Freddy J. Cornillie

Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease.

OBJECTIVES:Although the clinical efficacy of infliximab as measured by closure of fistulas in Crohns disease has been demonstrated, its influence on the inflammatory changes in the fistula tracks is less clear. The aim of the present study was to assess the behavior of perianal fistulas before and after infliximab treatment.METHODS:Magnetic resonance imaging (MRI) and clinical evaluation were performed in a total of 18 patients before and after treatment with infliximab. An MRI-based score of perianal Crohns disease severity was developed using both criteria of local extension of fistulas (complexity, supralavetoric extension, relation to the sphincters and of active inflammation (T2 hyperintensity, presence of cavities/abscesses, and rectal wall involvement).RESULTS:The MRI score was reliable in assessing the fistula tracks, with a good interobserver concordance (p < 0.001). Fistula tracks with signs of active inflammation were found in all 18 patients at baseline and collections in seven. After short-term infliximab treatment, active tracks persisted in eight of 11 patients who had clinically responded to infliximab. After long-term (46 wk) infliximab therapy, MRI signs of active track inflammation had resolved in three of six patients.CONCLUSIONS:We have developed an MRI-based score of perianal Crohns disease severity to assess the anatomical evolution of Crohns fistulas. Our study demonstrates that despite closure of draining external orifices after infliximab therapy, fistula tracks persist with varying degrees of residual inflammation, which may cause recurrent fistulas and pelvic abscesses. Whether complete fistula fibrosis occurs over time with repeated infliximab infusions needs further study.

Infliximab induces potent anti‐inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn’s disease

Anti‐TNFα therapy with infliximab is effective for Crohn’s disease. Infliximab neutralizes the biological activities of TNFα, a cytokine involved in host‐defence against certain infections.

Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration * †

OBJECTIVESnTo evaluate a clinical examination during menstruation and plasma CA-125 concentrations to diagnose deep endometriosis.nnnDESIGNnProspective study in 61 women scheduled for a laparoscopy, a retrospective study in 140 women with deep endometriosis, and a clinical validation study in 16 women with painful pelvic nodularities during menstruation.nnnSETTINGnUniversity Hospital Gasthuisberg, a tertiary referral center.nnnRESULTSnIn the retrospective study, deep endometriosis was detected by routine clinical examination in only 36% of women. Lesions infiltrating deeper than 15 mm were detected in 50%. In the prospective study pelvic nodularities were detected by routine clinical examination in 4 women but were detected in 22 by clinical examination during menstruation. The latter was highly reliable to diagnose deep endometriosis, cystic ovarian endometriosis, and cul-de-sac obliteration. CA-125 concentrations were higher during menstruation and correlated with deep endometriosis and with deep and cystic ovarian endometriosis. Nodularities at clinical examination or follicular phase CA-125 concentrations > 35 U/mL are useful to decide that a bowel preparation should be given, achieving a sensitivity of 87% and a specificity of 83%. In the clinical validation study, deep endometriosis was found in 14 of 16 women.nnnCONCLUSIONnClinical examination during menstruation can diagnose reliably deep endometriosis, cystic ovarian endometriosis, or cul-de-sac adhesions. This test, preferentially combined with a follicular phase CA-125 assay, should be used to decide whether a preparation for bowel surgery should be given.

Peritoneal endometriosis: scanning electron microscopy and histology of minimal pelvic endometriotic lesions

In 36 patients with laparoscopically diagnosed endometriosis, biopsies were taken from different areas of the pelvic peritoneum bearing foci of endometriosis. The biopsies were studied by scanning electron microscopy and by light microscopy. Combined use of these techniques resulted in the differentiation of three topographically and morphologically different types of endometriotic lesions: intraperitoneal endometriotic polyps with no glandular openings but associated with deeper endometriotic glands and stroma; intraperitoneal endometriotic foci with surface epithelium, glands, and stroma; and retroperitoneal small lesions with few glands and scant stroma. The morphologic features of endometriotic foci indicate that they do not follow the typical cyclic changes described for the uterine endometrium. Our microanatomic characterization of endometriosis is discussed in relation to the conflicting data concerning peritoneal fluid constituents and infertility in patients with minimal endometriotic lesions.

Free-to-Total Prostate Specific Antigen Ratio as a Single Test for Detection of Significant Stage T1c Prostate Cancer

PURPOSEnWe investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels.nnnMATERIALS AND METHODSnThe specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77% underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens.nnnRESULTSnBenign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-toal PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84% of stage T1c cancers were significant and comparable to stage T2 or greater cancers.nnnCONCLUSIONSnFree-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.

Atypical Bronchial Cilia in Children with Recurrent Respiratory Tract Infections: A Comparative Ultrastructural Study*

Ultrastructurally atypical bronchial cilia are studied and semiquantitatively analysed in 24 children suffering from recurrent respiratory tract infections with or without bronchiectasis. In patients with Kartageners syndrome normal-looking and shortened dynein arms are present at some axonemal microtubular doublets. This finding suggests that the polymerization or assemblage of dynein molecules on microtubules only is defective but not totally lacking. Bilateral, local and partial absence of dynein arms is demonstrated in some of the patients with acquired unilateral bronchiectases. These patients also reveal anomalies of the 9 + 2 microtubular axonemal pattern. It is suggested that these abnormalities of the tubulin-dynein system are local and acquired defects that may impair bronchial mucociliary clearance. None of the patients with pneumonia and asthma or with cystic fibrosis studied show any anomalies of the dynein arms. However aberrant axonemal microtubular patterns and other ciliopathies such as naked axonemes and megacilia are present at times in these patients. We postulate that these atypical cilia are secondary acquired abnormalities. Only some patients with bacterial or viral pneumonia demonstrate a partial lack of dynein arms in bronchial cilia. Other ciliopathies such as megacilia, naked and intracytoplasmic axonemes and apical blebs are more frequent and more common in these patients. We suppose they manifest a secondary and rather aspecific pathogenic influence upon the bronchial ciliary substructure.

The response of human endometriotic implants to the anti-progesterone steroid R 2323: a histologic and ultrastructural study.

The histology and ultrastructure of small endometriotic lesions were studied in 19 patients before and after hormonal therapy with the anti-progesterone steroid R 2323 (Gestrinone). Histologic results demonstrate that treatment of endometriosis with this steroid does not result in complete elimination of the endometriotic foci, although glandular proliferation and secretion are arrested in most implants. The ultrastructural results indicate that this inhibition of proliferation and secretion is related to an enhanced activity of the lysosomal system in the epithelial cells of some endometriotic foci. In other implants, or even in other cells of the same foci, epithelial cells with only a small amount of supranuclear cytoplasm but lacking lysosomes may be found. The morphologic data demonstrate that the cellular involutionary response to the antiprogesterone drug Gestrinone involves an activation of the lysosomal system, an abortive apocrine secretion of cell remnants and finally, in some implants, an extrusion of individual epithelial cells. Since this involutionary process of endometriotic cells mimics the pre-menstrual lysosomal degradation in the endometrium, it is suggested that the competitive binding of the antiprogesterone Gestrinone to the progesterone receptors of endometriotic epithelium may cause a cellular progesterone withdrawal effect.

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis**Presented in part at the 7th World Congress on Human Reproduction, Helsinki, Finland, June 26, 1990.††Supported by grant 9.0020.90 from the Belgian Fonds voor Wetenschappelijk Onderzoek, Brussels, Belgium; and by grants from the Academy of Finland and the Sigrid Juselius Foundation, Helsinki, Finland.

OBJECTIVEnTo investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis.nnnDESIGNnPlasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility.nnnMAIN OUTCOME MEASUREnThe presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts.nnnRESULTSnPeritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL.nnnCONCLUSIONnSuperficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.