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P Callard

Publications and source records attributed to P Callard.

At least 19 recordsLinked to original sources
PubMed2006

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling.

We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

Adenocarcinoma↗
PubMed2006

[Hepatic steatosis: an emerging cause of cirrhosis in HIV patients].

Hepatic steatosis is an emerging cause of morbidity in antiretroviral therapy (ART)-experienced HIV patients. The influence of steatosis on fibrosis is poorly understood. We report two cases of rapid evolution of disseminated macrovacuolar steatofibrosis to cirrhosis. Both patients had no history of alcohol abuse, nor intravenous drug use and were tested negative for HCV (PCR RNA) and had no HBS antigen. Patient 1 had a past history of hypertrygliceridemia, but controlled with dietetic measures for 4 years prior to biopsy. The first hepatic biopsy showed a disseminated macrovacuolar steatosis (>80%). The patient had then cytolysis and an uncontrolled HIV viral load. The second biopsy was performed two years later, and HIV was controlled by a new line of ART. It showed a regression of the steatosis (10%) and a progression of the fibrosis with signs of cirrhosis. Patient 2 had a long history of HIV infection. He also had an uncontrolled dyslipidemia. The first biopsy was realised during a period of uncontrolled HIV infection and elevated liver enzymes. The biopsy showed a major macrovacuolar steatosis (>80%). The second biopsy was realised 6 years after and showed the same steatosis and signs of cirrhosis. The HIV infection was then under control. Observations reported here show a rapid evolution of liver steatosis to cirrhosis in HIV positive / HCV negative patients, despite the control of HIV infection. The implication of HAART remains unclear. In the era of HAART, liver steatosis can rapidly evoluate to cirrhosis without any risk factor except ART.

Adult↗
PubMed2006

Detection of occult carcinomatous diffusion in lymph nodes from head and neck squamous cell carcinoma using real-time RT-PCR detection of cytokeratin 19 mRNA.

The aim of the present study was to evaluate the occult lymph node carcinomatous diffusion in head and neck squamous cell carcinoma (HNSCC). A total of 1328 lymph nodes from 31 patients treated between 2004 and 2005 were prospectively evaluated by routine haematoxylin-eosin-safran (HES) staining, immunohistochemistry (IHC) and real-time Taqman reverse-transcriptase polymerase chain reaction (real-time RT-PCR) assay. Amplification of cytokeratin 19 (CK19) mRNA transcripts using real-time RT-PCR was used to quantify cervical micrometastatic burden. The cervical lymph node metastatic rates determined by routine HES staining and real-time RT-PCR assay were 16.3 and 36.0%, respectively (P<0.0001). A potential change in the nodal status was observed in 13 (42.0%) of the 31 patients and an atypical pattern of lymphatic spread was identified in four patients (12.9%). Moreover, CK19 mRNA expression values in histologically positive lymph nodes were significantly higher than those observed in histologically negative lymph nodes (P<0.0001). These results indicate that real-time RT-PCR assay for the detection of CK19 mRNA is a sensitive and reliable method for the detection of carcinomatous cells in lymph nodes. This type of method could be used to reassess lymph node status according to occult lymphatic spread in patients with HNSCC.

Adult↗
PubMed2004

Treatment of anterior vaginal wall prolapse with porcine skin collagen implant by the transobturator route: preliminary results.

OBJECTIVE: To assess the feasibility and efficacy of porcine skin collagen (Pelvicol) implant by the transobturator route for the treatment of anterior vaginal wall prolapse. PATIENTS AND METHODS: Twenty-seven women with stage III or IV prolapse underwent anterior vaginal wall repair with porcine skin collagen implantation by the transobturator route, together with bilateral sacropinofixation; respectively 17 and 16 women underwent hysterectomy and bilateral sapingo-oophorectomy during the same procedure. The feasibility and peri/postoperative complications of the transobturator procedure were assessed, together with anatomical and functional outcome. RESULTS: Porcine skin collagen implantation was feasible in every case. The transobturator procedure lasted a median of 25 min (range 20-35). There were no vessel or bladder injuries and no postoperative complications (including infections). Median follow-up was 14 months (range 8 to 24). No rejection of the porcine grafts occurred. Twenty-two women (81%) had optimal anatomic results, while the remaining five women (19%) had persistent asymptomatic stage I or II anterior vaginal wall prolapse (1 and 4 cases, respectively). In one case the collagen implant had to be removed after one year because of persistent pain due to transfixing vaginal stitch. One patient with optimal anatomic results had recurrent stage III Ba prolapse at 18 months. Quality of life and urinary discomfort scores improved significantly after the procedure (p<0.0001 and p<0.005, respectively). CONCLUSION: These preliminary results suggest that porcine skin collagen implantation by the transobturator route is a safe and effective treatment for anterior vaginal wall prolapse.

Aged↗
PubMed2004

Histopathological validation of the sentinel node concept in cervical cancer.

BACKGROUND: The sentinel node (SN) is defined as the first node in the lymphatic system that drains a tumor site. If the SN is not metastatic, then all other nodes should also be disease-free. We used serial sections and immunohistochemical (IHC) staining to examine both sentinel and non-sentinel nodes (non-SNs). MATERIALS AND METHODS: From July 2001 to March 2003, 18 patients (median age, 48 years) with cervical cancer (stage IA2, one patient; stage IB1, nine patients; stage IB2, three patients; stage IIA, three patients; and stage IIB, two patients) underwent a laparoscopic SN procedure based on a combined detection method, followed by complete laparoscopic pelvic lymphadenectomy. If the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC staining, all non-SNs were also examined by the combined staining method. RESULTS: A mean of 2.4 SNs (range 1-5) and 8 non-SNs (range 4-14) were excised per patient. Eight SNs (18.2%) from five patients (27.8%) were found to be metastatic at the final histological assessment, including two macrometastatic SNs, three micrometastatic SNs and isolated tumor cells in three SNs. In 13 patients, no metastatic SN involvement was detected by H&E and IHC staining. In these 13 patients, 106 non-SNs were examined by serial sectioning and IHC, and none was found to be metastatic. CONCLUSIONS: The SN procedure appears to reliably predict the metastatic status of the regional lymphatic basin in patients with cervical cancer.

Adenocarcinoma↗
PubMed2003

[Sentinel lymph node procedure in uterine cancers: review of the literature].

In cancer research, regional lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy warranting the lymphadenectomy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of various cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and recently in breast cancer. In cervical and endometrial cancers, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results and clinical implications of sentinel node procedure in cervical and endometrial cancers.

Endometrial Neoplasms↗
PubMed2001

Worsening of hepatic dysfunction as a consequence of repeated hydroxyethylstarch infusions.

BACKGROUND/AIMS: Due to its apparent safety and low cost, hydroxyethylstarch (HES) is increasingly used as a volume expander. The aim of this retrospective study was to highlight the risk of hepatic dysfunction after iterative HES infusions. METHODS: Between April 1996 and April 1998, nine patients were referred for worsening of their clinical condition after repeated HES infusions. Six patients had previous chronic liver disease, cirrhosis in four cases. All patients underwent a liver biopsy. RESULTS: All post-HES liver biopsies showed diffuse microvacuolization of Kupffer cells, which was associated with focal hepatocyte vacuolization in seven cases. The vacuoles contained periodic acid Schiff positive material at their margins and were lysosomal by electron microscopy. The clinical symptoms of hepatic disease, although difficult to interpret in cirrhotic patients, worsened after HES infusions. Portal hypertension was noted in three non-cirrhotic patients. Serum alkaline phosphatase and gammaglutamyl transferase activities were increased when compared with previous values. Eight patients died, six of them within 1-4 weeks of hepatic failure or septic shock. In the only living patient, symptoms improved after HES withdrawal. CONCLUSIONS: Repeated administration of HES could favour severe portal hypertension, liver failure and sepsis, particularly in the setting of chronic liver disease. The basis of these adverse effects is the lysosomal storage of HES in Kupffer cells and hepatocytes.

Aged↗
PubMed2001

Induction of urokinase receptor expression in nephrotoxic nephritis.

The urokinase receptor (uPAR) is a multifunctional molecule involved in pericellular, fibrinolytic, and proteolytic activities, as well as in cell adhesion and chemotaxis and may play a role in the pathogenesis of tissue remodeling occurring during glomerulonephritis. We analyzed sequentially the expression of uPAR by immunohistochemistry and in situ hybridization in an accelerated model of nephrotoxic nephritis in rats. A strong induction of uPAR mRNA expression was observed in glomeruli as soon as 1 h after nephrotoxic serum injection. The intensity of glomerular uPAR mRNA and antigen expression increased and peaked at 24 h. At that time, numerous glomerular fibrin deposits, monocyte/marcrophage infiltration, and heavy proteinuria were observed. Fibrin deposition was detected at 6 h, peaked at 24 h, and progressively declined over the next 3 weeks, while uPAR antigen expression remained elevated until the end of the study (3 weeks). By double labeling, we showed that the expression of uPAR was mediated by both intrinsic glomerular cells and infiltrating macrophages. Severe podocytic lesions developed within 3 days after antiserum injection, and glomerulosclerosis rapidly progressed within 2-3 weeks. These results show that glomerular uPAR expression is induced in nephrotoxic nephritis and suggest that uPAR may promote local proteolysis and also tissue remodeling, leading to the late development of glomerulosclerosis.

Animals↗
PubMed2001

[Gastric epithelioid angiosarcoma, a biopsy diagnostic pitfall].

We report the case of a 70-year-old man who presented a bulky gastric mass. The diagnosis of poorly differenciated adenocarcinoma was made on the biopsy. On surgical specimen, the final diagnosis of gastric angiosarcoma with secondary intestinal involvement was established. The patient did not respond to chemotherapy and died 8 months later. The diagnosis was difficult because of epithelioid areas which expressed both cytokeratin and vascular antigens. Human herpesvirus 8 previously detected in some soft tissue angiosarcoma was not found by polymerase chain reaction.

Aged↗
PubMed2000

Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning.

PURPOSE: One of the most difficult steps of the three-dimensional conformal radiotherapy (3DCRT) is to define the clinical target volume (CTV) according to the degree of local microscopic extension (ME). In this study, we tried to quantify this ME in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Seventy NSCLC surgical resection specimens for which the border between tumor and adjacent lung parenchyma were examined on routine sections. This border was identified with the naked eye, outlined with a marker pen, and the value of the local ME outside of this border was measured with an eyepiece micrometer. The pattern of histologic spread was also determined. RESULTS: A total of 354 slides were examined, corresponding to 176 slides for adenocarcinoma (ADC) and 178 slides for squamous cell carcinoma (SCC). The mean value of ME was 2.69 mm for ADC and 1.48 mm for SCC (p = 0.01). The usual 5-mm margin covers 80% of the ME for ADC and 91% for SCC. To take into account 95% of the ME, a margin of 8 mm and 6 mm must be chosen for ADC and SCC, respectively. Aerogenous dissemination was the most frequent pattern observed for all groups, followed by lymphatic invasion for ADC and interstitial extension for SCC. CONCLUSION: The ME was different between ADC and SCC. The usual CTV margin of 5 mm appears inadequate to cover the ME for either group, and it must be increased to 8 mm and 6 mm for ADC and SCC, respectively, to cover 95% of the ME. This approach is obviously integrated into the overall 3DCRT procedure and with other margins.

Adenocarcinoma↗
PubMed2000

Glomerulosclerosis in mice transgenic for human insulin-like growth factor-binding protein-1.

BACKGROUND: The growth hormone (GH)/insulin-like growth factor (IGF) system is thought to participate in the glomerulosclerosis process. Because IGF-binding proteins (IGFBPs) modulate IGF actions and hence GH secretion, this study assessed whether mice transgenic for human IGFBP-1 have altered susceptibility to glomerulosclerosis. METHODS: A line of transgenic mice that express human IGFBP-1 mRNA in the liver under the control of the alpha1-antitrypsin promoter has been obtained, and morphological changes in the kidney tissue were assessed. Glomerulosclerosis was identified using light microscopy, light microscopic morphometry, and electron microscopy. Extracellular matrix components were analyzed by immunohistochemistry. RESULTS: There was a marked increase in mesangial extracellular matrix area in homozygous transgenic mice at three months of age as compared with heterozygous transgenic mice and nontransgenic littermates. These changes were not associated with alterations in glomerular volume or cellularity. The expansion of extracellular matrix area was related to a marked increase in laminin and type IV collagen and to the appearance of type I collagen. CONCLUSIONS: These observations indicate that the enhanced expression of IGFBP-1 may result in the development of glomerulosclerosis without glomerular hypertrophy. The changes are potentially related to a decrease in IGF-I availability and/or to an IGF-I-independent role of IGFBP-1.

Animals↗
PubMed2000

Abnormal expression of glomerular basement membrane laminins in membranous glomerulonephritis.

BACKGROUND: Proteinuria associated with glomerular diseases is secondary to alterations of the charge-selective and/or size-selective properties of the glomerular basement membrane (GBM), but molecular alterations that are responsible for these functional changes are still poorly understood. Analysis of mice harbouring a null mutation in the gene encoding the beta 2 chain of laminin has suggested that the presence of abnormal laminin chains within the GBM can be responsible for proteinuria. METHODS: We have investigated whether abnormal laminin ss chains could be detected by immunohistochemistry within the GBM of patients with proteinuria and minimal change disease (five patients), focal and segmental glomerulosclerosis (five patients), or primary membranous glomerulonephritis (10 patients). Three patients with mesangiocapillary glomerulonephritis and three patients with IgA nephropathy were also studied as controls. RESULTS: We showed that the GBM of all 10 patients with membranous glomerulonephritis, but not of patients with other glomerulopathies, contained laminin beta 1, which is normally expressed only during metanephros development. The re-expression of the beta 1 chain of laminin was not associated with that of the embryonic alpha 1 chain of type IV collagen, or with the loss of expression of vimentin and synaptopodin, two markers of differentiated podocytes. CONCLUSIONS: The presence of new laminin isoforms within the GBM of patients with membranous glomerulonephritis could play a role in the occurrence of proteinuria, by modifying either the sieving properties of the GBM or the interactions between podocytes and the GBM.

Adult↗
PubMed2000

p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck.

PURPOSE: To determine whether p53 gene status predicts tumor responses to platinum- and fluorouracil-based induction chemotherapy in locoregionally advanced squamous cell carcinomas of the head and neck. PATIENTS AND METHODS: Tumor responses of 105 patients were measured at the primary tumor site. Objective response and major response were defined by a 50% and 80% reduction in tumor size, respectively. All coding parts of p53 gene were directly sequenced. p53 expression in tumor cells was determined by immunohistochemistry. Human papillomavirus infection was detected by polymerase chain reaction. Odd ratios were adjusted by stepwise logistic regression analysis. RESULTS: p53 mutations, p53 expression, and tumor stage were sufficient to explain the variation in tumor responses to chemotherapy in multivariate models. p53 mutation was the only variable to significantly predict objective response (odds ratio, 0. 23; 95% confidence interval, 0.10 to 0.57; P =.002) and was the strongest predictor of major response (odds ratio, 0.29; 95% confidence interval, 0.11 to 0.74; P =.006). p53 expression (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.98) and tumor stage (odds ratio, 0.31; 95% confidence interval, 0.10 to 0.96) also predicted major response. Specific mutations (contact mutations) accounted for much of the reduction in the risk of major response associated with overall mutations. In complementary analyses, p53 expression was weakly predictive of major response in the subgroup with wild-type p53, and p53 mutations also predicted histologic response. CONCLUSION: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

Adult↗
PubMed1999

Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients.

OBJECTIVE: To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. METHODS: A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. RESULTS: Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. CONCLUSION: This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent.

Abdominal Pain↗
PubMed1999

Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression.

The semiquantitative histopathological analysis of the liver biopsies obtained before and after 4 years of ursodeoxycholic acid (UDCA) therapy in a cohort of primary biliary cirrhosis (PBC) patients is reported. The relationships between elementary histological lesions before treatment and their progression under therapy were assessed. At baseline, two independent groups of lesions, each of which participate in the development of fibrosis, were individualized, i.e., florid bile duct lesions and ductopenia on one hand and lymphocytic piecemeal necrosis, ductular proliferation, and lobular necroinflammatory changes on the other hand. Four years of UDCA therapy were associated with a significant decrease in the prevalence of florid interlobular bile duct (ILBD) lesions, of epithelioid granuloma (P <.001) without any aggravation in the severity of bile duct paucity. Lobular inflammation and necrosis markedly improved (P <.001) whereas the degree of severity of the lymphocytic piecemeal necrosis and ductular proliferation at entry and at 4 years were similar. Worsening of fibrosis was observed in 14 patients (12 of them had a one grade progression) whereas stabilization was noted in 30 of the remaining patients. Severity of both the lymphocytic piecemeal necrosis and lobular inflammation and necrosis at entry was significantly associated with the progression of fibrosis. The results suggest that UDCA therapy influences the process leading to bile duct destruction. Patients with severe lymphocytic piecemeal necrosis and lobular inflammation may need additional therapeutic intervention because they have increased risk of fibrosis progression.

Bile Ducts↗
PubMed1999

[Glomus tumor of the extremities].

Glomus tumor is a neuro-myo-arterial benign tumor accounting for 1 to 5% of hand tumors which occurs principally in young adult females. It may be unique or multiple. Acute, focalized, pain is the main sign, the pressure of a small trigger zone induces a syncopal pain and immediate hand withdrawal. Differential diagnoses includes neurinoma, melanoma, hematoma, osteoid osteoma, fibrokeratoma, mucoid cyst, angioma, and exostosis. The diagnosis is suspected on clinical grounds, and X rays exhibits a bone erosion in one third of the cases. Magnetic resonance angiography is now the first line non invasive tool for both diagnosis and precise localization. Treatment consists in complete surgical tumor resection (J Mal Vasc 1999; 24: 364-367).

Diagnosis, Differential↗