Marie-Odile Peny

Intramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett's oesophagus.

BACKGROUND Eradication of Barretts mucosa by thermal or photoablation combined with high doses of proton pump inhibitors is a potentially attractive strategy in the management of this preneoplastic condition. However, major concerns of this method are the persistence of residual metaplastic glands beneath the new squamous epithelium and the absence of any knowledge of its impact on long term outcome. CASE REPORT The case of an intramucosal adenocarcinoma diagnosed 18 months after apparently complete squamous re-epithelialisation achieved using argon plasma coagulation and high dose omeprazole (40 mg/daily) is reported in a 68 year old patient presenting initially with a Barretts oesophagus without dysplasia. Intramucosal adenocarcinoma was located under the new squamous layer and presented as a bulging area covered by the squamous epithelium. It probably originates from residual metaplastic glands after therapy although a pre-existing tumour cannot be definitely excluded. CONCLUSION This observation might question future application of this experimental endotherapy in non-dysplastic Barretts oesophagus. It suggests that the residual glands might still be premalignant and that the early diagnosis of neoplastic changes might be compromised by the squamous re-epithelialisation.

Eradication of Barrett’s mucosa with argon plasma coagulation and acid suppression: immediate and mid term results

Background—Intestinal metaplastic mucosa in Barrett’s oesophagus can be replaced by squamous epithelium after mucosal thermal ablation associated with acid suppression therapy. Aims—To assess whether restoration of squamous epithelium can be obtained after ablation of Barrett’s oesophagus using argon plasma coagulation (APC) associated with proton pump inhibitor (PPI) therapy. Methods—Thirty one patients with Barrett’s oesophagus received APC. Omeprazole (40 mg/day) was given from the first APC application to one month after completion of the treatment, then given symptomatically. Twenty four hour pH-metry was performed during endotherapy. Results—Complete re-epithelialisation was visualised at endoscopy in 25/31 patients (81%) after a mean number of 2.4 APC sessions (range 1–4). Only partial squamous re-epithelialisation was observed in three patients and three others had no eradication. At histological assessment, eradication of Barrett’s oesophagus was only confirmed in 19/31 patients (61%) due to the presence of a few residual Barrett’s glands under the new squamous epithelium. Complete eradication was related to a Barrett’s oesophagus segment length of less than 4 cm and the absence of circumferential extension but not to the normalisation of oesophageal acid exposure under PPI therapy. Seventeen patients with apparently complete endoscopic and histological eradication of Barrett’s oesophagus were re-evaluated at one year; eight (47%) disclosed relapsing islands of Barrett metaplasia despite continuous omeprazole therapy (10–40 mg/day). Conclusions—APC combined with 40 mg omeprazole daily can eradicate Barrett’s mucosa with apparent squamous re-epithelialisation in the majority of patients even in the absence of normalisation of oesophageal acid exposure. However, one year after endotherapy for Barrett’s oesophagus, relapse is frequent but limited in extent.

Possible Mechanisms of Action of Transurethral Needle Ablation of the Prostate on Benign Prostatic Hyperplasia Symptoms: A Neurohistochemical Study

PURPOSE Transurethral needle ablation of benign prostatic hypertrophy (BPH) is a rapid, anesthesia-free outpatient procedure using low level radiofrequency energy that produces coagulative necrosis lesions at temperatures of approximately 100C. Clinically, significant improvement in objective and subjective parameters has been observed in BPH patients. Transurethral needle ablation has also been shown to be effective in relieving urinary retention. However, the precise mechanism of action of this procedure remains to be clarified. Ablation could produce its action on the dynamic component of the infravesical outlet obstruction. We analyzed the possible effects of transurethral needle ablation on the intraprostatic innervation. MATERIALS AND METHODS Histological sections from 10 open prostatectomy specimens (BPH) recovered 1 to 46 days after transurethral needle ablation were stained with hematoxylin and eosin and an immunohistochemical technique, using antibodies against S100 proteins and nonspecific enolase as specific nerve markers, and against anti-prostate specific antigen and anti-desmin for glandular and muscle cells, respectively. We used 5 BPH specimens as controls. RESULTS Microscopic examination of the treated areas showed necrotic lesions affecting epithelial and smooth muscle cells in the transition zone at a depth of 0.3 to 1.0 cm, from the preserved urethra. Nerve fibers in the control specimens and untreated prostatic areas were predominant in the urethral submucosal layer and in the stroma surrounding the epithelial nodules. No staining of any axon or isolated nerve cell was observed in any specimen treated by transurethral needle ablation, and there was a sharp and clear delineation between treated and untreated areas. CONCLUSIONS Our study demonstrated severe thermal damage to intraprostatic nerve fibers caused by transurethral needle ablation. A long-term denervation of alpha-receptors and/or sensory nerves could explain the clinical effects of transurethral needle ablation of the prostate. Theoretically, the best location to produce necrotic lesions should include submucosal and subcapsular nerve endings. Differences in the distribution of the adrenoreceptors and morphometry of the prostate transition zone could partly explain differences in clinical outcome observed after transurethral needle ablation of the prostate.

Reactivation of hepatitis B after transplantation in patients with pre-existing anti-hepatitis B surface antigen antibodies: report on three cases and review of the literature.

BACKGROUND Patients who have been exposed to the hepatitis B virus (HBV) and who were able to clear the hepatitis B surface antigen from the serum and to develop anti-hepatitis B surface antigen (anti-HBs) antibodies are not considered at risk for HBV reactivation after solid organ transplantation. METHODS AND RESULTS We, however, observed three solid organ transplant recipients who demonstrated clinically significant HBV reactivation after transplantation. All patients presented normal liver enzymes and serological stigmates of healed HBV infection at the time of transplantation, as indicated by the absence of hepatitis B surface antigen and the presence of anti-HBs and anti-hepatitis B core antibodies in the serum. Patient 1, a renal transplant recipient, presented HBV reactivation 3 years after transplantation and developed chronic HBV hepatitis. Patient 2 developed HBV reactivation 7 months after a second cadaveric renal graft and died of cirrhosis four and a half years after transplantation. Patient 3, a heart-lung transplant recipient, developed HBV reactivation within months after transplantation, but died of unrelated causes. HBV reactivation in the presence of anti-HBs antibodies has been previously reported in other settings of immunosuppression, mainly in patients with acquired immunodeficiency syndrome and after bone marrow transplantation, and may lead to fatal liver disease. Data from our renal transplant recipients suggest that the incidence of HBV reactivation among patients with anti-HBs and anti-hepatitis B core antibodies is about 5%. CONCLUSIONS Transplant physicians should be aware of the risk of HBV reactivation in patients presenting with healed HBV infection before transplantation.

Hepatocyte proliferative activity in human liver cirrhosis

BACKGROUND/AIMS The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor beta1 (TGFbeta1) as a possible correlate of hepatocyte proliferative activity. METHODS The present group (n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis. PCNA and TGFbeta1 immunostaining were analyzed on methanol-fixed, paraffin-embedded liver biopsies. RESULTS Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score. Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a significantly higher probability of survival than those with a PCNA-LI < or = 4.4% (0.87 vs 0.48, p=0.0009). TGFbeta1 expression in liver parenchyma correlated negatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis. CONCLUSIONS This prospective study strengthens our previous observation that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patients prognosis.

Transitional cell carcinoma of the bladder: evaluation of the role of human papillomaviruses

OBJECTIVES The study evaluated the conflicting results of the role of human papillomavirus (HPV) in the development of bladder carcinoma. METHODS We analyzed the frequency of HPV types 6, 11, 16, 18, and 33 by using polymerase chain reaction on formalin-fixed, paraffin-embedded specimens, from 75 cases of transitional cell carcinoma (TCC) of the bladder. Fifteen samples of normal urothelium adjacent to TCC (10) or from normal bladder obtained at autopsy (5) served as negative controls. RESULTS HPV type 16 deoxyribonucleic acid (DNA) was detected in 2 (2.7%) of the 75 cases of TCC and in none of the normal urinary bladder cases. The 2 patients with HPV type 16 were immunosuppressed after undergoing renal and cardiac transplantation. CONCLUSIONS These results strongly suggest that HPVs play a minor role in the development of TCC of the bladder in the general population, although they can act as oncogenic agents in predisposed patients, such as those who are immunosuppressed.

Demonstration of Human Papillomavirus Type 2 in a Verrucous Carcinoma of the Foot

This report describes one case of verrucous carcinoma of the foot containing human papillomavirus type 2 DNA which was detected by the polymerase chain reaction DNA amplification method. Our findings suggest that human papillomavirus type 2, which was classically associated with palmoplantar warts, may also play a role in the pathogenesis of peripheral verrucous carcinoma.

Verrucous carcinoma of the penis: Importance of human papillomavirus typing for diagnosis and therapeutic decision

One case of penile verrucous carcinoma (Buschke-Löwenstein tumor) undergoing anaplastic transformation and containing human papillomavirus type 6 is presented. The viral genome is detected by in situ hybridization using biotin-labeled cDNA probes. The clinical, histological and virologic criteria of verrucous carcinoma are discussed in comparison to giant condyloma and highly differentiated squamous cell carcinoma. The importance of viral typing determination for further diagnostic and therapeutic procedures is emphasized.

Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis

OBJECTIVE To analyze the expression of estrogen (ER) and progesterone (PR) receptors in the smooth muscle component (SMC) of deep infiltrating endometriosis (DIE). DESIGN A prospective clinical and pathologic study of 60 cases of DIE. SETTING University Hospital Department of Gynacology. PATIENT(S) Sixty patients with symptomatic DIE (uterosacral endometriosis n = 14; bladder endometriosis n = 10; colonic endometriosis n = 16; rectovaginal endometriosis n = 20). INTERVENTION(S) Laparoscopic surgery. MAIN OUTCOME MEASURE(S) The expression of ER and PR was studied by immunohistochemistry in the SMC directly around endometriotic foci and at distance (at least >1.5 cm) from them in correlation with proliferative and secretory phases of cycle. RESULTS The ER and PR were present in the SMC of DEI in each location excepting colonic endometriosis where ER were absent. Independently of cycles phases the PR were more abundant than ER. With the exception of rectovaginal endometriosis, where the ER and PR were more abundant in the proliferative than in the secretory phase, in other locations the ER and PR did not differ significantly with cycles phases. Last, if ER and PR were more abundant in SMC around endometriotic foci than at a distance from them. However, the difference was not significant. CONCLUSIONS Our data substantially confirm for the first time that in various forms of DIE, ER and PR are present not only in glands and stroma but also in the smooth muscle major histologic component of this disease.

Proliferating cell nuclear antigen distribution in verrucous carcinoma of the skin.

Verrucous carcinoma (VC) of the skin is a rare variety of well‐differentiated squamous cell carcinoma (SCC) characterized by aggressive local growth and a low metastatic potential. These tumours are known to have histological and virological features similar to classic warts or condylomata. The aim of the present study was to map the proliferative compartment in VC (n=7) in comparison with warts (n=10) and typical well‐differtntiated SCC (n=10). The proliferating cells were detected by immunostaining of proliferating cell nuclear antigen (PCNA) in formalin‐fixed, paraffin‐embedded tissue sections, using the commercially available anti‐PCNA monoclonal antibody PC10. Normal epidermis served as a positive control and reference. In VC and warts, the PCNA‐positive cells were principally located at the periphery of lesions, in the basal layer of the tumour islands. In some warts, however, stronger PCNA expressed was noted in the superficial layers, of the lesions corresponding to virus‐infected keratinocytes (koilocytotic cells). In contrast, in SCC, PCNA‐positive cells were randomly scattered throughout the tumours.