Conformational analyses on histamine H2-receptor antagonists.

In a series of compounds with H2-antihistaminic activity, a conformational analysis was performed based on force field calculations. The drugs studied were cimetidine, ranitidine, famotidine, roxatidine and the conformationally more restricted ICI127032. For the compounds containing a flexible chain, the local minima conformations and the global minimum conformation were calculated. These conformations were used for a systematic structural comparison with all energetically allowed conformations of the ICI derivative, with regard to the best fit of the common structural features. In this way a pharmacophore could be developed consisting of four parts: (1) a polar planar group, uncharged at physiological pH; (2) a hydrophobic part formed by aromatic systems or flexible chains; (3) an--under physiological conditions--protonated nitrogen atom; and (4) a substructure, which contains a hydrogen bond donor site and a hydrogen bond acceptor site in a specific spatial arrangement.

[Malignant mesothelioma of the pleura. Analysis of its immunohistochemical aspects]. / Mésothéliomes malins de la plèvre. Analyse de leurs aspects immunohistochimiques.

To evaluate the usefulness of immunohistochemistry in the diagnostic distinction between pleural mesothelioma and metastatic adenocarcinoma to the pleura, the authors studied formalin-fixed paraffin-embedded tissue sections from 14 pleural mesotheliomas and 20 primary adenocarcinomas of the lung, stomach, ovary and breast by using 16 commercially available antibodies to cytokeratin (KL1), vimentin, EMA, CEA, CA19.9, CA125, Egp 34 (detected by HEA 125), secretory component, S100 protein, SP1-béta 1, Leu M1, alpha-1-AT, alpha-1-ACT, lysozyme, desmin and factor VIII. Keratin positivity was found in all mesotheliomas and adenocarcinomas. A coexpression of keratin and vimentin was present in 8/14 (57%) mesotheliomas but only in 2/20 (10%) adenocarcinomas. CEA and CA 19.9 were detected in 80% and 65% of the adenocarcinomas respectively, but not in any of the mesotheliomas. Interestingly, two adenocarcinomas (of the ovary and the stomach) that failed to stain for CEA, were immunoreactive to anti-CA 19.9 antibody. Thus, the combined use of anti-CEA and anti-CA 19.9 antibodies results in staining 90% of the adenocarcinomas. S100 protein, SP1-beta and Leu M1 were also absent in mesotheliomas but present only in less than half of the adenocarcinomas. Adenocarcinomas and mesotheliomas did not significantly vary in reaction to the remaining above mentioned antibodies. The authors conclude that the coexpression of keratin and vimentin and the absence of CEA and CA 19.9 might be the best criteria in the distinction of mesothelioma from metastatic non mucosecreting adenocarcinoma.

[Blind-pouch syndrome after side-to-side intestinal anastomosis]. / Le syndrome de la poche aveugle après anastomoses intestinales latéro-latérales.

Side-to-side anastomosis is a bad technique to restore intestinal continuity. In fact, it leads to the progressive distention of the cul-de-sac, which produces definite pockets of stasis and bacterial infection. Although it is well tolerated by a number of patients, it causes a number of gathered complications in others. This array of signs is called the blind pocket syndrome, the characteristics of which are described by the authors on the basis of a 76-case series, including 3 personal cases. They again condemn the side-to-side anastomosis and prefer end-to-end anastomosis, which prevents these disadvantages.

[Malignant peritoneal mesothelioma in a child. Diagnostic difficulties in a locally "non tumoral" form, revealed by cervical lymph node metastasis]. / Mésothéliome malin péritonéal chez un enfant. Difficultés diagnostiques devant une forme localement "non tumorale", à présentation métastatique ganglionnaire cervicale.

We report the unusual case-history of a ten-year-old girl who presented with enlarged cervical and supraclavicular lymph nodes apparently due to sinus histiocytosis upon initial histological evaluation. However, they were shown to be nodal metastases from an epithelial form of malignant mesothelioma coexpressing keratin, vimentin, and desmin. Exploratory laparotomy disclosed a diffuse "non tumoral" peritoneal mesothelioma. The neoplastic cells were so highly differentiated that analysis of peritoneal fluid pointed to reactive mesothelial hyperplasia. Intensive combination chemotherapy failed to achieve complete remission, but the child's condition was satisfactory after two and a half years follow-up. On the basis of data from the literature, we review the course, immunohistochemical features, and differential diagnosis of malignant peritoneal mesothelioma.

[Therapeutic problems of intra-abdominal liposarcoma]. / Problèmes thérapeutiques posés par les liposarcomes intra-abdominaux.

Intra-abdominal liposarcomas are very rare tumors. We present our personal experience with one case of mesenteric liposarcoma which had perforated into the peritoneal cavity, occurring in a seven-month pregnant female patient. Seven years later, the patient is doing well. The authors have carried out a review of the literature. In addition to liposarcomas of the mesentery and the mesocolon, they observed some cases of liposarcoma localized in the omentum and the stomach; other abdominal localizations occurred sporadically. Radical surgical excision was the choice treatment. Both the propensity for locoregional spread and the histological diversity set the conditions for prognosis; the latter seemed minimally influenced by either radio- or chemotherapy.

[Hepatic undifferentiated (or embryonal) sarcoma. Diagnostic and therapeutic problems apropos of botryoid rhabdomyosarcoma]. / Sarcomes indifférenciés (ou embryonnaires) hépatiques. Problèmes diagnostiques et thérapeutiques à propos d'un rhabdomyosarcome botryoïde.

Primary undifferentiated sarcomas (also called embryonal sarcomas or malignant mesenchymomas) are an exceptional form of cancer of the liver, occurring preferentially in children or adolescents. They can exhibit poor differentiation, embryonal rhabdomyosarcoma being the most frequent. To date, therapeutic success has been reported only rarely. The authors describe the case of a 16 year old boy with primary hepatic sarcoma showing a rhabdomyoblastic differentiation, who is in complete remission two years after total surgical resection and polychemotherapy.

Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa.

The human pS2 gene is specifically expressed under estrogen transcriptional control in a subclass of estrogen receptor-containing human breast cancer cells. The pS2 gene encodes an 84-amino acid protein that is secreted after signal peptide cleavage. The distribution of pS2 protein in normal human tissues was studied with antibodies to pS2; pS2 was specifically expressed and secreted by mucosa cells of the normal stomach antrum and body of both female and male individuals. Moreover, no estrogen receptor could be detected in these cells, indicating that pS2 gene expression is estrogen-independent in the stomach. The function of the pS2 protein in the gastrointestinal tract is unknown. However, the pS2 protein is similar in sequence to a porcine pancreatic protein that has been shown to inhibit gastrointestinal motility and gastric secretion.

[Uninodular bronchiolo-alveolar cancer. Apropos of 5 cases with a prolonged course]. / Les cancers bronchiolo-alvéolaires uninodulaires. A propos de 5 cas d'évolution prolongée.

Five cases of uninodular bronchioloalveolar cell (BAC) carcinoma are reported. These 5 cases were characterized by the protracted course of the disease: 14.5 and 11.5 years respectively in the 2 patients who died; 7.5, 12 and 12.5 years respectively in the 3 patients who are still alive. Prior to being diagnosed at excision, the tumours had been followed up for an unusual 2 to 10 years period, with phases of radiological stability and phases of very slow growth. This very slow course is exceptional in lung cancer. It differs not only from the course of diffuse BAC carcinoma, but also from the habitual course of uninodular BAC carcinoma and from that of peripheral adenocarcinoma. Similar cases could be found in the literature, and a comparative study has been conducted between these slow-course carcinomas and normal-course carcinomas. Whatever their outcome, slow-course carcinomas are asymptomatic tumours which present at radiography of the chest as a peripheral round or oval opacity devoid of pathognomonic features. The post-operative prognosis of slow-course tumours seems to be more favourable than that of the other lung cancers. At histology, carcinomas with a protracted course usually show a pattern similar to that of lesions called by some authors "benign adenomatosis"; however, some of these tumours exhibit fairly distinct signs of malignancy, and electron microscopic images also are far from being uniform.

[A case of pheochromocytoma with cardiac localization. Review of the literature]. / Un cas de phéochromocytome à localisation cardiaque. Revue de la littérature.

In a 26-year old man who died post-operatively, post-mortem examination revealed the presence of a phaeochromocytoma located in the atrio-ventricular sulcus and involving the trunk and bifurcation branches of the left coronary artery. Pre-operative investigations, including whole-body computerized tomography, and exploratory laparotomy had failed to detect the tumour. In contrast with the case reported here, the 4 other cases previously published concerned intrapericardial phaeochromocytomas in contact with the posterior wall of the left atrium.

[Well differentiated adenocarcinoma ("yellow cancer") of the prostate. Problems of diagnosis and prognosis (author's transl)]. / L'adénocarcinome très différencié ("yellow cancer") de la prostate. Problèmes de diagnostic et de pronostic.

This paper reports the case of a very large hyperdifferentiated prostatic adenocarcinoma, characterized by a very high lipid content; there is little information in the literature about diagnosis and prognosis of this rare type of cancer. Relevant characteristics of this tumor were its middle prostatic location, its soft consistency and its homogeneous yellow appearance (the so called "yellow cancer") - In spite of its large size, the growth remained confined to the prostate. The histological aspect of this cancer is close to intense glandular hyperplasia, so the differential diagnosis is quite difficult on scanty biopsy samples without lipid stains.

[Urothelial bladder carcinoma in situ involving the whole urinary tract. One case (author's transl)]. / Carcinome urothélial in situ étendu à tout l'arbre urinaire. A propos d'un cas.

We report a case of urothelial carcinoma in situ extended to the whole excreto-urinary tract and involving the prostatic gland and the papillary ducts of the kidney. The patient was followed up for almost five years. The evolution was unfavorable, as multifocal invasion appeared. We emphasize the difficulties of the pathological diagnosis on biopsy samples and relate the usual behaviour of this type of cancer who may often simulate an interstitial cystitis. Because of uncertain prognosis and difficulties in the evaluation of the disease, the optimal management for such patients remains imprecise in spite of the benefit of cytologic surveillance. Thus, in the absence of obvious invasion the choice of treatment depends at time on morphological data as well as on topographic and functional criteria.