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D O'Toole

Publications and source records attributed to D O'Toole.

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↗
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

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↗
PubMed2005

Myositis, lameness, and recumbency after use of water-in-oil adjuvanted vaccines in near-term beef cattle.

A producer administered 2 US Department of Agriculture-licensed adjuvanted veterinary vaccines (inactivated bovine rotavirus-coronavirus vaccine; Clostridium perfringens type C-Escherichia coli bacterin-toxoid) into muscles of the left and right hips of 469 pregnant beef cows. Within 24 hours, 5 cattle were recumbent, and another 2 had non-weight bearing pelvic limb lameness (1.5% affected; 7/469). During the next 10 days, 50% of the herd developed firm swellings up to 24 cm in vaccination sites in muscles of the hip. Histological samples revealed granulomatous myositis with intralesional oil. Lesions resolved slowly during the next 6 months. Six cattle were injected experimentally with the vaccines. None became lame, but all developed foreign body granulomatous myositis similar to those in the affected herd. The maximum diameter of experimentally induced lesions in muscle at necropsy 60 days after injection with the recommended dose of the bacterin-toxoid vaccines was 12 cm. Histological examination revealed pyogranulomatous myositis, fibrosis, and myonecrosis. The inactivated viral vaccine induced milder granulomatous myositis with intralesional lipid and scant fibrosis. Acute transient lameness on the ranch was attributed to use of 2 irritating biological vaccines in the hip muscles of cows that were close to parturition.

Adjuvants, Immunologic↗
PubMed2005

Fatal mycobacteriosis with hepatosplenomegaly in a young dog due to Mycobacterium avium.

Cases of disseminated Mycobacterium avium infections in dogs are rare because it appears that the species is innately resistant to infection. A 2-year-old, castrated, 5 kg Shih Tzu-Poodle-cross developed anemia, abdominal pain, lethargy, and splenomegaly. Histological examination of surgically removed spleen indicated marked granulomatous splenitis with myriad intracytoplasmic acid-fast bacterial rods. Ultrastructural examination revealed the presence of 3-4-microm-long mycobacteria in phagolysosomes of epithelioid macrophages. Tissue extract of lightly fixed spleen was positive for M. avium 16S ribosomal RNA and negative for M. tuberculosis complex IS6110 DNA by polymerase chain reaction testing. Anemia was associated with the presence of mycobacteria-infected macrophages in bone marrow. The animal's condition deteriorated, and euthanasia was performed after a clinical course of 2 months. The principal morphological findings at necropsy were severe diffuse granulomatous hepatitis, enteric lymphadenomegaly, and segmental granulomatous enteritis with intralesional mycobacteria present. Mycobacterium avium was cultured from enteric lymph nodes sampled at necropsy. The source of infection was not established but was presumed to be environmental with an enteric portal of entry.

Animals↗
PubMed2005

Status spongiosus of white matter in newborn Gelbvieh-cross calves.

Various forms of status spongiosus occur in neonatal cattle, the best characterized of which is due to mutations of the branched-chain alpha-keto acid dehydrogenase complex (BCKD), resulting in bovine maple syrup urine disease (MSUD, branched-chain ketoaciduria). A distinctive neurological syndrome was identified between 1998 and 2003 in 9 calves in a 250-cow stabilized Gelbvieh-Red Angus herd. Both sexes were affected (6 heifers, 3 bulls), with a low annual incidence (3 cases in 1998; no cases in 1999; 2 cases in 2000; 2 in 2001; 1 in 2002; 1 in 2003). Affected calves were born full-term, unable to stand, and had constant whole-body tremors when stimulated. Animals remained in lateral recumbency until death or euthanasia; the longest survival time was 10 days postpartum. The principal histological change in 2 affected calves was diffuse, moderately severe bilaterally symmetrical status spongiosus with Alzheimer type II cells throughout the white matter of the brain. Myelin deficits were not evident and vacuoles were due to cleaved myelin sheaths. Neither recognized mutation of MSUD was identified in the E1a subunit of BCKD in 2 affected calves, 8 dams that gave birth to affected calves, a grand-dam of 3 affected calves, or a sire of 1 calf. Amino acid analysis of serum from 1 affected calf revealed normal concentrations of branched-chain amino acids, indicating that this disease is distinct from MSUD. The genetic and biochemical basis for the disorder, provisionally named congenital status spongiosus of Gelbvieh-cross cattle, is undetermined. The pattern of inheritance was not established.

Animals↗
PubMed2004

Abomasal emptying defect of sheep may be an acquired form of dysautonomia.

Abomasal emptying defect (AED) is a disease syndrome that primarily affects Suffolk sheep and is characterized by distension and impaction of the abomasum. No histologic lesion has been consistently associated with this condition. There is no known etiology. In this study, nine cases of AED were identified by necropsy, including three rams and six ewes between 2 and 6 years of age. Four of the cases occurred sporadically, and five ewes were submitted on the same day from a single flock. Histologic examination of celiacomesenteric ganglia from six of the affected sheep revealed scattered chromatolytic or necrotic neurons, without inflammation. Chromatolytic neurons were observed more frequently in AED-affected sheep than in seven healthy Suffolk sheep (P < 0.08, weak statistical support). Neuronal necrosis was not observed in any of the healthy sheep. Lineage records of the flock that suffered an outbreak were incompatible with the possibility of a simple inheritance pattern for this disease; furthermore, the very occurrence of AED in outbreak form is inconsistent with transmission solely by inheritance. Only one of the six tested sheep showed concurrent immunohistochemical evidence of scrapie. The lesion pattern in celiacomesenteric ganglia is suggestive of a neurotoxicosis. Neuronal lesions of AED resemble dysautonomic diseases of humans and other animals.

Abomasum↗
PubMed2004

Skeletal changes in hemochromatosis of Salers cattle.

Hemochromatosis is an inherited defect in Salers cattle, characterized by increased iron absorption and wasting in young animals. Loss of teeth and soft bones has been reported. This study details bone changes in a prospective study of an affected Salers heifer and an age-matched, half-sibling control. The heifer fell 2 weeks before euthanasia, developed non-weight bearing lameness, and then became recumbent. At necropsy, the heifer was smaller than the control and had fractures of the humerus, femur, and ribs. Distinctive circumferential laminations in the outer third of the cortex were seen radiographically as layers of variably decreased density. In midshaft cross sections, the cortex was wider in some long bones, and fluorescent labeling revealed irregular and intermittent mineralization in the outer cortical layers. Mineral apposition rates in osteons of the inner cortex were decreased as compared with the control, and longitudinal bone formation at the growth plate was markedly decreased. Histologically, there were buried layers of osteopenic, poorly mineralized plexiform bone in outer circumferential lamellae. There was stainable iron in woven bone cores of the matrix. Iron was found in occasional osteoclasts as well. The mandible was severely affected, with loss of cortical bone as well as trabecular bone around the teeth and resorption of dental roots. Bone analysis revealed iron levels in the affected calf that were 30-50 times greater than the control and decreased percent ash in the outer cortex. These results indicate that periosteal dysplasia and osteopenia are responsible for pathologic fractures and tooth loss.

Animals↗
PubMed2003

Chronic hyperplastic and neoplastic cutaneous lesions (Marjolin's ulcer) in hot-brand sites in adult beef cattle.

Linear exophytic cutaneous lesions (brand keratomas) are a chronic sequel to hot-iron branding in a small proportion of beef cattle in the western United States. Rarely, brand keratomas progress to form large ulcerated masses. Samples of chronically thickened skin were collected from 8 adult cattle with hot-brand lesions and from 2 cattle with ulcerated masses at brand sites. Cutaneous thickening was attributable to abrupt transition from normal haired skin to regular epidermal hyperplasia with marked orthokeratotic hyperkeratosis, acanthosis, hypopigmentation, and loss of adnexae. Epithelial atypia was absent. Normal dermal collagen was replaced by mature granulation tissue containing islands of dense hyalinized collagen. Two cows, aged 5 and 13 years, developed large, slow-growing squamous cell carcinomas at brand sites. Malignancy in branded skin is a rare complication of hot-iron branding in cattle and may arise because of malignant transformation of brand keratomas.

Animals↗
PubMed2003

Papular dermatitis induced in guinea pigs by the biting midge Culicoides sonorensis (Diptera: Ceratopogonidae).

Histological, ultrastructural, and virological examinations were performed on abdominal skin from guinea pigs after a blood meal by colony-bred biting midges, Culicoides sonorensis. Small, superficial, cutaneous, crateriform ulcers with necrosis of superficial dermis developed at feeding sites and healed within 24-48 hours. Animals developed nonpruritic erythematous papules 5 days after feeding that persisted until the study ended at 12 days after feeding. Papules corresponded histologically to foci of epidermal hyperplasia and superficial interstitial dermatitis with intraepidermal micropustules and scattered intraepidermal polykaryons. The principal ultrastructural changes were spongiosis in germinal epithelium and neutrophilic-histiocytic exocytosis. No viral agents or broken mouthparts were identified in lesions. The dermatitis may represent a host reaction to persisting insect salivary secretion and should be considered as an additional consequence of blood feeding in future studies involving biting midges.

Animals↗
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

Evaluation of renal function following treatment with 5-aminosalicylic acid derivatives in patients with ulcerative colitis.

BACKGROUND: A number of cases of nephrotoxicity have been reported in patients with inflammatory bowel disease taking oral 5-aminosalicylic acid (5-ASA). AIM: To evaluate the effects of 9 months of therapy with mesalazine or olsalazine on renal function in patients with ulcerative colitis in remission. METHODS: Forty patients with ulcerative colitis in complete remission for 6 months were randomized to either olsalazine (n=20) or mesalazine (n=20 for nine months). Thirty-six of the 40 patients were on prior salicylate therapy. Disease activity was the measure ofclinical efficacy and was assessed by the Harvey-Bradshaw Index (HBI). Laboratory efficacy measurements included glomerular filtration rate (GFR), microalbuminuria, urinary gluthathione S-transferase (GST) and serum C-reactive protein (CRP). Safety analysis consisted of documentation of adverse events and laboratory values. RESULTS: There was no significant reduction in the GFR overall on therapy. The levels of GFR adjusted for baseline were similar in the two treatment groups after 3, 6 and 9 months. A significantly higher percentage of mesalazine-treated patients experienced drug related adverse events, all of a minor nature. The incidence of adverse events causing early withdrawal was similar in the two treatment groups. CONCLUSION: Treatment with mesalazine or olsalazine for 9 months had no significant impact on GFR.

Adult↗
PubMed2002

Intraductal papillary and mucinous pancreatic tumour: a new extracolonic tumour in familial adenomatous polyposis.

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.

Adenocarcinoma, Mucinous↗
PubMed2002

Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma.

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.

Adenocarcinoma, Mucinous↗