whether the absence of CSF-1-dependent macrophages in the graft itself or at the transplant site could decrease the delay to function of a syngeneic marginal islet mass. Islets transplanted into op/op or control recipients reversed diabetes in 59 days vs. 10 days (p = 0.28, NS). Islets isolated from op/op or control mice reversed diabetes in 11 days vs. 10 days. IL-1 and TNF-alpha release by cultured islets was markedly decreased for op/op islets compared with control islets (IL-1: 0 vs. 4.2 pg/ml, p = 0.07; TNF-alpha: 67 vs. 311 pg/ml, p = 0.002). In contrast, IL-6 release by op/op islets was significantly increased (11.1 vs. 4.3 ng/ml, p = 0.006). CSF-1-dependent tissue macrophages may not be critical in the inflammatory insult to islet transplants. Alternate patterns of intraislet release of deleterious proinflammatory cytokines may exist.

Animals↗

Reoperation for secondary uremic hyperparathyroidism: are technical difficulties influenced by initial surgical procedure?

BACKGROUND: Parathyroid surgery in patients with uremia and secondary hyperparathyroidism is performed either by subtotal parathyroidectomy or total parathyroidectomy with immediate reimplantation. The aim of this study was to compare the results of reoperation for persistent or recurrent hyperparathyroidism after parathyroidectomy according to which initial operative procedure was used. PATIENTS AND METHODS: Eighty-nine patients had reoperation for persistent (28 patients) or recurrent (61 patients) hyperparathyroidism after 53 subtotal parathyroidectomies and 36 total parathyroidectomies with immediate reimplantation. Results of the reoperation were assessed in terms of success rate, morbidity, and operative findings. RESULTS: The success rate of reoperation in patients with persistent hyperparathyroidism was 89% and was independent of the initial type of surgery. Success rates of reoperation for recurrent hyperparathyroidism after initial subtotal parathyroidectomy and total parathyroidectomy with immediate reimplantation were 87% and 70%, respectively (P = .02). Hypertrophy of the parathyroid remnant was the main cause of recurrence after subtotal parathyroidectomy. After total parathyroidectomy with immediate reimplantation, recurrence was located in the graft in half the patients, while hyperplastic tissue was found in the neck or the mediastinum in the other half. CONCLUSIONS: Subtotal parathyroidectomy provides the best conditions for successful reoperation in case of recurrent hyperparathyroidism and should become the surgical treatment of choice for secondary hyperparathyroidism.

Adult↗

Extensive abdominal surgery after caustic ingestion.

OBJECTIVE: To report the authors' experience in extensive abdominal surgery after caustic ingestion, and to clarify its indications. SUMMARY BACKGROUND DATA: After caustic ingestion, extension of corrosive injuries beyond the esophagus and stomach to the duodenum, jejunum, or adjacent abdominal organs is an uncommon but severe complication. The limit to which resection of the damaged organs can be reasonably performed is not clearly defined. METHODS: From 1988 to 1997, nine patients underwent esophagogastrectomy extended to the colon (n = 2), the small bowel (n = 2), the duodenopancreas (n = 4), the tail of the pancreas (n = 1), or the spleen (n = 1). Outcome was evaluated in terms of complications, death, and function after esophageal reconstruction. RESULTS: Five patients required reintervention in the postoperative period for extension of the caustic lesions. There were two postoperative deaths. Seven patients had secondary esophageal reconstruction 4 to 8 months (median 6 months) after initial resection. Three additional patients died 8, 24, and 32 months after the initial resection. Three survivors eat normally, and one has unexplained dysphagia. CONCLUSIONS: An aggressive surgical approach allows successful initial treatment of extended caustic injuries. Early surgical treatment is essential to improve the prognosis in these patients.

Adult↗

Successful surgical removal of occult metastases of medullary thyroid carcinoma recurrences with the help of immunoscintigraphy and radioimmunoguided surgery.

Patients with recurrent or metastatic medullary thyroid carcinoma (MTC) were referred for pretargeted immunoscintigraphy (Affinity Enhancement System; AES) and radioimmunoguided surgery (RIGS). Data collected from 13 patients establish that whole-body AES immunoscintigraphy revealed metastases < 360 mg and RIGS detected micrometastases (5-15 mg). All tissue samples removed by the surgeon were diagnosed by histology and immunohistochemistry of calcitonin to check the accuracy of IS and RIGS results. AES immunoscintigraphy is very sensitive. Of 34 metastases or recurrences detected, 22 had escaped physical examination or conventional imaging. The accuracy of RIGS was 86%, its sensitivity 75%, and its specificity was 90% (n = 208). IS and RIGS detected occult tumors that would have escaped surgery, clearly demonstrating clinical benefit. Serum calcitonin (normal, 10 pg/ml) and carcinoembryonic antigen (normal, 5 ng/ml) of two patients were restored to normal. In patients whose tumors were discovered, progression of their disease was slowed, as evidenced by the large decrease in serum calcitonin and carcinoembryonic antigen, an important prognostic factor. Surgery was canceled in one case where IS detected distant metastases out of surgical reach. Thus, AES immunoscintigraphy and RIGS might be of valuable help for the surgical management of medullary thyroid carcinoma.

Adult↗

[Pharyngo-esophagoplasty by right coloplasty for the treatment of post-caustic pharyngo-laryngeal-esophageal burns: a report of 13 cases].

We report a new technique of pharyngoesophagoplasty by right coloplasty, indicated in postcaustic severe pharyngeal stenosis, analyzing the anatomical and functional results in terms of respiratory tract and phonation as well as digestive tract outcome. We compared our results with those obtained with other procedures. Between March 1995 and September 1998, pharyngoesophagoplasty by right coloplasty was performed in 13 patients. All had severe hypopharyngeal stricture with total obliteration of the two piriform sinuses and the upper esophageal sphincter. Nine patients underwent emergency esophagectomy or esogastrectomy by stripping and four had a cicatricial esophagus. Eight patients underwent tracheotomy before the pharyngoplasty due to burns of the laryngeal margin or airway infections. There was no perioperative mortality. The retrospective analysis in February 1998 with a follow-up of 22 months disclosed two deaths, one from septic shock following pneumnia and one suicide. For the 11 other patients, respiratory function had been restored successfully as the tracheostomy tube had been removed. Eight of the patients were on regular oral diet and the jejunostomy tube had been removed. Three had mild dysphagia and the oral diet was supplemented by jejunostomy tube feedings. These results were most successful compared with those obtained with 29 other patients. Pharyngo-esophagoplasty by right colonic transposition appears to be the method of choice for the reconstruction of post-caustic pharyngeal and esophageal stenosis.

Adult↗