Improvement in systemic chemotherapy options for advanced cases of bilharzial bladder cancer

Bilharzial bladder cancer is a major health problem in Egypt, as well as some African and Asian countries it represents a distinct clinicopathologic disease. In order to investigate efficacy of chemotherapy in cases with advanced bilharizial bladder cancer as well as different clinicopathologic factors, that may impact response to chemotherapy, we conducted a phase III study, upon 58 patients, over the period from April 1999 to Dec. 2002. The 58 patients had pathologically proven bladder carcinoma on top of previous bilharzial cystitis presenting with either metastatic, inoperable, or recurrent disease. The 55 patient's evalvuable for response, 26 patients were randomized to receive single agent epidoxorubicin, claimed to be most active single agent in cases of bilharzial bladder cancer and the remaining 29 patients received the combination of epidoxorubicin with vincristine alternating with etoposide and ifosfamide. The clinicopathologic characteristics of the two groups were comparable, except for the higher frequency of grade 3 tumors in the combination chemotherapy group. Those who received single agent chemotherapy, had a response in only 4 cases response rate [15.38%] with only 2 cases achieving complete remission, those receiving combination chemotherapy had a response in 11 patients [response rate of 37.9%] with only 2 patients achieving complete responses. In terms of disease control rate [CR+PR+SD] epirubicin had a control rate of 46. 15%, with a mean TDP of 8 months and mean OS of 9 months, versus 62% for those receiving combination treatment with a mean TDP of 7 months and a mean OS. of 9.4 months. The 5 year actuarial PFS rate for patients who have achieved PR and CR in both treatment groups [15 patients] was 20.5%, SE = 5.8. Combination treatment group had a higher PFS of 36.2%, in contrast to 15.4% in the group receiving epidoxorubicin treatment, a difference that proved to be statistically significant [p=0.04]. Patients randomized to receive combination treatment had a higher 5 year overall survival rate of 37.9%, versus 25.5% in patient receiving epidoxorubicin treatment, however, this difference was not statistically significant [p=O.4]. Seventy six percent of patients receiving combination treatment expressed both MDR and p53 versus 33% and 50% respectively for those receiving single agent epidoxorubicin, yet such occurrence had no statistically significant correlation with response, but MOR affected OS and PFS for responding cases. Toxicity from treatment was in the form of vomiting, mucositis, diarrhea, leucopenia, anemia and were all comparable between both groups except for alopecia which was more prominent in those receiving single agent epidoxorubicin Among different clinicopathologic variables only the pathologic cell type seemed to affect response

Point mutation of p53 gene exon 7 as a new early diagnostic marker of hepatocellular carcinoma

Background: One of the characteristics of hepatocellular carcinoma [HCC] is the selective mutation resulting in serine substitution at codon 249 of the p53 tumor suppressor gene, and it has been identified as a "hotspot" mutation in hepatocellular carcinomas occurring in populations exposed to aflatoxins and with high prevalence of hepatitis B virus [HBV] and hepatitis C virus [HCV]. Objective: To evaluate whether this "hotspot" mutation could be detected in cell free DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis, and tried to determine the significance of the detection of this molecular biomarker

Subjects and Methods: Blood samples were collected from 105 subjects. Fourty two patients with hepatocellular carcinoma, 35 cirrhotic patients and 28 healthy control. DNA was extracted from the patient's plasma. The 249ser p53 mutation was detected by restriction digestion analysis after PCR amplification

Results: A total of 34 of the 105 subjects [32.4%] had p53 mutation, 22 from 42 subjects [52.4%] with hepatocellular carcinoma, 10 from 35 subjects [28.6%] with cirrhosis, and 2 from 28 subjects [7.1%] were healthy controls. The adjusted odds ratio [OR] for having mutation was 7.33 [95% confidence intervals [CI] 1.87-28.75] for HCC cases compared to controls which was extremly significant statistically [P <0.0001]. Eight out of the 34 positive mutation were HbsAg+ [23.5%] "5 from HCC and 3 from cirrhotic patients" while 17 out of 34 positive mutation were positive Anti-HCV [50%] "13 from HCC and 4 from cirrhotic patients"

Conclusion: These data show that the 249ser p53 mutation in plasma is strongly associated with HCC. We found this mutation was also detected in plasma DNA of cirrhotics and healthy controls but at a much lower frequency. We consider that these findings, together with the conventional methods of HCC diagnosis, will give more information in ealry diagnosis of HCC, and 249ser p53 mutation may be a new early diagnostic marker for HCC

Changing pattern in the epidemiology and diagnosis of colorectal carcinoma in Egypt

Colorectcd carcinoma [CRC] is one of the common tumors in the gastrointestinal tract. Patients usually presented late either due to the wide range of symptoms or the wide range of sensitivity of the diagnostic tools used in practice. The aim of this work was to 1] assess the age distribution pattern, residence, sex and the presenting symptoms of CRC among Egyptian patients. 2] evaluate the diagnostic value of double contrast barium enema [DCBE], conventional pelviabdominal ultrasonography [US] and spiral CT in detecting tumor lesions. 3] assess the value of preoperative spiral CT staging of CRC compared to laparotomy according to the TNM classification of the American Join Committee on Cancer [AJCC]. This descriptive hospital-based study comprised 62 Egyptian patients [35 males and 27 females] with CRC. They were diagnosed by colonoscopy and histopathology in the gastroenterology unit at Suez Canal University, during the interval between July 1997 and July 2000. We found that, about 40% of the patients were under the age of 40 years, 67.74% of them were from rural areas. Males were more affected than females [1.29:1]. The most common presenting symptoms were alteration in the bowel habits [67.74%], abdominal pain [53.23%] and bleeding per rectum [45.16%]. Cachexia was found in 25.8% of patients, despite that 72.58% of them were diagnosed after 6 months of their complaint. The sensitivity of DCBE in detecting CRC was higher than US [62.9% versus 35.5%]. Spiral CT was accurate in detecting the affected sites in all cases [100% sensitivity]. Furthermore, spiral CT was of great help in the preoperative staging of CRC [86.6% sensitivity and 78.9% total accuracy] compared to surgical staging

Evaluation of serum total bile acids in the diagnosis of hepatocellular carcinoma

Fasting total serum bile acids [FSBA] concentrations were measured in 140 cases of chronic liver diseases including 50 patients with liver cirrhosis, 40 patients with chronic hepatitis and 50 patients with hepatocellular carcinoma [HCC]. FSBA concentrations were significantly higher in patients with HCC than those with chronic hepatitis and cirrhosis and both were significantly higher than the controls [p<0.0001]. FSBA concentrations were not correlated to the size of the tumor, the Child Pugh grades, the histopathologic grades and most of the liver function tests. Using the receiver operative characteristic [ROC] and the differential positive rate [DPR] analysis, 30 pmol/l was the optimal cut-off value that differentiates patients with HCC from those with cirrhosis. At this level, the sensitivity, the specificity and the diagnostic accuracy were 42%, 98% and 70% respectively. AFP was found to be significantly increased in patients with HCC than those with chronic hepatitis and cirrhosis. The best cut-off value of AFP was 100 ng/ml, at which the sensitivity, the speci-ficity and diagnostic accuracy were 52%, 96% and 74% respectively. The simultaneous determination of AFP and total bile acids raised the sensitivity of the test to 76%. The area under the ROC curve for AFP and total bile acids was 0.764 and 0.744 respectively, the difference is non-significant. In conclusion, both AFP and total bile acids are good markers for HCC and their simultaneous determination may improve the detection of HCC in cirrhotic patients negative for AFP