Role of Ki-67 as a prognostic factor in gastrointestinal stromal tumors

AIM:To investigate primarily the prognostic value of Ki-67,as well as other parameters,in gastrointestinal stromal tumors(GISTs).METHODS:Ki-67,c-KIT,platelet-derived growth factor receptor-alpha(PDGFRα),smooth muscle actin(SMA),CD34,S100 were stained for immunohistochemistry which was performed on formalin-fixed,paraffinembeded sections on representative block from each case.Proliferation index counted by Ki-67 antibody was calculated as a number of positive nuclear reaction over 100 cells.Immunoreactivity for c-KIT and PDGFRα was evaluated semiquantitatively(weak,intermediate,strong) and for c-KIT type of reactivity was analyzed(cytoplasmic,membrane and "dot-like" staining).Immunoreactivity for SMA,CD34 and S100 were was evaluated as positive or negative antigen expression.Pathologic parameters investigated in this study included tumor size,cell type(pure spindle,pured epitheloid mixed spindle and epitheloid),mitotic count,hemorrhage,necrosis,mucosal ulceration.Clinical data included age,gender,primary tumor location and spread of disease.χ 2 test and Student's t-test were used for comparisons of baseline characteristics.The Cox's proportional hazard model was used for univariable and multivariable analyses.Survival rates were calculated by Kaplan-Meier method and statistical significance was determined by the log-rank test.RESULTS:According to the stage of disease,there were 36 patients with localized disease,29 patients with initially localized disease but with its recurrence in the period of follow up,and finally,35 patients had metastatic disease from the very beginning of disease.Tumor originated most commonly in the stomach(41%),small intestine was the second most common location(36%).The mean size of primary tumors was 6.5 cm.The mean duration of follow-up was 60 mo.Multiple parameters were analyzed for their effect on overall survival,but no one reached statistical significance(P = 0.06).Analysis of time to progression/relapse in initially localized disease(univariate analysis),tumor size,mitotic count,Ki-67 and type of d-KIT distribution(cytoplasmic vs membrane/"dot-like") showed statistically significant correlation.In multivariate analysis in the group of patients with localized disease,there were only 2 parameters that have impact on relapse,Ki-67 and SMA(P < 0.0001 and P < 0.034,respectively).Furthermore,Ki-67 was analyzed in localized diseasevs localized with recurrence and metastatic disease.It was shown that there is a strict difference between these 2 groups of patients(median value was 2.5 for localized disease vs 10.0 for recurrent/metastatic disease,P < 0.0001).It was also shown that the cut-off value which is still statistically significant in terms of relapse on the level of 6%.The curves for survival on that cut-off level are significantly different(P < 0.04,Cox F).CONCLUSION:Ki-67 presents a significant prognostic factor for GIST recurrence which could be of great importance in evaluating malignant potential of disease.

Gardner's syndrome:Genetic testing and colonoscopy are indicated in adolescents and young adults with cranial osteomas:A case report

We present a case of a 25-year-old female with diagnosed familial adenomatous polyposis and elevated carcinoembryonic antigen with negative family history. The suspicion of Gardner's syndrome was raised because extirpation of an osteoma of the left temporo-occipital region was made 10 years ago. Restorative procto-colectomy and ileal pouch anal anastomosis was made but histology delineated adenocarcinoma of the rectum (Dukes C stage). We conclude that cranial osteomas often precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome and such patients should be evaluated with genetic testing followed by colonoscopy if results are positive to prevent the development of colorectal carcinoma. If the diagnosis is positive all family members should be evaluated for familial adenomatous polyposis.

Colonic duplication in an adult who presented with chronic constipation attributed to hypothyroidism

Gastrointestinal duplications are an uncommon congenital abnormality that manifest before the age of two in 80% of cases. Ileal duplication is the most common while colonic duplication, either cystic or tubular, occurs in 10%-15% of cases and remains asymptomatic and undiagnosed in most cases. Mostly occurring in pediatric patients, colonic duplication is encountered in adults in only a few cases. The most common clinical manifestations are abdominal pain and intestinal obstruction. Rarely, duplications present with signs of acute abdomen or acute bleeding. This study reports a case of colonic duplication in an adult who presented with chronic constipation. Complete diagnostic workup was made on several occasions during the previous eight year period, but no pathology was found and chronic constipation was attributed to hypothyroidism caused by long standing Hashimoto thyroiditis. Nultislice CT, performed because of abdominal distension, defined colonic pathology but the definite diagnosis of duplication of the transversal colon was made at operation. The cystic duplication and the adjacent part of the ascending and transversal colon were excised enblock. This study implies that colonic duplication, though uncommon, should be included in the differential diagnosis of chronic constipation even when precipitating factors for constipation, such as hypothyroidism are present.

Endoscopic ultrasound elastography strain histograms in the evaluation of patients with pancreatic masses

AIM: To investigate the accuracy of the strain histogram endoscopic ultrasound(EUS)-based method for the diagnostic differentiation of patients with pancreatic masses. METHODS: In a prospective single center study, 149 patients were analyzed, 105 with pancreatic masses and 44 controls. Elastography images were recorded using commercially available ultrasound equipment in combination with EUS linear probes. Strain histograms(SHs) were calculated by machine integrated software in regions of interest and mean values of the strain histograms were expressed as Mode 1(over the mass) and Mode 2(over an adjacent part of pancreatic tissue, representing the reference area). The ratio between Mode 2 and Mode 1 was calculated later, representing a new variable, the strain histogram ratio. After the final diagnosis was established, two groups of patients were formed: a pancreatic cancer group with positive cytology achieved by fine needle aspiration puncture or histology after surgery(58 patients), and a massforming pancreatitis group with negative cytology and follow-up after 3 and 6 mo(47 patients). All statistical analyses were conducted in SPSS 14.0(SPSS Inc., Chicago, IL, United States).RESULTS: Results were obtained with software for strain histograms with reversed hue scale(0 represents the hardest tissue structure and 255 the softest). Based on the receiver operating characteristics(ROC) curve coordinates, the cut-off point for Mode 1 was set at the value of 86. Values under the cut-off point indicated the presence of pancreatic malignancy. Mode 1 reached 100% sensitivity and 45% specificity with overall accuracy of 66%(95%CI: 61%-66%) in detection of pancreatic malignant tumors among the patients with pancreatic masses. The positive and negative predictive values were 54% and 100%, respectively. The cut-off for the new calculated variable, the SH ratio, was set at the value 1.153 based on the ROC curve coordinates. Values equal or above the cut-off value were indicative of pancreatic malignancy. The SH ratio reached 98% sensitivity, 50% specificity and an overall accuracy of 69%(95%CI: 63%-70%). The positive and negative predictive values were 92% and 100%, respectively.CONCLUSION: SH showed high sensitivity in pancreatic malignant tumor detection but disappointingly low specificity. Slight improvements in specificity and accuracy were achieved using the SH ratio.

Pentadecapeptide BPC 157 and the central nervous system

We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157,three very recent demonstrations that may be essential in the gut-brain and braingut axis operation,and therapy application in the central nervous system disorders,in particular.Firstly,given in the reperfusion,BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke,sustained brain neuronal damages were resolved in rats as well as disturbed memory,locomotion,and coordination.This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats.Secondly,there are L-NG-nitro arginine methyl ester(L-NAME)-and haloperidol-induced catalepsy as well as the rat acute and chronic models of 'positivelike' schizophrenia symptoms,that BPC 157 counteracted,and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine(dopamine agents application),MK-801(non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration(to induce sensitivity).Thirdly,after rat spinal cord compression,there were advanced healing and functional recovery(counteracted tail paralysis).Likewise,in BPC 157 therapy,there is specific support for each of these topics:counteracted encephalopathies;alleviated vascular occlusion disturbances(stroke);counteracted dopamine disturbances(dopamine receptors blockade,receptors super sensitivity development,or receptor activation,over-release,nigrostriatal damage,vesicles depletion),and nitric oxide-system disturbances("L-NAME non-responsive,L-arginine responsive," and "L-NAME responsive,L-arginine responsive")(schizophrenia therapy);inflammation reduction,nerve recovery in addition to alleviated hemostasis and vessels function after compression(spinal cord injury therapy).Thus,these disturbances may be all resolved within the same agent's beneficial activity,i.e.,the stable gastric pentadecapeptide BPC 157.