Intraoperative hepatic ultrasonography (IOUS) has been used to accurately identify and localize hepatic tumors as an adjunct to hepatic resection and for the detection of occult liver metastases ...during primary resection of other gastrointestinal carcinomas. The face validity of IOUS to identify more lesions than conventional diagnostic modalities and the content validity of IOUS to change the planned surgical management has been assessed in a blinded, prospective manner.
Sixty-two patients were studied at two institutions by one surgeon. IOUS was compared with computed tomography (CT) angioportography in 30 patients undergoing planned hepatic resection (19 metastatic, 11 primary) and with conventional hepatic ultrasonography (+/- venous enhanced CT scan) in 32 patients undergoing primary excision of gastrointestinal carcinomas.
Twenty of the 30 hepatic resections (67%) were changed or guided by IOUS as determined by the operating surgeon at the completion of the laparotomy. IOUS detected 26 more metastases (44%) in 10 of 19 patients (1 to 5 per patient). Two patients had preoperatively suspected metastases refuted by IOUS-guided biopsy. Eight of the 11 patients (73%) undergoing resection of primary carcinoma of the liver had the planned procedure changed or guided by IOUS. This included four hepatocellular carcinomas with more extensive involvement at the confluence of the hepatic veins and the inferior vena cava, necessitating resection with the aid of total vascular isolation. In 32 patients undergoing primary resection of gastrointestinal carcinomas, 5 patients (16%) had the stage of disease altered by IOUS when compared with conventional ultrasound (+/- venous enhanced CT scan).
The validity of IOUS is good. IOUS guided the intraoperative surgical management of two thirds of the patients undergoing hepatic resection when compared with CT angioportography. Intraoperative hepatic ultrasonography using a reproducible systematic approach can change the clinical management of patients undergoing hepatic resection for malignancy.
BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have ...substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been ...anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of greater use in cancer detection and of value in radioimmunotherapy of human cancer. We compared the pharmacokinetics, biodistribution, and immune responses of 131I-labeled CC49 and CC83 to 125I-labeled B72.3 by preoperatively coninjecting dual-labeled MAbs into 16 colorectal cancer patients. The imaging properties of radiolabeled CC49 and CC83 were also assessed. Pharmacokinetics of all three MAbs were identical, and there were no differences in the uptake of any of three MAbs in tumor and normal tissues. Maximum tumor uptake was 0.0041% of the injected dose/g for 125I-B72.3, 0.0024% for 131I-CC49, and 0.0029% for 131I-CC83. Radiolabeled CC49 and CC83 detected most known tumor sites on scintigrams without any clear advantage for either MAb. Nonspecific splenic and testicular uptake was frequently observed. Anti-idiotypic human anti-mouse antibody responses were seen more frequently with B72.3 than with CC49 or CC83. We conclude that higher affinity, radiolabeled anti-TAG-72 MAbs can detect colorectal cancer but do not penetrate these tumors more effectively than B72.3. Improvements in tumor detection and radioimmunotherapeutic strategies will likely require the administration of smaller fragments of MAb molecules or novel delivery systems rather than the continued development of higher affinity MAbs.
APC (Adenomatous polyposis coli) plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic ...adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process.
To elucidate the biological dysregulation underlying adenoma formation we examined global gene expression profiles of adenomas and corresponding normal mucosa from an FAP patient. Differential expression of the most significant gene identified in this study was further validated by mRNA in situ hybridization, reverse transcriptase PCR and Northern blotting in different sets of adenomas, tumours and cancer cell lines.
Eighty four genes were differentially expressed between all adenomas and corresponding normal mucosa, while only seven genes showed differential expression within the adenomas. The first group included pregnancy specific beta-1 glycoprotein 9 (PSG9) (p < 0.006). PSG9 is a member of the carcinoembryonic antigen (CEA)/PSG family and is produced at high levels during pregnancy, mainly by syncytiotrophoblasts. Further analysis of sporadic and familial colorectal cancer confirmed that PSG9 is ectopically upregulated in vivo by cancer cells. In total, deregulation of PSG9 mRNA was detected in 78% (14/18) of FAP adenomas and 75% (45/60) of sporadic colorectal cancer cases tested.
Detection of PSG9 expression in adenomas, and at higher levels in FAP cases, indicates that germline APC mutations and defects in Wnt signalling modulate PSG9 expression. Since PSG9 is not found in the non-pregnant adult except in association with cancer, and it appears to be an early molecular event associated with colorectal cancer monitoring of its expression may be useful as a biomarker for the early detection of this disease.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Unlike colorectal cancer, risk markers for adenocarcinoma of the small intestine (ASI) have not been identified. Because the demographic and pathological features of both of these diseases are ...similar, immunohistochemistry was performed using monoclonal antibodies for three colonic premalignant markers, Adnab-9 (recognizes a colonic adenoma epitope), CaCo3/61, and FBB2/29 (small intestine proteoglycans expressed ectopically in colonic neoplasms), in normal and neoplastic small intestinal epithelium, and the results were compared with normal controls. Adnab-9 was also examined in 20 familial adenomatous polyposis (FAP) patients, a population known to be at an increased risk for ASI. Immunohistochemistry in normal and neoplastic tissue (adenoma, adenocarcinoma) from 18 patients with primary adenocarcinoma of the small intestine was compared with normal small intestine from 10 nonneoplastic controls. Four of 10 (40%) cases of normal small intestinal epithelium from controls were mildly positive in less than 10% of crypts, versus strong staining (>50% of crypts) in 16 of 18 (89%) patients with adenocarcinoma, and in 17 of 20 (85%) patients with FAP (
P < .05). Adnab-9 predominantly stained Paneth cells as well as rare crypt and basal villous goblet cells. Adenomatous epithelium from the adenocarcinoma cases and adenomas from the FAP patients showed staining of Adnab-9 in 63% and 78% of cases, respectively. Only 17% of adenocarcinomas were positive for Adnab-9. In contrast, neither CaCo3/61 nor FBB2/29 showed any significant differences in the degree of staining in normal small intestinal epithelium in patients with adenocarcinoma compared with controls. Enhanced Adnab-9 staining in normal small intestinal epithelium from patients who harbor adenocarcinoma, and in FAP patients, supports its role as a risk marker of small intestinal neoplasia.
To assess the safety and efficacy of radiofrequency ablation (RFA) in the treatment of malignant neoplasms of the liver.
Sixty-seven patients received RFA for primary or secondary hepatic ...malignancies. Patients were followed prospectively with computed tomography (CT) scanning to assess for therapeutic response, disease progression and complications.
Eighty-eight lesions were treated, including 57 hepatocellular carcinomas, 28 metastases, 2 cholangiocarcinomas and 1 hepatic plasmacytoma. Mean tumour size was 2.7 cm (range 0.5-6.9 cm). A total of 101 ablations were performed (66 percutaneously, 35 intraoperatively). Over a mean follow-up period of 142 days, results were available for 85 lesions. Local tumour control was achieved for 61 (72%) lesions, but new distant lesions developed in 6 of these cases. Residual disease was present in 20 (23%) lesions, and 4 (5%) lesions developed local recurrence. There were 10 complications, including 1 death in a patient who developed a liver abscess and subsequently died from hepatic failure.
RFA is safe and effective in the treatment of hepatic malignancies. Local tumour control can be achieved in most cases; however, careful surveillance is important for detecting recurrent disease, as well as new lesions distant from the treated site.
Previous studies from this laboratory suggested that high gallbladder protein concentrations as well as excessive dehydration of bile might reduce the normal metastability of human gallbladder bile. ...This study attempted to identify persons in an early stage of stone formation, when there are crystals but no stones, and to determine the composition of bile under these conditions of reduced metastability. Two hundred twenty-seven patients were studied, 96 without gallstones. Twenty-three of 96 control patients had cholesterol crystals in their bile. Total protein concentration, total lipid concentration, and cholesterol saturation index were greater in control patients with crystals in bile. To determine whether or not cholesterol saturation index alone could account for the presence of crystals, control patients with cholesterol saturation index above the median value of 1.04 were studied. In this case there was no difference in cholesterol saturation index between the 19 crystal-positive (1.27) and 29 crystal-negative patients (1.26), but the difference in total protein and lipid concentrations persisted. Total protein and total lipid concentrations were even higher in crystal-positive sediments containing large numbers of crystals. Sludge seen by ultrasonography was more common in patients with crystal-positive sediments. High protein and lipid concentrations are associated with reduced metastability of bile.
NK cells lyse target cells without previous immune sensitization. A small subset of T cells also exhibits NK-like activity, which is distinct from TCR-mediated, MHC-restricted, and MHC-unrestricted ...cytotoxicity. We recently cloned a gene, NK-TR, which is postulated to be part of the NK target-recognition/triggering complex. To determine whether the NK-TR gene product is requisite for NK-like killing, stable antisense transfectants were generated by using a human T cell clone with NK-like activity. Two distinct antisense regions of the sequence were used to generate the transfectants alpha NK-TR and alpha Cyclo. Transfectants lost the ability to lyse NK-sensitive targets but did not lose lectin-mediated cytotoxic activity. This effect was not seen with the control vector transfectant cell line. The loss of NK-like activity by the antisense transfectant alpha NK-TR correlated with the specific decrease in endogenous NK-TR mRNA and protein. These results demonstrate the requirement for the NK-TR protein for NK-like killing. Moreover, the results have important implications for examining developmental relationship between T and NK cells and the possible roles for T cells with NK-like activity in vivo.
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