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P Ruszniewski

Publications and source records attributed to P Ruszniewski.

At least 19 recordsLinked to original sources
PubMed2006

Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours.

Transcatheter arterial chemoembolisation (TACE) has been reported to be an efficient treatment of liver metastases of endocrine tumours in short series of patients. However, several factors seem to affect its results. The aim of this work is to identify predictors of response to TACE for liver metastases of endocrine tumours. A total of 163 TACE procedures were performed in 67 patients between 1994 and 2004. Forty-four patients were treated with streptozotocin and 23 with doxorubicin. Primary tumour was located in the pancreas for 19 patients, and had been removed in 43. Thirty-eight tumours were functioning. Response rate was 37% (confidence interval [CI] 95%: 28-49%). Median time to progression (TTP) was 14.5 months (CI 95%: 9-41). In multivariate analysis (n=43), predictors of tumour response were body mass index (BMI) (odds ratio [OR]: 1.3; CI 95%: 1.04-1.63; P=0.022), functioning type of tumour (OR: 7.31; CI 95%: 1.26-42.5; P=0.027), arterial phase enhancement on abdominal computed tomography (CT) (OR: 8.11; CI 95%:1.06-62; P=0.044) and use of streptozotocin for cytotoxic agent (OR: 21.3; CI 95%: 1.48-306; P=0.025). Analysis of TTP predictors showed that BMI (hazard ratio [HR]: 0.85; CI 95%: 0.76-0.86; P=0.01) and arterial phase enhancement (HR: 0.3; CI 95%: 0.12-0.73; P=0.008) were associated with delayed progression. This large study confirms the previously reported results of TACE regarding its efficacy for the treatment of liver metastases of endocrine tumours. Arterial phase enhancement on abdominal CT and BMI are predictors of treatment's efficacy. Streptozotocin should be the preferred cytotoxic agent in order to save anthracycline for systemic chemotherapy.

Adult↗
PubMed2006

A new large CFTR rearrangement illustrates the importance of searching for complex alleles.

The p.Val754Met variant, described in 1996 in a CF patient, has been considered a CF mutation. However, biochemical aspects, results of functional studies and, finally, the identification of a complex deletion removing exons 3 to 10 and 14b to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious effect. An inventory through the French CF network of patients carrying p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the variation. Extensive CFTR gene analysis was carried out, including the search for large rearrangements and other possible mutations. The complex deletion, whose breakpoints are described here, was found only in the four CF patients, in association with the same haplotype. This data, added to the fact that the p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring further arguments against the association of p.Val754Met with CF. We thus suggest looking for a possible complex allele whenever p.Val754Met is detected and considering it neutral regarding genetic counseling when found in isolation.

Adolescent↗
PubMed2006

Human pancreatic mucinous cystadenoma is characterized by distinct mucin, cytokeratin and CD10 expression compared with intraductal papillary-mucinous adenoma.

AIMS: To examine cytokeratin, epithelial glycoprotein (mucin) and glycoprotein CD10 expression in benign mucinous cystdenomas (MCAs) in comparison with intraductal papillary mucinous adenomas (IPMAs). METHODS AND RESULTS: Thirty MCAs of the pancreas were analysed for immunohistochemical expression of cytokeratin (CK) 7, CK20, MUC1, MUC2, MUC5AC and CD10 and were compared with 16 IPMAs. CK7 was expressed in all neoplasms. CK20 was significantly more frequent in MCAs compared with IPMAs (56.66% versus 18.75%, P = 0.027). MUC1 was more frequent in MCAs (40% versus 12.5%, P = 0.0915), whereas MUC5AC was significantly less frequent in MCAs (33.33% versus 100%). MUC2 was expressed in goblet cells of seven MCAs. In MCAs, CD10 was observed both in epithelial cells and in the ovarian-type stromal cells (24/30). Epithelial expression of CD10 was significantly lower in IPMAs (66.66% versus 6.25%, p = 0.0001). CONCLUSIONS: MCA is characterized by a significantly greater frequency of expression of CK20 and CD10 when compared with IPMA, which preferentially expresses MUC5AC.

Adolescent↗
PubMed2005

Endocrine pancreatic tumours and helical CT: contrast enhancement is correlated with microvascular density, histoprognostic factors and survival.

PURPOSE: To assess the role of contrast-enhanced helical CT in the evaluation of tumour vascularity in endocrine pancreatic tumours (EPTs), and to determine the predictive factors of malignancy of EPTs at helical CT with CT-histopathological correlation. MATERIALS AND METHODS: Thirty-seven consecutive patients with histopathologically proven EPTs underwent dual-phase helical CT. For each tumour detected, its density relative to the surrounding parenchyma was scored on the pancreatic phase using a 5-point scale. Radiological findings were correlated with histopathological (vessel density count) and clinical follow-up findings. RESULTS: Thirty of 37 patients had non-functioning EPTs and overall 44 tumours were detected by helical CT (mean size 38, range 5-100 mm). CT showed calcifications in 10 tumours. Calcifications were associated with well-differentiated carcinomas (90%, p = 0.02). Vascular density assessed by light microscopy was significantly correlated with tumour enhancement at the pancreatic phase (p = 0.0001). Poorly differentiated carcinomas were less vascularised than well-differentiated tumours and carcinomas (34 vs. 264 vessels/mm2, p = 0.0073). Tumour differentiation also correlated with tumour enhancement at the pancreatic phase (p = 0.0044, trend test): poorly differentiated carcinomas were hypoattenuating (71%) and isoattenuating or weakly hyperattenuating (29%), compared with well-differentiated carcinomas and tumours that were mainly moderately or strongly hyperattenuating (53%). In univariate analysis, poor tumoral differentiation, hepatic metastasis, high mitotic index, poor tumoral enhancement at the pancreatic phase and less vascularised tumours were correlated with decreased survival rate. CONCLUSION: Enhancement of EPT at CT is correlated with tumour vascularity assessed by light microscopy. Low-enhancing EPT at CT are correlated with poorly differentiated EPT and with a decrease in overall survival.

Adult↗
PubMed2005

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression.

Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series of patients with pancreatic endocrine tumours (PETs). The expression of vascular endothelial growth factor (VEGF), HIF-1alpha, HIF-2alpha and carbonic anhydrase 9 (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density (MVD), endothelial proliferation, tumour stage and survival. Microvascular density was very high in PETs and associated with a low endothelial index of proliferation. Microvascular density was significantly higher in benign PETs than in PETs of uncertain prognosis, well-differentiated and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels mm(-2), respectively, P < 0.0001). Well-differentiated tumours had high cytoplasmic VEGF and HIF-1alpha expression. Poorly differentiated carcinomas were associated with nuclear HIF-1alpha and membranous CA9 expression. Low MVD (P = 0.0001) and membranous CA9 expression (P = 0.0004) were associated with a poorer survival. Contrary to other types of cancer, PETs are highly vascularised, but poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD significantly decreases. The regulation of HIF signalling appears to be specific in pancreatic endocrine tumours.

Adenoma, Islet Cell↗
PubMed2005

Primary endocrine tumours of the liver.

BACKGROUND: In patients with hepatic endocrine tumours, a primary neoplasm is not always found elsewhere despite extensive investigations, raising the possibility that the hepatic lesion is the primary tumour. The aim of this study was to assess the incidence, characteristics and prognosis of patients with primary hepatic endocrine tumours. METHODS: Patients with histologically confirmed hepatic endocrine tumours identified since 1993 were reviewed. All those with no primary tumour identified by computed tomography of the thorax, abdomen and pelvis, upper and lower digestive endoscopy, duodenopancreatic endoscopic ultrasonography or somatostatin receptor scintigraphy (SRS) were included. Clinical and tumour characteristics were assessed retrospectively. RESULTS: Of 393 patients with digestive endocrine tumours, 17 (seven men; median age 55 (range 26-69) years) had hepatic endocrine tumours without evidence of an extrahepatic primary lesion either at diagnosis or during a median follow-up of 43 (range 12-108) months. Ten patients had multiple and seven had single tumours. The tumours were non-functional in 13 patients and well differentiated in 14 patients. SRS was positive in the liver in 11 patients. Curative resection was performed in seven. Overall actuarial survival rates were 100, 69 and 51 per cent at 1, 3 and 5 years respectively. Only poor differentiation was associated with an unfavourable outcome (relative risk 20.8; P < 0.001). CONCLUSION: Primary hepatic endocrine tumours were identified in almost 5 per cent of patients with digestive endocrine tumours. Poor differentiation was the only factor associated with unfavourable outcome.

Adult↗
PubMed2005

[Intraductal papillary mucinous tumours of the pancreas: imaging features].

IPMTP is a pancreatic duct disease that can better be diagnosed due to advances in imaging techniques. This probably explains the recent increased frequency of this disease. Enlargement of the main pancreatic duct and/or branch ducts is a typical feature. CT and MRI with MRCP are useful for diagnosis. Features of malignant degeneration are better known. Preoperative staging is performed at CT. Differential diagnosis includes main pancreatic duct dilatation and pancreatic cysts. Recent papers indicate that isolated side branch IPMTP is less frequently malignant. Surgery is indicated in the presence of acute pancreatitis or suspicion of malignant degeneration. Imaging is useful for the follow up of patients with isolated side branch IPMTP. In this paper, the diagnostic, staging and malignant features of IPMTP will be reviewed.

Carcinoma, Pancreatic Ductal↗
PubMed2005

Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.

AIMS: To study the expression of hypoxia-regulated markers in pancreatic ductal adenocarcinomas (PA) in relationship to the presence of a fibrotic focus, angiogenesis quantification and clinical outcome. METHODS AND RESULTS: The expression of hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) was immunohistochemically detected in 50 PA and correlated with tumour characteristics, microvascular density (MVD) and survival. HIF-1alpha was expressed within tumour cells in 68%, HIF-2alpha in 46%, CA9 in 78% and VEGF in 52% of the cases. Stromal expression was also noted for HIF-2alpha and CA9 in, respectively, 42% and 48% of the cases. Tumour CA9 expression was associated with that of VEGF (P=0.004) and that of stromal HIF-2alpha (P=0.013), with the presence of a fibrotic focus (P=0.046) and with an increased MVD (P=0.034). Tumour VEGF expression correlated with the presence of a fibrotic focus (P=0.039) and a greater MVD (P=0.047). Both the presence of a fibrotic focus (P=0.0002) and high tumour CA9 expression (P=0.029) were associated with reduced overall survival. CONCLUSION: The strong association of the presence of a fibrotic focus with CA9 expression and lower survival demonstrates that hypoxia-driven angiogenesis plays an important role in the progression of PA.

Adult↗
PubMed2004

[Gastrinomas in multiple endocrine neoplasia type-1. A 127-case cohort study from the endocrine tumor group (ETG)].

UNLABELLED: On July 2000, 127 gastrinomas (31.1%) were studied by the Endocrine Tumour Group (GTE) using a 408-patient cohort of Multiple Endocrine Neoplasia Type 1 patients. The aim of this study was to assess clinical, biological, surgical data as well as their trends over three periods (<1980-1980/1989->1990). A Zollinger-Ellison syndrome (SZE) was present in 96% of the cases. Mean age at the onset of the disease was 39.4 years. There were 55.9% of men. Synchronous liver metastasis was present in 7.1%. Taken independently, the positivity of the four main diagnosis tests decreased over the time. The diagnosis of oesophagitis increased (4.5-29.7%), as well as the size of the resected tumours (9.9-16.8 mm). There was an increase in the familial background diagnosis (73.1-80%), an increasing use of Octreoscan scintigraphy and transduodenal ultrasound with positive detection of metastasis and tumours in 81.3% and 92.3%, respectively after 1991. Patients were operated on less frequently (96-52.5%), less frequently from the pancreas (87.5-37.5%), and from the gastro-intestinal tract (70.8-30%). The relative percentage of major pancreatic resections increased (with at least removal of the duodenum and the pancreatic head) (10-26.7%). The operative mortality disappeared. Six out of the seven patients (85.7%) who benefited from major pancreatic resections normalized their gastrine level postoperatively versus 15% in less radical techniques. Overall 5 years survival was 90 +/- 4.4%. Survival increased after 1985 (85 +/- 4.8% versus 95 +/- 3.6, P = 0.1). CONCLUSION: SZE in NEM1 were diagnosed at an earlier stage and were less frequently operated on. Nevertheless, the incidence of synchronous metastasis did not change significantly. Patients were mainly operated on for gastric emergencies and pancreatic tumours in order to prevent metastasis without mortality after 1991.

Adult↗
PubMed2004

The burden cost of French patients suffering from irritable bowel syndrome.

BACKGROUND: The impact of irritable bowel syndrome (IBS) on health-care resource use in France is evaluated, and explanatory variables determined. METHODS: A questionnaire comprising socio-demographic characteristics, symptoms, consumption of resources, quality of life and impact of IBS on productivity was administered by telephone to a sample of 253 French adults with IBS recruited from the general population, and diagnosed with IBS using several well-known diagnostic criteria. The medical costs were estimated on a monthly basis and included medication(s), physicians' consultations, investigations and hospitalizations. RESULTS: Mean age was 48.3 years and 75% of subjects were women (192). Thirty-six percent of subjects had suffered from IBS for more than 10 years; 77% had consulted a general practitioner and 43% a gastroenterologist. Twenty-nine percent of subjects had undergone an investigation and 25% reported hospitalization; 61% of patients reported that they were taking medication. The average monthly medical costs was 71.8 euros (95% CI = [57.6-86.0]) with an asymmetric distribution (median = 28.1 euros) because of a high proportion of subjects (27%) who reported receiving no care at all. The two principal cost components were investigations (39%), and hospitalizations (22%). The highest medical costs were associated with subjects who were very elderly or suffered from severe symptoms (very severe pain), and were correlated with the lowest quality of life scores. CONCLUSION: IBS has a major impact on resource consumption and the productivity of patients. Determination of the variables to explain medical costs showed that advanced age, severe pain and deterioration in quality of life could be predictive of high medical costs.

Absenteeism↗
PubMed2004

Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system.

This consensus report gives a detailed description of the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system. As background information we have outlined critical aspects of the pathology, the use of tumor markers, a definition of functional and non-functional digestive neuroendocrine tumors, different imaging modalities, surgical considerations, liver embolization and the use of cytotoxic drugs as well as interferon. Included in the report is an overview of somatostatin, somatostatin analogs and its receptor expression in different neuroendocrine tumors. It will also define the binding affinities of different somatostatin analogs to the five different subtypes of somatostatin receptor. We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment.

Antineoplastic Agents, Hormonal↗
PubMed2003

Ablative therapies for liver metastases of digestive endocrine tumours.

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.

Catheter Ablation↗
PubMed2002

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA.

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.

Adenocarcinoma↗