Clinical and serological outcomes with different surgical approaches for human hepatic hydatidosis.

INTRODUCTION: Hydatidosis is the result of infection with the larval stages of some species of the genus Echinococcus. Treatment approaches for hydatid cysts include the use of albendazole, surgery, and/or medico-surgical procedures. The choice of the therapeutic surgical approach depends on the cyst number and localization, surgeon expertise, and presence of complications. The present study aimed to compare the outcomes of the following therapeutic approaches for the treatment of hepatic hydatid cysts: pericystectomy; the puncture, aspiration, injection, and reaspiration (PAIR) technique; and the PAIR technique followed by deroofing, evacuation of cysts, and omentoplasty. METHODS: The 54 patients were divided into 3 groups: Group I (14 patients) who underwent pericystectomy, Group II (23 patients) who underwent the PAIR technique, and Group III (17 patients) who underwent the PAIR technique followed by deroofing and omentoplasty. The diagnosis of hydatid cysts was based on serological testing using enzyme-linked immunosorbent assay, abdominal ultrasound, and parasitological examination of the cyst contents. Morbidity, mortality, length of hospital stay, recurrence, and postoperative complications were evaluated. RESULTS: Postoperative bleeding, infection, and recurrence were reported in Groups I and II; Group III did not experience postoperative infection and had shorter hospital stays. Recurrence and postoperative complications did not occur in Group III. CONCLUSIONS: The partial surgical procedure with deroofing, evacuation of the cysts, and omentoplasty, as performed in the present study, is recommended as a safe and effective method for elimination of the entire parasite with minimal possibility for intra-peritoneal spillage.

Clinical and serological outcomes with different surgical approaches for human hepatic hydatidosis

ABSTRACTINTRODUCTION:Hydatidosis is the result of infection with the larval stages of some species of the genus Echinococcus. Treatment approaches for hydatid cysts include the use of albendazole, surgery, and/or medico-surgical procedures. The choice of the therapeutic surgical approach depends on the cyst number and localization, surgeon expertise, and presence of complications. The present study aimed to compare the outcomes of the following therapeutic approaches for the treatment of hepatic hydatid cysts: pericystectomy; the puncture, aspiration, injection, and reaspiration (PAIR) technique; and the PAIR technique followed by deroofing, evacuation of cysts, and omentoplasty.METHODS:The 54 patients were divided into 3 groups: Group I (14 patients) who underwent pericystectomy, Group II (23 patients) who underwent the PAIR technique, and Group III (17 patients) who underwent the PAIR technique followed by deroofing and omentoplasty. The diagnosis of hydatid cysts was based on serological testing using enzyme-linked immunosorbent assay, abdominal ultrasound, and parasitological examination of the cyst contents. Morbidity, mortality, length of hospital stay, recurrence, and postoperative complications were evaluated.RESULTS:Postoperative bleeding, infection, and recurrence were reported in Groups I and II; Group III did not experience postoperative infection and had shorter hospital stays. Recurrence and postoperative complications did not occur in Group III.CONCLUSIONS:The partial surgical procedure with deroofing, evacuation of the cysts, and omentoplasty, as performed in the present study, is recommended as a safe and effective method for elimination of the entire parasite with minimal possibility for intra-peritoneal spillage.

Loss of p15INK4b expression in colorectal cancer is linked to ethnic origin.

Colorectal cancers remain to be a common cause of cancer-related death. Early-onset cases as well as those of various ethnic origins have aggressive clinical features, the basis of which requires further exploration. The aim of this work was to examine the expression patterns of p15INK4b and SMAD4 in colorectal carcinoma of different ethnic origins. Fifty-five sporadic colorectal carcinoma of Egyptian origin, 25 of which were early onset, and 54 cancers of Finnish origin were immunohistochemically stained with antibodies against p15INK4b and SMAD4 proteins. Data were compared to the methylation status of the p15INK4b gene promotor. p15INK4b was totally lost or deficient (lost in ≥ 50% of tumor cell) in 47/55 (85%) tumors of Egyptian origin as compared to 6/50 (12%) tumors of Finnish origin (p=7e-15). In the Egyptian cases with p15INK4b loss and available p15INK4b promotor methylation status, 89% of cases which lost p15INK4b expression were associated with p15INK4b gene promotor hypermethylation. SMAD4 was lost or deficient in 25/54 (46%) tumors of Egyptian origin and 28/48 (58%) tumors of Finnish origin. 22/54 (41%) Egyptian tumors showed combined loss/deficiency of both p15INK4b and SMAD4, while p15INK4b was selectively lost/deficient with positive SMAD4 expression in 24/54 (44%) tumors. Loss of p15INK4b was associated with older age at presentation (>50 years) in the Egyptian tumors (p=0.04). These data show for the first time that p15INK4b loss of expression marks a subset of colorectal cancers and ethnic origin may play a role in this selection. In a substantial number of cases, the loss was independent of SMAD4 but rather associated with p15INK4b gene promotor hypermethylation and old age which could be related to different environmental exposures.

Distinct genetic and epigenetic signatures of colorectal cancers according to ethnic origin.

BACKGROUND: The outcome of colorectal cancer varies depending on ethnic origin. Egyptian colorectal carcinoma is surprisingly young-age disease with high proportion of rectal and advanced stage cancers. METHODS: We characterized 69 sporadic Egyptian colorectal cancers for promoter methylation at 24 tumor suppressor genes, microsatellite instability, and expression of mismatch repair, p53, and ß-catenin proteins. Data were compared with 80 Western colorectal carcinoma of sporadic and familial origin from Finland. RESULTS: Egyptian colorectal carcinomas showed significantly higher methylation of the microsatellite stable (MSS) tumors as reflected by the average number of methylated genes per case (P = 0.00002) and tumor suppressor gene methylator phenotype (TSGMP), defined here as methylation of ≥ 5 genes, (P = 0.0001) compared with the sporadic Western cancers. The TSGMP was associated with advanced stage in the Egyptian cancers (P = 0.0016). Four genes were differentially methylated between Egyptian and Western cases, of which the association of CDKN2B/p15 methylation with Egyptian origin was outstanding (P = 4.83 E-10). Egyptian carcinoma also showed significantly lower frequency of nuclear ß-catenin localization than the sporadic Western cancers (P = 0.00006) but similar to that of the familial Western subset designated as familial colorectal cancer type X. CONCLUSIONS: We show novel pathway in colon carcinogenesis marked by high methylation of MSS cancers, remarkable CDKN2B/p15 methylation, and low frequency of Wnt signaling activation. IMPACT: Our findings highlight the possible effect of environmental exposures in carcinogenesis through DNA methylation and should have applications in prevention, molecular diagnosis, prognosis, and treatment.

Assessment of Her-2/neu gene amplification status in breast carcinoma with equivocal 2+ Her-2/neu immunostaining.

BACKGROUND AND PURPOSE: Amplification of Her-2/neu gene occurs in 25-30% of breast carcinomas. FDA approved trastuzumab (Herceptin) is effective only in tumors having the gene amplification. Immunohistochemistry (IHC) for Her-2/neu protein is widely used but false positive and false negative results exist. Fluorescence in-situ hybridization (FISH) has both excellent sensitivity and specificity in detecting Her-2/neu amplification. Comparative studies have shown discordant results in proportion of cases with equivocal 2+ immunostain. This study is thus conducted to ascertain the frequency of Her-2/neu gene amplification by FISH in breast carcinoma specified as score 2+ by IHC and to correlate these findings with parameters of prognosis in breast cancer. METHODS: From October 2008 till May 2010 all paraffin blocks from cases with invasive breast carcinoma which were scored as 2+ by IHC were eligible for the study, there were 50 cases. Immunohistochemical evaluation of Her-2/neu was performed using the HercepTest. All cases were immunohistochemically evaluated for ER and PR. FISH was performed using FDA approved Path-Vysion Her-2/neu/CEP 17 dual color probe. RESULTS: Nine cases (18%) out of 50 cases scored as Her-2/neu 2+ by IHC showed true gene amplification with a median value of scoring ratio 4.28 ranging from 2.37 to 13.26. Another two cases showed low level of amplification but when corrected for Her-2/neu/CEP ratio they did not show true amplification as they were associated with polysomy 17. With the exception of tumor size, neither patient's age, histologic grade nor lymph node status were correlated with Her-2/neu gene amplification. Significant inverse correlation existed between Her-2/neu gene amplification and ER (P=0.01), PR status (P<0.001). CONCLUSION: Even though FISH is a more complex and expensive procedure, it should be considered the method of choice for assessment of Her-2/neu gene status especially for equivocal cases by IHC that are not accompanied by true gene amplification in the majority of breast carcinoma cases.

Somatic FGF9 mutations in colorectal and endometrial carcinomas associated with membranous beta-catenin.

We previously described striking molecular features including high frequency of membranous beta-catenin in subsets of familial colon cancers with as yet unknown predisposition. We hypothesized that such tumors might carry mutations in Wnt/beta-catenin target genes. Fibroblast growth factor 9 (FGF9) was an attractive target, as it maps to a common area of loss of heterozygosity (LOH) in colorectal carcinomas on 13q12.11. Here, we report, for the first time, the occurrence of FGF9 mutations in human cancers. We found a total of six distinct FGF9 mutations including one frameshift, four missense, and one nonsense, in 10 (six colorectal and four endometrial) out of 203 tumors and cell lines. The frameshift mutation was detected in five different tumors. Mapping of these mutations onto the crystal structure of FGF9 predicted that they should all lead to loss of function albeit through variable mechanisms. The p.R173K mutation should diminish ligand affinity for heparin/heparan sulfate, the p.V192M, p.D203G, and p.L188YfsX18 (FGF9(Delta205-208)) mutations should negatively impact ligand's interaction with receptor, while p.G84E and p.E142X (FGF9(Delta142-208)) mutations should interfere with ligand folding. Consistent with these structural predictions, the p.V192M, p.D203G, and p.L188YfsX18 (FGF9(Delta205-208)) mutations impaired the ability of ligand to activate mitogen-activated protein kinase (MAPK) cascade in cultured cells expressing FGF receptors. LOH was observed in seven out of nine FGF9 mutant tumors, supporting the predicted loss of function. Interestingly, eight out of 10 (80%) of the FGF9 mutant tumors showed normal membranous beta-catenin expression and the absence of mutation in the beta-catenin gene (CTNNB1). These data suggest that FGF9 plays a role in colorectal and endometrial carcinogenesis.