Splenic metastasis from gastrointestinal neoplasms: a review.

Spleen metastases from solid tumours are rather exceptional, especially for those located in the digestive tract. Although these lesions are usually associated with multivisceral disease at terminal stage, several cases of isolated lesions have also been described in the literature. Diagnosis of spleen lesions associated with multivisceral disease rarely influences patient's outcome. On the other hand, isolated, only-splenic lesions could be curatively treated, allowing physicians to obtain better patient's survival. The aim of this article is therefore to review and summarize a systematic search of all the literature in English based on a Medline search (Pubmed) carried out from January 2000 to February 2011, focusing on only-spleen lesions secondary to digestive tract cancers, and pointing out diagnostic and treatment challenges medical oncologists have to face in their clinical practice.

Macroscopic endoscopic lesions in microscopic collagenous colitis: double case report and review of the literature.

Collagenous colitis is a cause of chronic diarrhea of incompletely elucidated origin, defined by normal laboratory tests, a normal endoscopic appearance of colonic mucosa and specific microscopic inflammatory features on colonic biopsies. We report two cases of macroscopic endoscopic lesions observed in patients suffering from chronic diarrhea, whose biopsies confirmed a diagnosis of collagenous colitis and who were successfully treated in that setting, achieving clinical and endoscopic remissions. By means of a literature review, we summarize what is known about collagenous colitis. We particularly discuss macroscopic findings in that context, drawing attention on the so called "microscopic colitis" in the differential diagnosis of that type of lesions.

Fatal hypoxic hepatitis in a patient with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease).

Hypoxic (ischemic) hepatitis generally requires the concurrence of an underlying condition which chronically exposes the liver to some degree of hypoxia (for example, congestive heart failure) combined with a triggering event (for example, arrhythmia) which further decreases the oxygen supply. We report a case of hypoxic hepatitis in which hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease) constituted this underlying condition and gastrointestinal hemorrhage was the triggering event. To our knowledge, this is the first reported case of hypoxic hepatitis in hereditary hemorrhagic telangiectasia with the exception of therapeutic ligation or embolization of the hepatic artery so as to decrease shunting of liver blood. Hemodynamic mechanisms are proposed to explain this particular outcome.

Black pigments in the liver related to gold and titanium deposits. A report of four cases.

Black pigments are rarely described in the liver. We report four patients with chronic cholestasis and black pigments described on liver histological examination. Energy-dispersive X-ray analysis identified these black pigments as gold particles in the first three patients and titanium particles in the fourth. The origin of the gold deposits was unknown in this first patient and related to gold salts therapy in the two others. Titanium deposits was associated with hepatic granulomas and related to total knee replacement.

Warty carcinoma of the anus: a variant of squamous cell carcinoma associated with anal intraepithelial neoplasia and human papillomavirus infection.

Warty carcinoma (WC) is a rare variant of squamous cell carcinoma primarily described in the vulva in younger women and classically associated with human papillomavirus (HPV) infection. The gross findings are similar to those of verrucous carcinoma with large, exophytic tumors with a papillomatous surface. Microscopically, the tumor is papillated and contains fibrovascular cores covered by hyperkeratotic epithelium showing presence of koilocytes. We report a case of anal squamous cell carcinoma showing similar features, occurring in a young immunosuppressed male patient with a history of multifocal anal intraepithelial neoplasia (AIN). HPV-16 has been demonstrated both in the WC and in adjacent AIN, but the HPV status appears different in the two lesions: integrated in WC and episomal in AIN lesions. We also have demonstrated by immunohistochemistry that both WC and AIN are highly proliferative entities sharing the same MIB-1 pattern, and that WAF1/CIP1 protein expression is common in the two lesions irrespective of p53 protein expression.

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.

Retrospective analysis of 29 patients surgically treated for hepatocellular adenoma or focal nodular hyperplasia.

BACKGROUND/AIMS: Hepatocellular adenoma resection and focal nodular hyperplasia supervision are widely recognized as the best management when these benign liver tumors are diagnosed. Differential diagnosis is thus mandatory. METHODOLOGY: Twenty-nine patients with a presumed benign liver tumor were retrospectively analyzed. RESULTS: Histopathological analysis of these resected liver tumors demonstrated hepatocellular adenoma in 16 patients and focal nodular hyperplasia in 13. One hepatocellular carcinoma was disclosed into a hepatocellular adenoma and 2 hepatocellular adenoma showed foci of liver-cell dysplasia. Seven patients with hepatocellular adenoma (43%) had evidence of intratumoral hemorrhage, among which 3 patients were admitted with intraperitoneal tumoral rupture. Computed tomography, performed in 26 patients, was the most reliable examination to characterize these presumed benign liver tumors. Magnetic resonance imaging concerned only 5 patients but 3 hepatocellular adenoma and 1 focal nodular hyperplasia were diagnosed. The indications of focal nodular hyperplasia surgical resection were chronic pain (4 pts), hepatocellular adenoma diagnosis (4 pts), undeterminate liver mass (2 pts), a liver mass of unknown origin in patients with a neoplastic history (3 pts). A diagnosis of focal nodular hyperplasia assumed by the imaging work-up was always histologically confirmed. All the patients underwent hepatic resection with no mortality. CONCLUSIONS: This report underlines the risk of hemorrhage or malignant transformation of hepatocellular adenoma that justifies a safety surgical resection. An imaging work-up in favor of focal nodular hyperplasia allows radiological observation.

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.

Evaluation of the role of human papillomavirus in oesophageal squamous cell carcinoma in Belgium.

OBJECTIVE: To evaluate the putative role of human papillomavirus (HPV) in the aetiology of oesophageal squamous cell carcinoma (OSCC) in Belgium. METHODS: The frequency of HPV infection was determined using HPV DNA PCRamplification with L1 consensus primers MY09-MY11, able to recognise about 40 different HPV types, on twenty-one formalin-fixed and paraffin-embedded oesophageal squamous cells carcinomas. Nineteen samples of histologically normal epithelium from the surgical margins of the OSCC specimens and five samples from normal oesophagus obtained at autopsy served as negative controls. RESULTS: We found only one HPV positive tumour (4.8%) out of the 21 OSCC cases. All the normal epithelium controls remained negative. CONCLUSIONS: Our data are in agreement with those previously published, suggesting that HPV infection only plays a minor role in the pathogenesis of oesophageal squamous cells carcinoma in West-European countries.

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.

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.

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.

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.

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.

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.