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F Berger

Publications and source records attributed to F Berger.

At least 19 recordsLinked to original sources
PubMed2026

Multiregion profiling of genomic and transcriptional heterogeneity in head and neck squamous-cell carcinoma.

BACKGROUND: Intratumoral heterogeneity (ITH) is thought to contribute to tumour evolution and treatment resistance but its biological and clinical significance in localised head and neck squamous-cell carcinoma (HNSCC) remains incompletely understood. PATIENTS AND METHODS: In the prospective SCANDARE study, we analysed 87 patients with resectable HNSCC treated with upfront surgery. Two to five spatially distinct tumour regions per patient underwent pathological evaluation, targeted DNA sequencing, and bulk RNA sequencing. Genomic ITH (gITH) was quantified using clonal deconvolution and Shannon diversity indices, whereas transcriptional heterogeneity (tITH) was assessed using the intratumour expression distance metric. Associations between ITH, molecular features, tumour microenvironment composition, and clinical outcomes were explored using multivariable statistical models. RESULTS: Pathology-based spatial heterogeneity showed limited prognostic value. gITH was common, with 37% of tumours displaying regionally heterogeneous pathogenic variants, including spatially actionable alterations in 10% of patients. In an initial multivariable Cox model, higher gITH was associated with shorter disease-free survival. However, after Ridge-penalised modelling and bootstrap internal validation, the effect size was attenuated [corrected hazard ratio 1.42, 95% confidence interval (CI) 0.91-2.75]. The overall model retained moderate discriminative performance (optimism-corrected C-index 0.69, 95% CI 0.59-0.79). gITH was associated with tumour cellularity, reduced estimated endothelial cell infiltration, and alterations in KMT2C and PIK3CA. tITH differed according to human papillomavirus (HPV) status, with lower tITH in HPV-positive tumours, and was associated with distinct biological pathways and genomic alterations. Genomic and tITH were not correlated. CONCLUSIONS: This prospective multiregion study provides a comprehensive characterisation of genomic and tITH in localised HNSCC. Our findings highlight substantial spatial molecular diversity within primary tumours and suggest potential associations between heterogeneity, tumour biology, and clinical outcome that warrant validation in independent cohorts.

head and neck squamous-cell carcinoma (HNSCC)↗
PubMed1992

[Lymphoproliferative syndromes associated with Epstein-Barr virus in transplantation].

We report 23 cases of lymphoproliferative diseases which occurred among 2,100 patients with kidney or combined kidney+pancreas transplant. Eleven patients developed a severe diffuse disease within the first 3 months post-transplantation; immunoblastic B cells of recipient origin infiltrated the bone-marrow, transplanted organs, liver, spleen, lymph nodes, lungs, and brain; immunoglobulin abnormalities with fever, leuko-thrombocytopenia and liver dysfunction constituted the symptoms; all patients received anti-lymphocyte globulins; 9 patients were also treated with cyclosporin. Three out of 6 tumors analysed were monoclonal. Epstein-Barr virus was present in 3 lesions analysed. Treatment consisted of cessation of immunosuppressive therapy. Nine patients died with lactic acidosis. Five patients had a less severe form. Seven patients had solid tumors involving the tonsils, lungs (2), lymph nodes (2), and bladder, 8 months after transplantation. All patients received cyclosporin; 4 also received anti-lymphocyte globulins and 3 OKT3. Tumor cells were immunoblasts expressing B cells markers at a late stage of B cell differentiation; 4 tumors were monoclonal. C myc was negative. Treatment consisted of cessation of immunosuppressive therapy, antiviral agents, and monoclonal antibodies (mAb): anti-CD21 and anti-CD24 mAb therapy was followed by cure of the lymphoma in 1 patient, by transient remission in a second one and by failure in the third patient. Two patients had a recurrence of the lymphoma and received chemotherapy; 2 patients died of the lymphoma, 1 died of unrelated cause; 4 are alive, 3 of them having a good graft function.

Antigens, CD↗
PubMed1992

[Malignant endocrine tumor of the pancreas associated with high blood thyrocalcitonin levels].

A case of thyrocalcitonin-secreting endocrine tumour of the pancreas is reported. Endocrine pancreatic tumours are neoplasias evolving over a long period; most of them are multisecreting, usually with a predominant secretion responsible for clinical symptoms. In this particular case the retrospective diagnosis of a thyrocalcitonin-secreting tumour of the pancreas was made by immunocytochemical study of the pancreatectomy specimen. One year after pancreatectomy, the persistence of clinical signs and a plasma thyrocalcitonin level higher than 25,000 pg/ml led to the discovery of a liver metastasis. An immunocytochemical study of the segmental hepatectomy specimen showed a single population of thyrocalcitonin-secreting cells identical with those found in the pancreatic tumour. In this context, radioimmunological assays of peptides and immunocytochemistry seem to be the best diagnostic methods.

Aged↗
PubMed1992

Electrophysiological characterization of histamine receptor subtypes in sheep cardiac Purkinje fibers.

The histamine-receptor-subtype-mediated effects on action potentials of electrically driven and spontaneously active isolated sheep cardiac Purkinje fibers were investigated using H1- and H2-selective agonists and antagonists. In electrically stimulated Purkinje fibers, histamine (3 mumol/l) increased the action potential plateau height, decreased the action potential duration measured at a repolarization level of -60 mV and enhanced the pacemaker activity. These effects were abolished by the H2-selective antagonist cimetidine (30 mumol/l), but were not impaired by the H1-selective antagonist dimetindene (0.3 mumol/l). In spontaneously active Purkinje fibers, histamine (10 mumol/l) increased the spontaneous rate by 24%, the slope of diastolic depolarization by 45% and shortened the duration of the diastole by 32% of the respective control measurements. These effects were blocked by 30 mumol/l cimetidine, but remained unchanged in the presence of 0.3 mumol/l dimetindene. Concentration-response curves of histamine were shifted to the right by approximately 2 logarithmic units in the presence of 30 mumol/l cimetidine, but were not influenced in the presence of 0.3 mumol/l dimetindene. The H2-selective agonist impromidine (0.001-0.3 mumol/l) had similar actions as histamine on spontaneously active Purkinje fibers, while the H1-selective agonist 2-(2-pyridyl-)ethylamine was ineffective. It is concluded that the pronounced stimulatory action of histamine on spontaneous activity in sheep cardiac Purkinje fibers is exclusively mediated by H2 receptors.

Action Potentials↗
PubMed1992

EGF receptor amplification and expression in human brain tumours.

Human epidermal growth factor receptor (EGFr) gene amplification, rearrangements and expression were studied in tumours of the human nervous system. EGFr gene amplification was studied in 46 brain tumours. Gene expression was analysed by northern blot in 37 tumours and binding of its protein to EGF in 27 tumours. The EGFr gene was simultaneously amplified (with arrangements in 12.5% of gliomas) and overexpressed in 53% (9/17) of malignant gliomas, but never in meningiomas. In five high grade gliomas, amplification was always associated with a high level of receptors. However, since high amounts of EGF receptors found in one glioma were not the result of gene amplification, several systems of deregulation in EGFr production may exist and could be located at translational and/or post-translational levels.

Adolescent↗
PubMed1992

Liver transplantation for erythropoietic protoporphyria. Report of a new case with subsequent medium-term follow-up.

We report a new case of successful liver transplantation in a 36-year-old patient with terminal hepatic failure due to erythropoietic protoporphyria. Data regarding protoporphyrin levels in erythrocytes and feces, before and after transplantation, seem to indicate that in this case protoporphyrin overproduction was in part due to liver synthesis. Four years after surgery, the patient is completely free of skin photosensitivity. His liver function tests are normal; there are no visible protoporphyrin deposits or ultrastructural abnormalities in his new liver. However, recurrence of the disease in the long term cannot be excluded, since erythrocyte protoporphyrin levels remained elevated after liver transplantation.

Adult↗
PubMed1992

t(2;18) and t(18;22) variant chromosomal translocations in B cell malignancies.

Variant translocations (2;18 and 18;22) are described in this review. The chromosomal and molecular findings of these translocation of BCL2 and their effect on possible BCL2 gene activation is discussed. Unanswered questions still remain and these include why this is so rare compared to the 25% incidence recorded for translocations in Burkitt's lymphoma. Further studies are obviously still needed in order to determine the true frequency of these findings and their distribution in the various B-cell disorders.

Animals↗
PubMed1992

[The EGF receptor pathway in human cerebral tumors].

The epidermal growth factor receptor gene is the most frequently involved proto-oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.F.) to tumor cells of the cystic wall has suggested investigation of possible "E.G.F.-like" autocrine activities in C.F. In 40% of gliomas, E.G.F.-R. gene is amplified and overexpressed. This is never observed in low grade astrocytomas. In 12% of the cases, mutations of the E.G.F.-R. gene are observed. In correlation with genomic abnormalities, E.G.F.-R. is immunoprecipitated in 40% gliomas. The basal phosphorylation of the receptor is increased in 50% gliomas. In C.F., unexpectedly, E.G.F.-R. phosphorylation inhibitory effect is observed. Its biochemical analysis suggests an anti-tyrosine kinase activity. The observation of anti-tyrosine kinase activity in C.Fs suggests the presence of negative modulatory factors of the proto-oncogene activation in tumor tissues. This could have therapeutical interest.

Blotting, Northern↗
PubMed1992

[Case report: anorexia nervosa in a 10-year-old boy].

A 10-year-old boy was admitted to the Children's Hospital with a 7-month history of disturbed eating behavior and a recent rapid weight loss: During the 24-day hospital stay the boy displayed a characteristic anorectic eating pattern, hyperactivity, anxiety, depression and compulsive behavior. Discharge followed a 4-kg weight gain. During the subsequent 12 months of outpatient care weight gain and eating behavior normalized. The boy's premorbid personality was described as compulsive and difficult. Although his intelligence was above average the boy had spelling problems and inadequate verbal skills. A change to a college-preparatory school and contact with a family with a vegetarian way of life probably precipitated the acute illness.

Anorexia Nervosa↗
PubMed1992

[Oncocytic presentation of a primary epithelioid leiomyosarcoma of the liver].

We report an epithelioid leiomyosarcoma of the liver with oncocytic differentiation. Initially misdiagnosed as an oncocytic endocrine tumor, analysis of the whole liver after transplantation permits rectification of the diagnosis. This observation outlines the fact that oncocytic differentiation is not restricted to epithelial cells but can also be encountered in cells of mesenchymal lineage.

Humans↗
PubMed1992

[Esophagectomy without thoracotomy for adenocarcinoma in Barrett's esophagus].

From April 1985 to November 1990, 12 patients with adenocarcinoma in a Barrett's esophagus, all of them men, with a median age of 62 years (range, 46 to 79 years), were operated by transhiatal esophagectomy and were submitted to a periodic follow-up. Dysphagia was the main symptom. Preoperative investigations included esogastroscopy and CT-scan of the abdomen and thorax in all patients. Esophageal endosonography was performed in the last 4 cases and MRI in one case. All patients recovered postoperatively and were discharged from hospital. The resected specimens were staged according to Rosenberg et al.'s classification: stage 1, 3 patients, stage 2, 2 patients, stage 3, 6 patients, stage 4, 1 patient. An anastomotic stricture occurred in 4 patients and was treated successfully by endoscopic dilatation. Five patients died during the follow-up period. Seven patients are alive without evidence of recurrence. Transhiatal esophagectomy appears to be the procedure of choice for adenocarcinoma arising from Barrett's esophagus.

Adenocarcinoma↗
PubMed1991

Accuracy of endosonography in the staging of rectal cancer treated by radiotherapy.

Endosonography is the best available method for the pretherapeutic staging of rectal cancer. The present prospective study was to determine the influence of previous radiotherapy, widely used in the management of this tumour, on the accuracy of endosonography. A complete endosonographic examination was performed just before surgery in 40 patients with rectal cancer. Endosonographic and pathological staging were compared in group A, 21 patients without previous radiotherapy, and group B, 19 patients with preoperative radiotherapy. While the endosonographic accuracy for lymph node involvement was similar in the two groups (85 per cent compared with 84 per cent), wall invasion was correctly ascertained in 86 per cent in group A but in only 47 per cent in group B (P less than 0.05). After irradiation, the thickening of the rectal wall and the poor visualization of the hyperechoic layers hampered interpretation. Post-radiotherapy inflammation and/or fibrosis probably explained the echographic changes. Radiotherapy therefore altered endosonographic staging of rectal cancer. New interpretation criteria are needed for evaluation and follow-up of rectal cancer treated by radiotherapy.

Adult↗
PubMed1991

Inhibition of potassium outward currents and pacemaker current in sheep cardiac Purkinje fibres by the verapamil derivative YS 035.

The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of -60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 mumols/l YS 035 APD-60 was increased to about 115% of reference. Prolongation measured as percentage of the respective control exhibited on the average no dependence on stimulation frequency (0.17-2 Hz). At 100 mumols/l membrane became depolarized to about -50 mV and action potentials could no longer be elicited. Further study was focussed on effects on outward currents, mostly activated at a frequency of 0.05 Hz. Transient outward current (ito) was completely blocked at 100 mumols/l and half-maximal inhibition occurred at about 14 mumols/l. Inwardly rectifying potassium current (ik1) was reduced to 47% of reference at 100 mumols/l. An initially activating outward current at positive membrane potentials (iinst) was reduced to 73% at 100 mumols/l. Time-dependent (delayed) outward current (iK) was on the average not affected up to 100 mumols/l. Besides inhibition of repolarizing outward currents YS 035 completely blocked pacemaker current (if) at 100 mumols/l and half-maximal reduction was achieved at 5 mumols/l. YS 035 (1-100 mumols/l) did not clearly affect time constants of activation at selected test potentials (IK: +35 mV; if: -90 mV) or inactivation (ito: 0 mV). Voltage-dependent control mechanisms of currents (ito, if) were not influenced by YS 035 but the amount of available current was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs.

PURPOSE: Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. PATIENTS AND METHODS: Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. RESULTS: Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. CONCLUSIONS: Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients.

Adolescent↗
PubMed1991

[Clinico-pathologic study of Kikuchi's necrotizing lymphadenitis. Report on 11 cases].

Histiocytic necrotizing lymphadenitis of Kikuchi is a rare benign disease. Characteristically, patients are young women with cervical adenopathy which may be associated with fever. Histologically, the involved lymph nodes show focal, well-circumscribed, paracortical, necrotizing lesions which contain karyorrhectic debris and aggregates of large mononuclear cells but no neutrophils. This disorder can be misdiagnosed as malignant lymphoma. The histological features seem to be related to delayed-type hypersensitivity but the antigenic stimulus is still unknown. The clinicopathological and immunohistochemical features of histiocytic necrotizing lymphadenitis in 11 patients are described. In necrotic areas, the majority of cells represent histiocytes and T cells (predominantly of CD8 phenotype). The involved lymph nodes were localized to several cervical sites (commonly jugular area).

Adolescent↗
PubMed1991

N-nitroso compounds, genotoxins and their precursors in gastric juice from humans with and without precancerous lesions of the stomach.

We are investigating the interrelationships between levels of total N-nitroso compounds (NOC), genotoxic activity (both before and after nitrosation), degree of bacterial colonization in gastric juice and degree of severity or absence of precancerous lesions of the stomach. The mean level of constitutive total NOC in gastric juice was similar in the different groups of patients, but it was higher in acidic gastric juice (n = 30) than in gastric juice at pH greater than 4.5 (n = 12). Acid-catalysed nitrosation of gastric juice in vitro increased the concentration of total NOC by up to several thousand fold, to a maximum of 1330 mumol/l. Genotoxicity, expressed as SOS-inducing potency per 100 microliters of gastric juice was measurable in only 20% of gastric juice samples tested. After acid-catalysed nitrosation, however, all samples showed genotoxic activity, the mean SOS-inducing potency being four to seven times greater than the corresponding constitutive value. There was no association between the mean SOS-inducing potency of gastric juice and the severity of precancerous lesions. The mean SOS-inducing potency of neutral or basic gastric juice was slightly greater than that of acidic samples. In a kinetic study on N-nitrosation of gastric juice in vitro, a mixture of amino and amido substrates was nitrosated; both qualitative and quantitative individual differences in nitrosatable substrates in gastric juice were seen. Fractionation of acidic, neutral and basic nitrosated gastric juice samples revealed a preponderance of nonvolatile, unknown NOC with varying polarities. The results of our study suggest that only pH determines the nature and level of precursors of NOC and of nitrosation-dependent genotoxins in gastric juice.

Adult↗
PubMed1991

Hepatic lesions in the rabbit induced by acoustic cavitation.

Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma.

Animals↗