The plasminogen system in microdissected colonic mucosa distant from an isolated adenoma.

In the colon, the urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitors, PAI-1 and PAI-2, are implicated in the transition from mucosa to adenoma and tumour progression. However, expression in the mucosa adjacent, or distant, to an adenoma has not yet been investigated. Three biopsies from mucosae adjacent (20 cm, ipsilateral) and distant (contralateral) to an isolated tubular adenoma were analysed in 14 patients and 8 controls. Laser microdissection isolated stromal and epithelial crypt components, and quantitative RT-PCR analyses of uPA, uPAR, PAI-1 and PAI-2 mRNA levels were performed. Among controls, no significant differences in the markers were noted. With left colon isolated tubular adenoma, uPA, uPAR, and PAI-2 mRNA levels were significantly increased in the adjacent mucosal stroma compared to epithelial crypt levels (p < 0.05). In right colon adenoma, the mRNA levels of these 3 molecular markers were significantly increased only in the adjacent mucosal stromal samples (p < 0.05). Isolated tubular adenoma in the colon increases significantly the mRNA levels of 3 proteolysis-associated molecular markers in the stromal, but not in the epithelial, components of adjacent mucosa. These results suggest the presence of regional and dynamic interactions in apparently non-involved mucosae.

Molecular pathology of colorectal cancer.

Colorectal cancer (CRC) is one of the most intensively studied cancer types, partly because of its high prevalence but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently (sessile) serrated adenomas, which can be detected endoscopically and removed. The morphological steps in the adenoma-carcinoma sequence have been elucidated at a molecular level, which has been facilitated by identification of the genes responsible for familial intestinal cancer. However, apart from early detection of familial forms of CRC and its use in genetic counseling, until recently such detailed molecular knowledge has had little impact on clinical management of the disease. This has dramatically changed in the last decade. With drugs specifically targeting the epidermal growth factor receptor (EGFR) having been shown effective in CRC, mechanisms responsible for resistance have been explored. The finding that KRAS mutated cancers do not respond to anti-EGFR treatment has had a profound impact on clinical management and on molecular diagnostics of CRC. Additional genetic tests for mutations in NRAS, BRAF and PIK3CA contribute to determining who to treat, and others will follow. New therapies effective in patients with advanced CRC are under investigation. Remaining burning questions for optimal management are which patients will relapse after resection of the primary tumor and which patients will respond to the standard 5FU-oxaliplatin adjuvant treatment regimen. Predictive tests to address these issues are eagerly awaited. New classifications of CRC, based on molecular parameters, are emerging, and we will be confronted with new subtypes of CRC, for which the definition is based on combinations of gene expression patterns, chromosomal alterations, gene mutations and epigenetic characteristics. This will be instrumental in designing new approaches for therapy but will also be translated into molecular diagnostics. Both will contribute to improved clinical management of CRC.

Appropriateness of colonoscopy in Europe (EPAGE II). Surveillance after polypectomy and after resection of colorectal cancer.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for surveillance after polypectomy and after curative-intent resection of colorectal cancer (CRC), and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of surveillance colonoscopy after polypectomy and after resection of CRC was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Most CRCs arise from adenomatous polyps. The characteristics of removed polyps, especially the distinction between low-risk adenomas (1 or 2, small [< 1 cm], tubular, no high-grade dysplasia) vs. high-risk adenomas (large [> or = 1 cm], multiple [> 3], high-grade dysplasia or villous features), have an impact on advanced adenoma recurrence. Most guidelines recommend a 3-year follow-up colonoscopy for high-risk adenomas and a 5-year colonoscopy for low-risk adenomas. Despite the lack of evidence to support or refute any survival benefit for follow-up colonoscopy after curative-intent CRC resection, surveillance colonoscopy is recommended by most guidelines. The timing of the first surveillance colonoscopy differs. The expert panel considered that 56 % of the clinical indications for colonoscopy for surveillance after polypectomy were appropriate. For surveillance after CRC resection, it considered colonoscopy appropriate 1 year after resection. CONCLUSIONS: Colonoscopy is recommended as a first-choice procedure for surveillance after polypectomy by all published guidelines and by the EPAGE II criteria. Despite the limitations of the published studies, colonoscopy is also recommended by most of the guidelines and by EPAGE II criteria for surveillance after curative-intent CRC resection.

Morbiditat postoperatòria en pacients intervinguts d’un adenoma hipofisari: comparació dels tumors no funcionants i dels secretors d’hormona de creixement i corticotropa

La neurocirurgia és el tractament definitiu més utilitzat pels tumors hipofisaris. Objectiu: valorar les complicacions postquirúrgiques immediates(1º mes) i durant el 1º any dels adenomes hipofisaris secretors de GH, ACTH i no funcionants(NF) operats des del 2001. Metodologia: estudi observacional restrospectiu de 94 pacients (39H, 55D) amb edat a la cirurgia de 46,9±15,5 anys, intervinguts pels 2 mateixos neurocirurgians. Resultats: 40 pacients tenen alguna complicació immediata(42,5% dels NF, 37% GH i 48,5% ACTH) sense diferències en la freqüència de complicacions entre els 3 grups. Les complicacions més freqüents són: diabetis insípida transitòria(23,4%), fístula LCR(6,7%), sinusitis i meningitis(2,2%). Els secretors d'ACTH tenen una tendència a tenir més DI transitòria i sinusitis respecte els NF(p=0,071), mentre que els NF tendeixen a presentar més fístules LCR, meningitis i convulsions(p=0,08). En els GH, existeix major incidència de fístules LCR comparat amb els ACTH(p&0,05), sense diferències amb els NF. 10 pacients tenen complicacions al 1º any postquirúrgic(7,5% dels NF, 11,1% GH i 14,8% ACTH), destacant major incidència d'artromiàlgies i síndrome del túnel carpià en els ACTH comparat amb els altres 2 grups (p&0,05). Les variables més importants quan fem una predicció d'aparició de complicacions són: tipus de cirurgia utilitzada (més a craniotomies que als abordatges transesfenoidals) i presència d'extensió extraselar tumoral, sense ser significatiu(p=0,091). Conclusions: malgrat que els tumors d'ACTH són majoritàriament microdenomes(77,7%), i es presenten en pacients més joves, tendeixen a associar-se a major nombre de complicacions immediates i durant el primer any en comparació amb els NF i GH(97,5%, 81,4% macroadenomes respectivament).

Transformation of a microprolactinoma into a mixed growth hormone and prolactin-secreting pituitary adenoma.

Combined prolactin (PRL) and growth hormone (GH) secretion by a single pituitary tumor can occur in approximately 5% of cases. However, in all previously reported patients, combined secretion of both hormones was present at the time of diagnosis. Here we describe a patient initially diagnosed with a pure prolactin-secreting microadenoma, who experienced the progressive apparition of symptomatic autonomous GH secretion while on intermittent long term dopamine agonist therapy. She was operated on, and immunohistochemical analysis of tumor tissue confirmed the diagnosis of pituitary adenoma with uniform co-staining of all cells for both GH and PRL. This patient represents the first documented occurrence of asynchronous development of combined GH and PRL secretion in a pituitary adenoma. Although pathogenic mechanisms implicated remain largely speculative, it emphasizes the need for long term hormonal follow up of patients harboring prolactinomas.

Hyperaldostéronisme primaire sur adénome ou hyperplasie de la surrénale: opérer ou non [Primary hyperaldosteronism with adrenal adenoma or hyperplasia: surgical case or not?].

Primary hyperaldosteronism is one of the most frequent causes of secondary hypertension. Cardiovascular morbimortality is higher than in essential hypertonic and justifies diagnostic and specific treatment of this pathology. Therapeutic choice depends of health and desire of the patient. It is either medical with mineralocorticoid receptor antagonists, or surgical through adrenalectomy. In this case, a pre-surgery exam including a radiologic examination and a venous adrenal catheterism has to be done. Surgery allows a normalisation of kaliema and a blood pressure decrease in 50 to 88% of the patients. Beyond them, 30% are able to stop entirely their medication. Both therapeutic choices decrease cardiovascular risks equally if blood pressure is controlled.

Adénome pléomorphe simulant une dacryoadénite [Pleomorphic adenoma mimicking dacryoadenitis].

A 56-year-old female patient displayed an increased volume of her left lacrimal gland with pain and inflammation. On CT scan, a hyperdense lacrimal mass was found in the left lacrimal fossa. Observation was the first course, for no steroid therapy could be applied because of evolving digestive ulcers. After 9 months of observation, the gland was surgically removed en bloc through a wide anterolateral approach. Pathological analysis of the gland showed a pleomorphic adenoma. This case illustrates the advantage of a wide surgical approach in treating lacrimal gland tumors, in order to avoid or limit the risk of recurrence.

Changes of the mucosal N3 and N6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.

Adenocarcinome au sein d'un adenome pleomorphe de la glande lacrymale. A propos d'un cas. [Adenocarcinoma in a pleomorphic adenoma of the lacrimal gland: a case study]

PURPOSE: To report a patient with an adenocarcinoma in a pleomorphic adenoma of the lacrimal gland. Adenocarcinoma constitutes a distinct group of epithelial malignancies of the lacrimal gland. METHODS: The clinical presentation, workup, surgical approach, and pathological findings were reviewed. RESULTS: A 56-year-old man presented with a 3-month history of a lacrimal fossa mass. This patient presented a painless mass in the upper outer eyelid with significant displacement of the globe. The tumor was localized to the lacrimal gland. Radiological investigations showed a round, well-defined lesion in the fossa of the lacrimal gland. We performed a lateral orbitotomy; en bloc resection was accomplished. The final specimen showed an adenocarcinoma in a pleomorphic adenoma. No recurrences were detected during follow-up. CONCLUSION: Although adenocarcinoma has rarely been reported in association with a pleomorphic adenoma of the lacrimal gland, this combination can exist. If the malignant tumor is limited in the pleomorphic adenoma, the prognosis appears to be better than in cases of local extension. Adjuvant therapy, radiation or others, are not useful.

Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.

Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE(2)-induced intestinal carcinogenesis are unclear. Here we report that PGE(2) indirectly transactivates PPARdelta through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE(2) treatment of Apc(min) mice dramatically increased intestinal adenoma burden, which was negated in Apc(min) mice lacking PPARdelta. We demonstrate that PPARdelta is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.

Intestinal microbiota in the adenoma progression to colorectal cancer: a cross-sectional study

Background: Colorectal cancer is a major health problem worldwide and many efforts have been done to delineate risk factors and develop screening strategies to reduce its incidence and mortality. Colorectal adenomas have been clearly considered preneoplastic lesions due to their potential malignant transformation via the adenoma-carcinoma sequence. Over the last years, intestinal microbiota has been studied in several diseases and it has been hypothesized that colonic microbiota could influence colorectal cancer pathogenesisObjective: The goal of this study is to analyse whether there is an association between the fecal microbiota profiling and the presence and progression of colorectal adenomas, detected in population undergoing colonoscopy, to better understand the role of intestinal microbiota in colorectal carcinogenesisDesign: A cross-sectional study in the Gastroenterology Department at Hospital Universitari Doctor Josep Trueta in Girona, in a period of time of two yearsParticipants: General population undergoing screening or diagnostic colonoscopy in the Digestive Endoscopy UnitOutcomes: Identification and characterization of intestinal microbiota in stool samples from healthy patients and patients with low and high risk colorectal adenomas

Adenoma viloso da ampola de Vater

The aim of this paper is to present a case of a 37-year-old female patient with a benign tumor of the Ampulla of Vater and a brief review of the literature. The patient presented with progressive obstructive jaundice and weigth loss due to the presence of two adenomas of the second portion of duodenum. Laboratory tests confirmed the presence of obstruction of the biliary tree. Ultrasound and CT scan of the abdomen revealed bile duct dilatation. ERCP showed a tumor at the site of the Ampulla of Vater. The biopsies revealed tubular adenoma. She was submitted to local resection of the tumors and sphincteroplasty, since the frozen biopsy at the time of surgery showed no malignancy. During the post-operative follow-up she presented recurrence of symptoms. An upper GI endoscopy revealed a tumor at the Ampulla of Vater. She was then submitted to Whipple procedure with an uneventful recovery.

Síndrome de conn causada por adenoma de adrenal-tratamento por videolaparoscopia

The authors present a case-report a 43 years old, female patient presenting with an eight-year history of hypertension caused by an adrenal adenoma. Hypokalemia and supressed plasma renina confirmed the diagnosis of primary hyperaldosteronism. An abdominal computed tomography revealed a right adrenal mass. The patient was successfully treated laparoscopically. The histopathological diagnosis was adenoma. The patient had normal blood pressure within three months.