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Biomedical subjects

M Gillet

Publications and source records attributed to M Gillet.

At least 19 recordsLinked to original sources

Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients.

BACKGROUND: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. PATIENTS AND METHODS: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. RESULTS: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. CONCLUSIONS: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.

Adult↗

[Rupture of hepatic focal nodular hyperplasia. About two cases].

The diagnostics of focal nodular hyperplasia is reached through the use of imaging. When the diagnostic is certain, surgical abstention is the rule. Nevertheless, we were confronted with two cases of a rare complication; that of intraperitoneal rupture. In this situation, we suggest to first do an arteriography to control the bleeding, then to perform surgery when the patient has reached hemodynamic stability. Spontaneous rupture as a complication of benign nodular hyperplasia remains a rare event and only five cases were reported in litterature.

Adult↗

Impaired insulin response after oral but not intravenous glucose in heart- and liver-transplant recipients.

BACKGROUND: The prevalence of diabetes is high after transplantation. We hypothesized that liver transplantation induces additional alterations of glucose homeostasis because of liver denervation. METHODS: Nondiabetic patients with a heart (n=9) or liver (n=9) transplant and healthy subjects (n=8) were assessed using a two-step hyperglycemic clamp (7.5 and 10 mmol/L). Thereafter, an oral glucose load (0.65 g/kg fat free mass) was administered while glucose was clamped at 10 mmol/L. Glucose appearance from the gut was calculated as the difference between glucose appearance (6,6 2H2 glucose) and exogenous glucose infusion. Plasma insulin, glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide(GIP) concentrations were compared after intravenous and oral glucose. RESULTS: After oral glucose, the glucose appearance from the gut was increased 52% and 81% in liver- and heart-transplant recipients (P<0.05). First-pass splanchnic glucose uptake was reduced by 39% in liver-transplant and 64% in heart-transplant patients (P<0.05). After oral but not intravenous glucose, there was an impairment of insulin secretion in both transplant groups relative to the controls. Plasma concentrations of GIP and GLP-1 increased similarly in all three groups after oral glucose. CONCLUSIONS: First-pass hepatic glucose extraction is decreased after heart and liver transplant. Insulin secretion elicited by oral, but not intravenous glucose, is significantly reduced in both groups of patients. There was no difference between liver- and heart-transplant recipients, indicating that hepatic denervation was not involved. These data suggest an impairment in the beta-cell response to neural factors or incretin hormones secondary to immunosuppressive treatment.

Administration, Oral↗

[Agenesis of the gallbladder].

Isolated agenesis of the gallbladder (AG) is a rare anomaly. Twenty-three percent of the patients are symptomatic and present with right upper abdominal pain, nausea and fatty food intolerance. The condition is frequently mistaken with excluded or sclero-atrophic gallbladder, regardless of the imaging modality used. Consequently, AG leads often to unnecessary and potentially dangerous surgery. During laparoscopy, the absence of normal anatomical structures and the impossibility of pulling on the gallbladder to dissect the triangle of Callot represent an increased risk of iatrogenic injury to biliary or portal structures. The aim of this study is to discuss the pitfalls of the available radiological exams and the management of this rare condition. We describe two cases of AG, with a review of the literature. A high index of suspicion is necessary when interpreting the radiological images. In case of doubt, a MRI-cholangiography is mandatory. Because of possible inherited transmission, relatives with a history of biliary symptoms should be investigated, even when asymptomatic.

Adult↗

Cystic pneumatosis of the colon after liver transplantation.

Cystic pneumatosis (CP) is an uncommon but significant condition in adults in which gas is found in a linear or cystic form in the submucosa or the subserosa of the bowel wall. The diagnosis was made by conventional X-ray and confirmed by abdominal computed tomography. Benign pneumoperitoneum due to CP should be considered in the differential diagnosis of free intra-abdominal air after chemotherapeutic or immunosuppressive therapy. As such, pneumatosis intestinalis is only a sign and must be interpreted in light of the clinical findings because it may be found in various scenarios: in patients who are otherwise healthy, and associated with pyloric stenosis, jejunoileal bypass, progressive systemic sclerosis, transplantation, chemotherapy, immunosuppression (including AIDS), obstructive pulmonary disease and finally, as in our case, after liver transplantation. Since there were no signs of secondary complications such as peritonitis, ischemia, or perforation, conservative treatment with broad-spectrum antibiotics and parenteral nutrition was initiated.

Adult↗

[Should benign tumors of the liver be operated?].

OBJECTIVES: To define a strategy for benign liver tumours treatment and to report our experience. DESIGN: A retrospective study. PATIENTS: Sixty-eight patients operated for benign liver tumours among 424 operated of liver resection. RESULTS: Benign liver tumours were discovered during radiologic exploration for upper abdominal pain in 69%, incidentally during radiologic examination in 23% or at laparotomy in 8% of patients. Preoperative assessment of solid benign liver tumours was based on 4 radiologic examinations in average whereas cystic lesions needed only 2. The surgical treatment ranged from a simple tumorectomy to liver transplantation depending on the type, size and location of the tumour. There were no postoperative deaths and minor complications occurred in 7 patients (10%). Twenty hemangiomas, 20 hepatic cysts, 22 focal nodular hyperplasias (FNH), 4 hepatic adenomas (HA) and 2 cystadenomas were found on histology. The final diagnosis differed from the preoperative one in 36 patients (53%). CONCLUSIONS: Differential diagnosis for cystic lesions are the hepatic cyst, the hydatid cyst and the cystadenoma. Hydatid cysts and cystadenomas are resected whereas the asymptomatic hepatic cyst is left untreated. Hemangiomas must be resected only when symptomatic or pedunculated. The differentiation between FNH, HA and hepatocellular carcinoma is difficult and final diagnosis is most often achieved only by surgery.

Adult↗

Effects of a glucose meal on energy metabolism in patients with cirrhosis before and after liver transplantation.

HYPOTHESIS: Liver transplantation results in hepatic denervation. This may produce alterations of liver energy and substrate metabolism, which may contribute to weight gain after liver transplantation. DESIGN: Prospective clinical study. SETTING: Liver transplantation clinics in a university hospital. PATIENTS: Seven nondiabetic patients with cirrhosis were recruited while on a waiting list for liver transplantation. Seven healthy subjects were recruited as controls. INTERVENTION: Orthotopic liver transplantation. MAIN OUTCOME MEASURES: Evaluation of energy and substrate metabolism after ingestion of a glucose load with indirect calorimetry was performed before, 2 to 6 weeks after, and 5 to 19 months after transplantation. Whole-body glucose oxidation and storage and glucose-induced thermogenesis were calculated. RESULTS: Patients with cirrhosis had modestly elevated resting energy expenditure and normal glucose-induced thermogenesis and postprandial glucose oxidation and storage. These measures remained unchanged after liver transplantation despite a significant increase in postprandial glycemia. Patients, however, gained an average of 3 kg of body weight after 5 to 19 months compared with their weight before transplantation. CONCLUSION: Liver denervation secondary to transplantation does not lead to alterations of energy metabolism after ingestion of a glucose load.

Blood Glucose↗

Malacoplakia simulating organ invasion in a rectosigmoid adenocarcinoma: report of a case.

Malacoplakia is a histiocytic inflammatory response that may be associated with colorectal tumors. We report the case of a 65-year-old male taking steroids for a severe pulmonary disease. He presented with a rectosigmoid tumor that seemed to infiltrate the urinary bladder and the sacrum on the preoperative CT scan and echography and at laparotomy. A low anterior resection en bloc with a partial cystectomy was performed. The pathologic analysis showed a pT3pN0 adenocarcinoma with an extensive malacoplakia infiltrating the bladder and the pericolic and perirectal tissues. This case report emphasizes the overstaging that malacoplakia may induce and underlines a situation the surgeon may possibly confront. Our observation confirms the association of malacoplakia, colorectal carcinoma, and steroid treatment.

Abdominal Pain↗

Esophageal cancer as second primary tumor after breast cancer radiotherapy.

BACKGROUND: An increased risk of esophageal cancer has been reported in survivors of breast cancer treated with radiotherapy. This study further characterizes this association. METHODS: Through hospital databases, 118 patients (109 men, 9 women) treated for esophageal cancer between 1985 and 1993 were identified, of whom 37 had 60 synchronous or metachronous cancers. 5 women had primary esophageal cancer after having breast cancer, and are the subjects of this case-control study. RESULTS: All 5 women had been treated with radical mastectomy and adjuvant radiotherapy; none received chemotherapy. Their ages at the time of breast cancer ranged from 36 to 82 years; at esophageal cancer, 61 to 95 years. Time between radiotherapy and esophageal cancer varied from 13 to 31 years. All esophageal cancers were squamous cell carcinomas. Mean survival after esophageal cancer was 14.2 months. CONCLUSIONS: Radio-induced esophageal cancer can occur as a second primary cancer in women who survive at least 1 decade after mastectomy and adjuvant radiotherapy.

Adult↗

Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer.

The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated in many human cancers. The aim of this study was to evaluate p14ARF and p16INK4a gene inactivation and its association with some clinocopathological parameters in colon cancer. The mutational and methylation status of the p14ARF and p16INK4a genes was analyzed in 60 primary colon carcinomas and 8 colon cancer cell lines. We have identified the first two reported mutations affecting exon 1beta of p14ARF in the HCT116 cell line and in one of the primary colon carcinomas. Both mutations occur within the N-terminal region of p14ARF, documented as important for nucleolar localization and interaction with Mdm2. Tumor-specific methylation of the p14ARF and p16INK4a genes was found in 33% and 32% of primary colon carcinomas, respectively. Methylation of the p14ARF was inversely correlated with p53 overexpression (p = 0.02). p14ARF and p16INK4a gene methylation was significantly more frequent in right-sided than in left-sided tumors (p = 0.02). Methylation of the p14ARF gene occurred more frequently in well-differentiated adenocarcinomas (p = 0.005), whereas the p16INK4a gene was more often methylated in poorly differentiated adenocarcinomas (p = 0.002). The present results underline the role of p14ARF and p16INK4a gene inactivation in the development of colon carcinoma. They suggest that the methylation profile of specific genes, in particular p14ARF and p16INK4a, might be related to biologically distinct subsets of colon carcinomas and possibly to different tumorigenic pathways.

Adaptor Proteins, Signal Transducing↗

Laparoscopic treatment of acute small bowel obstruction: a multicentre retrospective study.

BACKGROUND: Laparoscopic surgery is thought to promote early recovery and quicker return to bowel function. The objective was to evaluate the rate and predictive factors of success, the causes of failure, the morbidity, and mortality during and after hospitalization, as well as to determine whether laparoscopic treatment of acute small bowel obstruction offers the same benefits as for other laparoscopic procedures. METHODS: The records of 308 patients with acute small bowel obstruction treated laparoscopically in 35 centres between 1 October 1988 and 30 September 1996 were retrospectively reviewed. RESULTS: Treatment was implemented completely by laparoscopy ('success' group) in 168 patients (54.6%). Conversion to laparotomy ('failure' group) was required in 140 patients (45.4%; during the same operation in 126 patients and after a median delay of 4 days (range: 1-12 days) in 14 patients). There were significantly more successes in patients with a history of one or two surgical interventions than in those with more than two (56% vs 37%; P < 0.05). There were significantly more successes in patients who had undergone appendectomy only (67/94; 71%) than in patients who (i) had no antecedent surgery (52%; P < 0.05), or (ii) underwent other surgery (33%; P < 0.001). The rate of success was significantly higher (P < 0.001) in patients operated on early (< 24 h) and in patients with bands (54%), than in those with adhesions (31%) or with other causes of obstruction (15%). The median duration of postoperative ileus was significantly shorter in the 'success' group than in the 'failure' group (2 days vs 4 days; P < 0.001). The median duration of postoperative hospital stay was shorter in the 'success' group than in the 'failure' group (4 days vs 10 days; P < 0.001). Fewer immediate wound complications were sustained in the 'success' group than in the 'failure' group (1.2% vs 10.7%; P < 0.001). The total number of immediate or delayed complications and particularly the number of recurrent obstructions after hospitalization as well as the number of deaths did not differ significantly between the two groups. CONCLUSIONS: Successful laparoscopic treatment of small bowel obstruction can be expected in patients who are seen early, and who have had one or two previous interventions (particularly appendectomy, especially if bands are found).

Acute Disease↗

Biokinetics of a F(ab')3 iodine-131 labeled antigen binding construct (Mab 35) directed against CEA in patients with colorectal carcinoma.

UNLABELLED: An 131I labeled trivalent antigen binding construct, formed from 3 Fab' fragments of murine anti-CEA monoclonal antibody (Mab) 35, has shown favorable biokinetics in animal studies. OBJECTIVES: The aim of this study was to evaluate biodistribution and tumor uptake of 131I-F(ab')3 in patients and its potential utility for radioimmunotherapy of CEA expressing tumors. PATIENTS AND METHODS: Six patients (5 M, 1 F; age 62 +/- 13 y) with liver metastases of colorectal cancer, scheduled for hepatic surgery were studied by 2-3 whole body scans immediately post infusion of 111-137 MBq of 131I labeled Mab 35 F(ab')3 and up to 72 h. Circulating CEA ranged from 1.2 to 1930 ng/ml. We evaluated plasma and whole body clearance, activity accumulation by post-surgical ex-vivo tissue measurement in primary tumor (T) and metastases (M), and calculated M to blood (M/B) and M to liver (M/L) ratios. RESULTS: All known tumor sites were detected by immunoscintigraphy and confirmed at surgery. Whole body effective T1/2 calculated in two patients was 51.5 h and 55.6 h respectively. Effective serum T1/2 was mono-exponential in 3 patients (short observation interval) with 20.9 +/- 7 h and bi-exponential in three with alpha T1/2 of 6.3 +/- 1 h and beta T1/2 of 38.6 +/- 5 h. In a patient with concomitant colic and hepatic lesions uptake of primary tumor was 0.0071% injected dose per gram of tissue (%ID/g) and mean metastases activity was 0.0275 %ID/g at 48 h. In the 3 patients who had surgery at 48 h, mean uptake in metastases and normal liver was 0.0182 %ID/g and 0.0021 %ID/g, respectively (M/L 8.67). In the single subject followed until 7 days post infusion, residual activity in liver metastases was 10 times higher than in normal parenchyma. CONCLUSIONS: Tumor uptake and tumor to blood ratio, as well as serum clearance of the triconstruct are similar to those observed with intact iodinated anti-CEA antibodies. In the patient studied for 7 days the tumor residence time was favorable. Further improvements, however, need to be obtained before considering this approach for radioimmunotherapy.

Adenocarcinoma↗

[Living donors in kidney and liver transplantation].

The shortage of organs available for transplantation has rekindled the interest for the kidney living donor, and has recently induced the use of living donors for liver transplantation too. Both methods raise many medical and ethical interrogations. The aim of this paper is to analyse this type of organ harvesting, and to report our experience and results with kidney and liver living donors.

Ethics, Medical↗

[Twelve years of liver transplantation in Lausanne].

From 1988 to June 2000 138 transplantations were performed in 129 adult patients. Actuarial patient and graft survivals have been 80.7% and 75.4% at one year and 67.8% and 63.5% at 10 years. This compares favourably with the statistics of the European Liver Transplant Registry that collected data from more than 30,000 grafts. Over the twelve years of activity, the indications have become more liberal and the techniques have been simplified. The waiting list has therefore grown and some patients are now unfortunately dying before a graft can be found because the number of brain dead donors remains stable. In order to palliate this shortage, older donors are now being accepted even with co-morbidities and/or moderate alterations of the liver function tests. The use of live donors and the split of the best cadaveric grafts for two recipients will also reduce the gap between the demand and the offer.

Actuarial Analysis↗

Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma.

BACKGROUND: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. METHODS: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration-time curve over 120 min. RESULTS: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 +/- 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. CONCLUSIONS: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.

Catecholamines↗