The diagnostic dilemmas in discrimination between pancreatic carcinoma and chronic pancreatitis.
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Biomedical subjects
Publications and source records attributed to F Maire.
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Hepatic metastases are frequently encountered in patients with digestive endocrine tumors and their presence plays an important role in quality of life and overall prognosis. Surgery is the treatment method of choice for hepatic metastases but this is frequently impossible due to the extent of disease. Systemic chemotherapy is offered to patients with diffuse and/or progressive liver metastases but results are disappointing especially in patients with metastases of midgut origin. In the latter patients with carcinoid syndrome, somatostatin analogs are frequently initially effective but their efficacy wanes due to disease progression and development of tachyphylaxis. Other therapeutic options in the treatment of hepatic metastases are locoregional strategies where vascular occlusion induces ischemia in these highly vascular tumors using either surgical or radiological techniques. Available methods include surgical ligation of the hepatic artery, transient hepatic ischemia or sequential hepatic arterialization. Trans-catheter arterial chemoembolization has proven effective in terms of long palliation and objective tumor responses. Other treatments aimed at regional destruction either alone or in combination with surgery include radiofrequency ablation and cryotherapy. The latter are usually important adjuncts to surgery and are usually reserved for limited disease.
KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribonucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P<0.002). None of the latter developed a pancreatic cancer within the 36 months of median follow-up. The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.
Familial adenomatous polyposis (FAP) is characterised by the development of numerous colorectal adenomatous polyps. Other extracolonic benign or malignant lesions have been reported previously in association with FAP but precancerous lesions in the pancreas have never been described. We report the first case of intraductal papillary and mucinous pancreatic tumour (IPMT) in a patient with FAP. A 48 year old man with a well documented past history of FAP was admitted for epigastric pain, weight loss, and new onset diabetes mellitus. Spiral computed tomography scan revealed a large tumour in the pancreatic head with upstream main pancreatic duct dilatation. Endoscopic ultrasonography confirmed these data. Mucous secretion was seen at duodenoscopy and a lesion in the main pancreatic duct was confirmed by retrograde pancreatography. The patient underwent a pancreaticoduodenectomy for suspected IPMT. Histological examination of the resected specimen confirmed an IPMT with in situ carcinoma. Twelve months after resection, the patient remained free of tumour relapse. Genetic analysis showed loss of the wild allele of the adenomatous polyposis coli gene in IPMT, causing inactivation of both alleles and demonstrating that IPMT was not incidental in this patient. IPMT should be included in the extracolonic localisation of FAP.
BACKGROUND: Although the prognosis in malignant resectable intraductal papillary mucinous tumours of the pancreas (IPMT) is often considered more favourable than for ordinary pancreatic ductal adenocarcinoma, the long term outcome remains ill defined. AIMS: To assess prognostic factors in patients with malignant IPMT after surgical resection, and to compare long term survival rates with those of patients surgically treated for ductal adenocarcinoma. METHODS: Seventy three patients underwent surgery for malignant IPMT in four French centres. Clinical, biochemical, and pathological features and follow up after resection were recorded. Patients with invasive malignant IPMT were matched with patients with pancreatic ductal adenocarcinoma, according to age and TNM stages; survival rates after resection were compared. RESULTS: Surgical treatment for IPMT were pancreaticoduodenectomy (n=46), distal (n=14), total (n=11), or segmentary (n=2) pancreatectomy. The operative mortality rate was 4%. IPMT corresponded to in situ (n=22) or invasive carcinoma (n=51). In the latter group, 17 had lymph node metastases. Overall median survival was 47 months. Five year survival rates in patients with in situ and invasive carcinoma were 88% and 36%, respectively. On univariate analysis, abdominal pain, preoperative high serum carbohydrate antigen 19.9 concentrations, caudal localisation, invasive carcinoma, lymph node metastases, peripancreatic extension, and malignant relapse were associated with a fatal outcome. Using multivariate analysis, lymph node metastases were the only prognostic factor (OR 7.5; 95% CI: 3.4 to 16.4). Overall five year survival rate was higher in patients with malignant invasive IPMT compared with those with pancreatic ductal carcinoma (36 v 21%, p=0.03), but was similar in the subset of stage II/III tumours. CONCLUSIONS: The prognosis of patients with resected in situ/invasive stage I malignant IPMT is excellent. In contrast, prognosis of locally advanced forms is as poor as in patients with pancreatic ductal adenocarcinoma.
BACKGROUND: The risk of pancreatic cancer in patients with chronic pancreatitis (CP) is difficult to assess. Previous studies, mostly case control studies or studies relying on data case registers, reported relative risks varying from 2.3 to 18.5. METHODS: We studied a prospective, single centre, medical-surgical cohort of 373 consecutive patients (322 (86%) men, median age 40 years) with proven CP (alcoholic origin 85%) and a follow up of at least two years (median follow up 9.2 years; range 2.0-34.8) in order to exclude pancreatitis revealing pancreatic cancer. We calculated the age and sex standardised incidence ratio (SIR) as the ratio of the number of observed cases of pancreatic cancer in this cohort to the number of expected cases, as provided by the French National Cancer Register. RESULTS: Four cases of pancreatic adenocarcinoma (1.1% of patients) were observed in 3437 patient years (expected number of cases 0.15; SIR 26.7, 95% confidence interval (CI) 7.3-68.3; p=0.00002). In a second analysis in which patients lost to follow up were considered to be followed up until the end point without having developed pancreatic adenocarcinoma (4762 patient years), SIR was 19.0 (CI 5.2-48.8; p=0.00007). CONCLUSION: Patients with CP have a markedly increased risk of pancreatic cancer compared with the general population.
Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and antifungals, local GM-CSF, Glutamide, Low-energy laser, corticosteroïds). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or antifungal topicals (bicarbonates, Amphotéricine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal-sparing block, conformal radiotherapy and intensity-modulated radiation therapy).
PURPOSE: To evaluate the efficacy of postoperative brachytherapy alone (brachy) for Stage T1-2 squamous cell carcinomas (SCC) of the floor of mouth (FM) and the oral tongue (OT) with close or positive margins. METHODS AND MATERIALS: Between 1979 and 1993, 36 patients with T1-2 N0 (24 T1, 12 T2) OT (19), and FOM (17) SCC with close or positive margins following surgery underwent postoperative brachy. Mean patient age was 56 years (range 37-81) and sex ratio was 3.5:1 male:female. Mean surgery to brachy interval was 36 days (range 16-68). The technique used was interstitial Iridium-192 ((192)Ir) brachytherapy with plastic tubes and manual afterloading. Mean total dose was 60 Gy (range 50-67.4) at a mean dose rate of 0.64 Gy/h (range 0.32-0.94). Mean patient follow-up was 80 months. RESULTS: The 5-year actuarial overall and cause-specific survivals of the entire group were 75% and 85%, respectively. The local control was 88.5% at 2 years, with a plateau apparent after 23 months. Of the 4 local relapses, 2 were salvaged with surgery and external beam radiotherapy (EBR). No tumor or treatment factors, including tumor size, margin status, disease site, or radiation dose, were correlated with local control. The 2 head and neck second primaries underwent curative treatment on nonirradiated tissue. One patient developed a grade 3 sequelae (bone and soft tissue necrosis). Grade 2-3 chronic sequelae were seen in 7 of 17 and 3 of 19 FOM and OT tumors, respectively (p = 0.09). CONCLUSION: Postoperative brachy is a promising approach in T1-2 N0 OT and FOM SCC with close or positive margins. This approach is associated with high rate of locoregional control and low risk of chronic sequelae, obviates major surgery, avoids potential sequelae of EBR (xerostomia, dysgueusia, fibrosis), and avoids treatment of second head and neck primary on nonirradiated tissues.
Surgical resection is often required for maxillary cancer, producing a communication between the oral cavity and the nose or paranasal sinuses. After maxillectomy, patients experience major dysfunction in speech and swallowing which have a very negative psychological effect. These problems can be overcome with an immediate prosthesis but to be fully successful, coordinated work is required between the surgeon and the maxillofacial prosthodontist before, during and after surgery. Ten days after surgery, an interim obturator is made with soft lining materials. This prosthesis will evolve as scar tissue forms, preparing space for the definitive obturator which will restore good quality of life for maxillectomy patients.
The core problem of rule-extraction from feed-forward networks is an inversion problem. In this article, we solve this inversion problem by backpropagating unions of polyhedra. We obtain as a by-product a new rule-extraction technique for which the fidelity of the extracted rules can be made arbitrarily high.
UNLABELLED: The value of procalcitonin (PCT) measurement is not presently completely assessed for the diagnosis of neonatal infections. PATIENTS AND METHODS: This parameter was assessed in a prospective study in the neonatal intensive care unit of Clermont-Ferrand Hospital (France) in comparison to C-reactive protein. All newborn infants admitted before 24 h of life (day 0) in the neonatal intensive care unit were included in the study. Newborns (102) were assigned to one of four groups: group 1: non-infected newborns (n = 41); group 2: possibly infected newborns (n = 33); group 3: probably infected newborns (n = 10); group 4: confirmed infections (n = 18 bacterial or fungal infections). C-reactive protein and PCT were determined in the sera at D0, D1, D3 and D8. We determined the optimal cutoff value of PCT using the Receiver Operating Characteristic curves (R.O.C.). RESULTS: The cutoff value is 1.5 ng/mL at D0 and 10 ng/mL at D1. PCT cutoff value is significantly higher at D1 because of a significant PCT peak on the first day of life independent of any infectious stimulus. Our study shows that at D0 and D1 infected newborn infants had significantly higher mean PCT and C-reactive protein values than non infected newborn infants. C-reactive protein has a better specificity but PCT has better sensitivity and negative predictive value. CONCLUSION: PCT seems to be an interesting marker of neonatal infections especially during the first 24 h of life even though the mechanism of PCT synthesis remains unclear.
Dieulafoy's disease is an unusual cause of gastrointestinal hemorrhage, reported to account for less than 2% of acute gastrointestinal bleeding episodes. Bleeding occurs from a defect in an unusually large submucosal artery, through a minute mucosal erosion. Endoscopic diagnosis is sometimes difficult, but primary endoscopic therapy may be successful and should be attempted. In most cases the lesion is found in the proximal stomach. Sixteen cases of Dieulafoy's lesion located in the colon have been reported in the literature but only nine have been confirmed by histology. We present the case of a 63 year-old male with Dieulafoy's lesion of the transverse colon which was diagnosed by endoscopy and confirmed by histology.
Defects in host defences may provide a partial explanation for the increased incidence of infection in individuals with Down syndrome. Neutrophil and monocyte cellular and humoral chemotaxis were evaluated to explore phagocytic function. Fourteen individuals with Down syndrome and fifteen matched institutionalised controls were studied. In addition, a non-matched comparison normal group was investigated, representing a non-institutionalised young adult population. Neutrophil chemotaxis in institutionalised individuals (both Down syndrome and matched controls) was significantly impaired. Monocyte chemotaxis in this group was lower than in comparison normals. Evaluation of humoral components of neutrophil chemotaxis revealed no significant differences between individuals with Down syndrome and those with no known chromosomal abnormality. Down syndrome subjects had diminished humoral monocyte chemotactic responses compared with institutionalised controls and normal subjects.
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In 2103 women with vulvo-vaginal candidiasis proved by culture, econazole (an antimycotic drug, also effective against gram-positive bacteria) was administered as vaginal cream (1077 patients) or in ovules (1026 patients). The cure rate for each method was about 90% one week after the end of treatment. Although each of the methods of administration contained the same amount of effective substance, the cure rate four weeks after end of treatment was higher for the ovules (90.3%) than the vaginal cream (86.5%).