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Biomedical subjects

M O Peny

Publications and source records attributed to M O Peny.

At least 19 recordsLinked to original sources

Argon plasma coagulation in the treatment of Barrett's high-grade dysplasia and in situ adenocarcinoma.

BACKGROUND AND STUDY AIMS: Endoscopic therapy of high-grade dysplasia (HGD) and superficial adenocarcinoma associated with Barrett's esophagus (BE), using Nd:YAG laser, KTP laser, or photodynamic therapy (PDT), has been reported to be effective in a curative role. Argon plasma coagulation (APC) appears to be effective in the eradication of nondysplastic Barrett's mucosa, but no results are available in the management of early neoplasms complicating BE. We report our initial experience in the application of APC in this indication. PATIENTS AND METHODS: Ten patients (mean age 74.2) with histologically proven HGD (n = 7) or in situ adenocarcinoma (n = 3) associated with BE (mean length 6 cm) and unfit for surgery were treated using APC and high-dose omeprazole (40 mg daily) until squamous re-epithelialization or complete eradication of the initially apparent lesions. Endoscopic follow-up was maintained at every 3 months. RESULTS: Complete eradication of HGD and in situ adenocarcinoma was achieved after a mean number of 3.3+/-1.5 APC sessions in 8/10 patients (80%). The eight patients with complete clearance of the neoplastic areas did not show any evidence of local recurrence during a median follow-up of 24 months (range 12-36 months). One patient with initial HGD had persistence of HGD 30 months after initial diagnosis, and one patient progressed to invasive adenocarcinoma after failure of APC and PDT. CONCLUSIONS: APC is safe and effective in the management of HGD and in situ adenocarcinoma associated with BE, and might represent an interesting alternative in selected patients who are not candidates for surgery.

Adenocarcinoma↗

Repeated concanavalin A challenge in mice induces an interleukin 10-producing phenotype and liver fibrosis.

Weekly injections of Concanavalin A (Con A) were performed in BALB/c mice to evaluate the pattern of cytokine production and liver injury. High serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), IL-4, and interferon gamma (IFN-gamma) were found in the serum after the first 2 injections of Con A but rapidly decreased from the third injection. Conversely, IL-10 serum levels after repeated Con A challenge increased by 7 times from week 1 to 20. In vivo depletion studies indicated that CD4(+) T cells are essential in IL-10 production. Hepatocyte necrosis was only observed after the first injections of Con A whereas centrilobular inflammatory infiltrates persisted up to 20 weeks. Perisinusoidal liver fibrosis was also increasingly detected in BALB/c mice, whereas no fibrous change was observed in nude mice after 6 weeks of Con A challenge. The number of stellate cells, detected by immunostaining, increased after 20 weeks of Con A injections. Liver cytokine messenger RNA (mRNA) expression after 20 weeks showed expression of transforming growth factor beta1 (TGF-beta1), IL-10, and IL-4 whereas IL-2 was no more expressed. The present study shows that mice repeatedly injected with Con A develop liver fibrosis. The cytokine-release pattern observed after 1 injection of Con A is rapidly shifted towards an immunomodulatory phenotype characterized by the systemic production of large amounts of IL-10.

Animals↗

Localized amyloid tumor in small bowel.

We report a case of localized jejunal amyloidosis occurring in a 74-year-old man who experienced an episode of digestive bleeding while he was receiving oral anticoagulation. It illustrates a rare entity, characterized by an endoscopic aspect of polypoid, pseudotumoral formations. Histologically, submucosal connective tissues, muscularis mucosae, and blood vessel walls are massively infiltrated by amyloid, giving a typical red/green birefringence under polarized light.

Aged↗

Overexpression of 27-kDa heat shock protein relates to poor histological differentiation in human oesophageal squamous cell carcinoma.

AIMS: Various stress conditions such as heat, chemical and mechanical stresses are known to play a major role in oesophageal squamous cell carcinoma development. Our goal was to evaluate whether changes in stress-induced 27-kDa heat shock protein (HSP27) expression could be demonstrated during oesophageal carcinogenesis. METHODS AND RESULTS: HSP27 expression was studied using immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections from 21 oesophageal squamous cell carcinomas occurring in smokers and/or alcohol abusers. Oesophagus from healthy patients (controls) (five), chemical (eight) and infectious oesophagitis (six) were also included in the study. In normal oesophagus, the protein is present only in the upper epithelial layers. In contrast, in chemical or infectious oesophagitis its expression is strong and occurs in all the epithelial layers including the basal layer. In non-tumoral oesophageal mucosa from smoking and/or drinking patients adjacent to invasive carcinoma, the distribution of the protein is patchy and irregular. In malignant areas, HSP27 protein expression increases drastically from dysplastic lesions to invasive carcinoma, being highest in the less differentiated areas. CONCLUSIONS: In human oesophagus, HSP27 expression is induced by various stresses but alcohol and tobacco generate focal perturbations in the stress response. Tumour immunoreactivity for this protein increases with the anaplasia of the tumour, as in some other tumours in which it is considered to play a role in drug resistance. To our knowledge, these data have not been previously described for oesophageal squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Sigmoid endometriosis and ovarian stimulation.

In-vitro fertilization (IVF) and ovarian stimulation are frequently performed in patients with endometriosis. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low. We report four cases of severe digestive complications due to the rapid growth of sigmoid endometriosis under ovarian stimulation. In three patients, sigmoid endometriosis was diagnosed at laparoscopy for sterility. Because of the absence of digestive symptoms or repercussion on the bowel, no bowel resection was performed before ovarian stimulation. All patients experienced severe digestive symptoms during ovarian stimulation, and a segmental sigmoid resection had to be performed. Analysis of endoscopic and radiological data demonstrated that bowel lesions of small size may rapidly enlarge and become highly symptomatic under ovarian stimulation. At immunohistochemistry, these infiltrating lesions displayed high populations of steroid receptors and a high proliferative index (Ki-67 activity), suggesting a strong dependence on circulating ovarian hormones and a potential for rapid growth under supraphysiological oestrogen concentrations. Clinicians should be aware of this rare but severe digestive complication of ovarian stimulation. The early diagnosis of such lesions may help the patients to avoid months of morbidity falsely attributed to ovarian stimulation side effects. Further experience is necessary to determine the optimal attitude when diagnosing a small and asymptomatic endometriotic bowel lesion before ovarian stimulation.

Adult↗

Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules.

The histological relationships between fibrotic tissue, endometriotic foci and nerves in the rectovaginal septum endometriotic or adenomyotic nodule were studied. This is considered to be one of the most severe forms of deep endometriosis. Masson's trichrome staining for fibrosis detection and immunohistochemistry with the S100 monoclonal antibody for nerve detection were performed in 28 rectovaginal endometriotic nodules from patients presenting with severe dysmenorrhoea and deep dyspareunia (23 patients with no other endometriotic location or potential cause of pain at laparoscopy and ultrasonography; five patients with multiple pelvic endometriotic localizations and other potential causes of pain at laparoscopy). Patients were allocated to two groups on the basis of their preoperative pain scores for pelvic pain, dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7). For each symptom, the mean number of nerves and endometriotic lesions per high-power field and the mean largest diameter of the lesions were not statistically different in groups 1 and 2. The mean percentages of nerves located within the fibrosis of the nodule and within endometriotic lesions were significantly higher in group 1 than in group 2. Among nerves located within endometriotic lesions, there was a significantly higher proportion showing intraneurial and perineurial invasion by endometriosis in group 1 than in group 2. In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometriotic foci, and between nerves and the fibrotic component of the nodule. We postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.

Adult↗

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

BACKGROUND: Eradication of Barrett's 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 Barrett's 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 Barrett's 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.

Adenocarcinoma↗

Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin.

We studied the hepato-splanchnic vascular response and changes in O2 extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2 delivery (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3 +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg. min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2 supply-dependent simultaneously.

Animals↗

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 patient's prognosis.

Biopsy↗

Sporadic carcinoid of the stomach: a highly proliferative disease with a probable role for p53 protein dysregulation.

We describe here one case of sporadic carcinoid of the stomach, occurring in a 65-year-old man. It is a rare, recently recognized entity, with only few cases reported in the literature. We were able to detect strong MIB-1 and p53 expression in this tumour, with 86 and 80% of tumoral cells positive, respectively. These data suggest that gastric sporadic carcinoids are a highly proliferative entity probably induced by dysregulation of p53 function.

Aged↗

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.

Adult↗

Role of the double-contrast barium enema in rectal stenosis due to suppositories containing paracetamol and acetylsalicylic acid.

Self-treatment of chronic headache with suppositories containing paracetamol and acetylsalicylic acid may lead to serious complications. We report the radiological features of five cases of rectal stenosis following the use of such suppositories. The role of the double-contrast barium enema in suggesting the diagnosis of this complication of a chronic and often unrecognized self-treatment is emphasized.

Adult↗

Expression of transforming growth factor beta receptors in normal human colon and sporadic adenocarcinomas.

BACKGROUND & AIMS: An absence or a presence of mutated transforming growth factor (TGF)-beta receptors is a possible hypothesis explaining the resistance of cancer cells to the growth-inhibitory effect of TGF-beta. Mutations involving microsatellite-like regions of the type II TGF-beta receptor have been described in subgroups of colorectal cancers. The aim of this study was to investigate the expression and distribution of TGF-beta receptors in sporadic colorectal cancers and normal tissues. METHODS: Thirty-three sporadic colorectal cancers and 20 normal colonic tissues were explored by immunohistochemistry for the expression of type I and type II TGF-beta receptors. Eighteen tumor and 20 normal samples were used for radioactive thermocycling and sequencing of the two microsatellite-like regions of the type II receptor. RESULTS: Both receptors were overexpressed in tumors compared with normal samples. There was a relationship between the abundance of type II receptor expression and the degree of differentiation of the tumors but not the Dukes' staging or the localization of the neoplasias. No mutation was observed in the microsatellite-like regions of receptor II in any of the samples. CONCLUSIONS: Sporadic colorectal cancers do not show an absence or a presence of mutated TGF-beta receptors that could explain a resistance to TGF-beta-mediated growth inhibition. The pathways to tumorigenesis of sporadic colorectal cancers may be different from those of some hereditary ones.

Adenocarcinoma↗

Adventitial cystic disease of the popliteal artery communicating with the knee joint. A case report.

We describe the case of a patient with adventitial cystic disease of the popliteal artery in which a direct anatomic communication between the cysts and the nearby knee joint was demonstrated by magnetic resonance imaging and confirmed by surgery. This unusual observation could shed some light on the much debated question of the cause, the pathogenesis, and the management of the affection. Moreover, it emphasizes the importance and the role of magnetic resonance imaging in the diagnosis of adventitial cystic disease of the popliteal artery.

Adult↗