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Biomedical subjects

Philippe Morel

Publications and source records attributed to Philippe Morel.

At least 73 records · Page 4Linked to original sources

Acute left colonic diverticulitis: can CT findings be used to predict recurrence?

OBJECTIVE: We explored CT and demographic predictors for unfavorable outcome of nonoperative treatment in patients with a first event of left colonic diverticulitis. MATERIALS AND METHODS: We retrospectively analyzed the medical files and CT scans of 312 consecutive patients who were diagnosed as having diverticulitis on an admission CT report or who had a final diagnosis of left colonic diverticulitis. Patients who did not undergo nonoperative treatment or were lost to follow-up (n = 144) were excluded from the study. Admission CT scans of 168 consecutive patients with a diagnosis of left colonic diverticulitis who underwent nonoperative treatment and had an 18-month follow-up were reassessed by three radiologists unaware of the clinical findings. Nonoperative treatment was defined as an attempt to treat the patient with only antibiotics without scheduling them for elective (delayed) surgery. Unfavorable outcome was defined as a failure of nonoperative treatment 18 months after admission that required either surgery or rehospitalization for antibiotic treatment. The risk of unfavorable outcome was modeled using logistic regression as a function of sex, age, and CT criteria including the maximum number of diverticula per 10 cm of colon; the presence of intraabdominal abscess or extraintestinal gas bubbles (< 5 mm diameter) or gas pockets (>or=5 mm); the length and location of the abnormal colonic segment; the maximum thickness of the colonic wall; the presence of associated free intraperitoneal fluid; and the extent of fatty infiltration. RESULTS: Among these 168 patients, 115 (68%) had an uneventful outcome, but nonoperative treatment failed in 53 (32%). The presence of an abscess (n = 19) or extraintestinal gas pocket (n = 14) were the only CT findings significantly associated with failure of nonoperative treatment. Adjusted odds ratios (95% confidence interval) for failure were 6.18 (1.76-21.68) when an abscess was diagnosed and 4.26 (1.04-17.57) when pockets of free air were observed. Sex and age were not significantly associated with unfavorable outcome of nonoperative treatment. CONCLUSION: Abscess and pockets of extraintestinal gas 5 mm in diameter or larger correlated with unfavorable outcome of nonoperative treatment. None of the other criteria evaluated were predictive of failure of nonoperative treatment, including bubbles of extraintestinal gas smaller than 5 mm in diameter.

Acute Disease↗

Cost analysis of human islet transplantation for the treatment of type 1 diabetes in the Swiss-French Consortium GRAGIL.

OBJECTIVE: To evaluate the cost of islet transplantation in type 1 diabetic patients with a functional renal graft in a multicenter network. RESEARCH DESIGN AND METHODS: The study involved nine diabetic patients transplanted in the Swiss-French Groupe Rhône-Alpes, Rhin et Geneve pour la transplantation d'Ilots Langerhans (GRAGIL) consortium between March 1999 and June 2000. The direct medical costs were estimated from Social Security's perspective from the inclusion of the patient to 1 year after transplantation. All cost components were computed separately and included evaluation, screening and candidacy, organ retrieval, islet processing, pancreas and islet transportation, hospitalization for transplantation, follow-up, medications (immunosuppressive, antidiabetic, and adjuvant drugs), and adverse events requiring hospitalization. RESULTS: During the study period, 56 pancreata were processed and 14 islet preparations were transplanted. The average cost of an islet transplantation (procedure and 1-year follow-up) was 77,745 euro (French rate, year 2000). The four main cost components were islet preparation (30% of the total cost), adverse events (24%), drugs (14%), and hospitalization (13%). CONCLUSIONS: Overall costs of islet transplantation are slightly higher than those of pancreas transplantation. The cell isolation process is a critical point; a reduction in overall cost will require more efficient ways of isolating high yields of viable islets. Costs generated by shipments within the GRAGIL network did not represent an economic burden. It can be expected that the costs will decrease with growing experience and improving technology.

Chemotherapy, Adjuvant↗

Squamous cell carcinoma of the anus: another sexually transmitted disease.

During the past 30 years, there has been remarkable progress in our understanding of the pathogenesis of squamous cell carcinoma of the anus. It is now accepted that anal cancer is a sexually transmitted disease, which can be cured using a combination of chemo- and radiotherapy. The biology of anal cancer remains to be elucidated, as do the molecular mechanisms involved in resistance to chemoradiation. The contribution of HIV infection to tumour progression currently represents an area of intensive investigation. Finally, the growing numbers of AIDS patients who experience prolonged survival represent a population at risk. In the future, cytological screening of male homosexuals with an anal Papanicolaou test may help in identifying high-grade dysplasia and preventing anal cancer.

Acquired Immunodeficiency Syndrome↗

Long term results after complete or incomplete surgical resection of liver hydatid disease.

BACKGROUND: The liver is the organ most frequently infected by hydatid disease and medical therapy alone is ineffective in eliminating the parasite. Surgical options vary from complete resection (e.g. total pericystectomy or hepatectomy) to limited procedures (e.g. percutaneous aspiration or unroofing of cysts). The aim of this study was to determine the long-term outcome after complete or partial resection of liver hydatid cysts. PATIENTS AND RESULTS: Between 1980 and 1996, 78 patients were operated upon at our institution for liver hydatid cysts. In Group 1, complete resection was achieved in 57 patients (73 %), whereas in Group 2, incomplete resection was performed in 21 patients (27 %), due to multiplicity, bilaterality of cysts or close contact between a cyst and portal or hepatic veins. The post-operative morbidity in Groups 1 and 2, was 31 % and 47 % (N.S.), respectively. Mean duration of hospital stay was 17 and 26 days (p=0.004), respectively. Recurrence rate of hydatid disease after a mean follow-up of 6.6 years was 0 % and 12% (N.S.), respectively. There was no mortality in either group. CONCLUSIONS: Complete surgical resection of hepatic hydatid disease should be attempted whenever possible. Our results, with a mean follow-up of 6.6 years, indicate limited post-operative debilitating complications, low recurrence rate and no mortality.

Adolescent↗

Intra-portal injection of 400- microm microcapsules in a large-animal model.

To date, encapsulated grafts have usually been implanted in the peritoneal cavity. This site is, however, not ideal, mainly because of its low blood supply. We have investigated the feasibility of intra-portal injection of (400 microm) microcapsules in the pig. Ten-thousand microcapsules per kilogram body weight were injected into six Large White pigs. Portal pressure, various biological tests, portographies and liver histology were recorded before and at various time points after injection. As a result, portal pressure increased after injection (15+/-2.3 vs 8.7+/-1.7 mmHg) but remained within an acceptable range (<20 mmHg) and returned to normal values at 3 months (8.5+/-3.7 mmHg). During the 3-month follow up, liver function and liver tests remained stable. Portographies showed a homogenous implantation of the capsule, with the portal flow always directed to the liver. At histological examination after 3 months the capsules demonstrated various degrees of fibrosis. We can thus conclude that these results demonstrate that intra-portal injection of microcapsules is feasible in a large-animal model. Hemodynamic, biological and radiological results are similar to those observed in clinical free-islet transplantation.

Animals↗

Hepatocellular adenoma and polycystic ovary syndrome.

Various identified risk factors predispose to hepatocellular adenomas. We present the case of a young woman with liver adenoma in a context of polycystic ovary syndrome, associated with high levels of androgens and following a high dose hormonal therapy. In view of this complication, we recommend a close screening of patients with such hormonal imbalance, especially those who are treated with high doses of hormones, with repeated liver tests and ultrasonographies.

Adenoma, Liver Cell↗

Kidney-pancreas transplantation in a long-term non-progressor HIV-infected recipient.

With the introduction of highly active antiretroviral therapy (HAART), HIV infection has become a chronic disease with more frequent end-stage organ failures. As a result, the question of transplantation in HIV patients is raised more often. Although still subject to controversies, HIV infection is no longer an absolute contraindication to solid organ transplantation. We report a case of combined kidney-pancreas transplantation in a HIV recipient. HIV has remained stable without any antiviral therapy for up to 2 years after transplantation and has reached criteria for inclusion in the long-term nonprogressor (LTNP) group. Grafted organs demonstrated good function without rejection. This case emphasizes the need to consider LTNP HIV patients as a specific subgroup, when discussing solid organ transplantation. HAART is not required, thus sparing drug interactions and their unique immunological features, such as CCR5 mutation, might prevent rejection. This subgroup of HIV patients should be offered less restricted access to transplantation.

Adult↗

Islet autotransplantation after left pancreatectomy for non-enucleable insulinoma.

Insulinoma is a rare, almost always benign endocrine tumor of the pancreas, clinically characterized by hyperinsulinemic, hypoglycemic episodes. Surgical excision is the therapy of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive pancreatic resection. We present the cases and the metabolic follow up of two patients, 81 and 73 years old, with insulinoma localized close to the main duct in the pancreatic neck. Both patients underwent an 80% left pancreatectomy, avoiding a pancreatico-enteric anastomosis. In order to prevent postpancreatectomy diabetes, the islets from the tumor-free part of the resected pancreas were isolated and injected via a right colic vein into the portal system. After a follow up of 6 and 3 years respectively, both patients remained insulin-independent without any dietary restrictions. Fasting and glucagon-stimulated C-peptide-levels and glycosylated hemoglobin remained within normal range. There were no signs of recurrent insulinoma. Liver biopsy performed in one patient at 1 year after autotransplantation, showed intact, insulin-producing islets within the portal spaces. In conclusion, autologous islet transplantation can preserve the insulin secretory reserve after extended left pancreatectomy for the treatment of benign tumors in the pancreatic neck.

Aged↗

Severe acute pancreatitis and reduced acinar cell apoptosis in the exocrine pancreas of mice deficient for the Cx32 gene.

BACKGROUND & AIMS: The early events leading to acinar cell injury during acute pancreatitis are poorly characterized. Signaling through gap junction channels contributes to the homeostasis of the exocrine pancreas by coordinating acinar cell activity within an acinus. To explore the role of gap junctional communication in acinar cell response to injury, we analyzed the course of acute pancreatitis induced by injection of cerulein in mice deficient for Cx32, the major gap junction protein expressed in the exocrine pancreas. METHODS: The severity of pancreatitis was evidenced by measuring serum amylase activity, pancreatic edema, acinar cell necrosis, pancreatic tumor necrosis factor alpha concentration, and myeloperoxidase activity. Acinar cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), caspase-3 activity, and Bax/Bcl-2 expression. Expression and function of connexin were evaluated by immunofluorescence and dye coupling. RESULTS: Cx32-deficient mice exhibited a deleterious course of acute pancreatitis with increased necrosis, edema, and inflammation of the exocrine pancreas. In addition, the exocrine pancreas of Cx32-deficient mice showed a decreased number of TUNEL-positive acinar cells and decreased caspase-3 activity but no change in Bax or Bcl-2 pancreatic expression. Interestingly, chemicals known to induce apoptosis in vivo had no effect on Cx32-deficient pancreatic acinar cells. CONCLUSIONS: Deficiency of a pancreatic connexin converts a mild reversible form of acute pancreatitis into a severe disease and decreases the sensitivity of acinar cells to apoptotic stimuli. The results show that acinar cell-to-cell communication plays a key role in the modulation of severity of acute pancreatitis.

Acute Disease↗

Role of macrophage inflammatory peptide-2 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

Acute pancreatitis is an inflammatory process of variable severity, and leukocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The effects of mediators released by these inflammatory cells may induce tissue damage. The aim of our study was to evaluate the role of the chemokine, macrophage inflammatory protein-2 (MIP-2), in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. The severity of pancreatitis was measured by serum amylase, pancreatic edema, acinar cell necrosis, and myeloperoxidase activity. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. To determine the role of MIP-2 in the pathophysiology of the disease, anti-MIP-2 antibody was administered either 1 hour before or 2 hours after the start of cerulein administration. MIP-2 concentrations increased in serum, pancreas, and lung tissues in mice treated with cerulein. Anti-MIP-2 antibody administrated either before or after cerulein partially protected against pancreas and lung injury. These results show that MIP-2 plays a key role in the pathophysiology of acute pancreatitis and that MIP-2 blockade may improve the outcome of the disease.

Acute Disease↗

Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. METHODS AND MATERIALS: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. RESULTS: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located < or = 6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). CONCLUSION: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a basis for additional investigation regarding RT dose escalation or the addition of concomitant chemotherapy.

Adult↗

Potential impact of in situ liver splitting on the number of available grafts.

BACKGROUND: The potential increase in the number of liver grafts gained from systematically using the technique of splitting optimal organs is still unknown. This study investigates the proportion of donors that should be considered for in situ split-liver harvesting according to strict criteria on which a consensus could be reached easily. METHODS: The records of 407 consecutive donors during a 4-year period in Switzerland were analyzed. Non-heart-beating donors and donors with missing data were excluded, leaving 338 donors as the study population. Liver splitting was considered feasible when the following criteria were met: age> or =14 and < or =50 years; weight> or =45 kg; body mass index< or =26 kg/m2; intensive care stay< or =3 days; mean arterial pressure> or =60 mm Hg; Na< or =160 mmol/L; serum glutamic pyruvic transaminase< or =60 U/L; gamma-glutamyl transpeptidase< or =50 U/L; no steatosis at ultrasonography. Organs from donors> or =70 kg were considered suitable for a split, producing organs for two adults. RESULTS: Fifty-two (15%) donors fulfilled all the conditions for a split-liver procedure, of whom 29 (8.6%) were donors for 2 adults. The number of donors suitable for splitting increased to 145 (43%) if donors with only one missing criterion were included (77 [23%] for 2 adults). CONCLUSION: Even if the technique is restricted to optimal donors, splitting could appreciably increase the number of liver grafts. A wider use of the technique could reduce the patient's time on the waiting list and the need for living-donor procedures, and should be encouraged.

Adolescent↗

Early prediction of acute pancreatitis: prospective study comparing computed tomography scans, Ranson, Glascow, Acute Physiology and Chronic Health Evaluation II scores, and various serum markers.

The aim of this study was to assess the predictability of the outcome of acute pancreatitis using the Ranson, Glascow, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, the computed tomography (CT) scan, and several serum markers. Altogether, 137 consecutive patients with acute pancreatitis confirmed by CT scan were prospectively included. Blood samples were obtained daily for 6 days. The predictive value of each parameter was studied by univariate and multivariate analyses comparing mild and severe pancreatitis. A total of 111 attacks were graded as mild (81%) and 26 as severe (19%). Ranson (p = 0.3) and APACHE II (p = 0.049) scores appeared insufficiently predictive in the univariate analysis. Pancreatic imaging by CT scan was insufficiently predictive (p > 0.05), whereas the presence of extrapancreatic fluid collections was more indicative of outcome (p <0.05). With the univariate analysis, the four most reliable serum markers were pancreatic amylase (p <0.001), neutrophil elastase (p <0.05), albumin (p <0.002), and C-reactive protein (p <0.001). Results became homogeneous when the CT results were added; serum albumin plus extrapancreatic fluid collections (negative predictive value 92%-96% and positive predictive value 67%-100%) comprised the best indicator of severity. None of the parameters tested achieved sufficient predictability when used alone. Serum albumin plus extrapancreatic fluid collections comprise the best indicator of severity at the time of admission.

APACHE↗