A trial to assess the efficacy of glutamic acid in prevention of vincristine-induced neurotoxicity in pediatric malignancies: a pilot study

Vincristine is considered as a backbone of therapy in the induction and consolidation phases of pediatric malignancies. Neurotoxicity is a principal side effect of its use. This study is a randomized single-blinded placebo-controlled clinical trial to evaluate the role of glutamic acid in ameliorating neurotoxicity in pediatric patients with hematologic and solid tumors receiving vincristine during induction course. Fifty-four patients in the glutamic acid group received glutamic acid 1.5 grams daily orally in 3 divided doses during the 4-week induction with vincristine in a dose of 1.5 mg/m2 IV weekly. Placebo group (40 patients) received oral placebo 3 times daily in the same way as the glutamic acid group. The onset of neurotoxicity was significantly earlier in placebo group than in glutamic acid group regarding tendon Achilles reflex, Patellar reflex, parasthesia, and increased frequency of constipation. This was statistically significant mostly in third and fourth visits, no severe cases of strength and mental alteration side effects in both groups. Glutamic acid was well tolerated with no gastrointestinal side effects in patients. This study suggests that the coadministration of oral glutamic acid with repetitive intravenous bolus injections of vincristine resulted in a reduction of its neurotoxicity.     

Effects of proximal and distal ends of double-J ureteral stent position on postprocedural symptoms and quality of life: a randomized clinical trial

PURPOSE: To evaluate the effect of the position of the proximal and distal ends of Double-J ureteral stents on postprocedural flank pain, lower urinary-tract symptoms, and quality of life. PATIENTS AND METHODS: The study included 120 patients who required unilateral Double-J ureteral stents for various indications. They were randomized into two equal groups. Group 1 had longer stents, with the proximal end in the upper calix and the distal end crossing the midline of the bladder. Group 2 had proper stent length with the proximal end in the pelvis and the lower end just beyond the vesicoureteral junction. Patients answered a questionnaire regarding flank pain, dysuria, and urgency as well as quality of life after 1 week of stenting. RESULTS: Forty patients (67%) of group 1 and 43 (72%) of group 2 had mild flank pain, especially during urination. There was no significant difference in the degree of flank pain in the two groups. Moderate to severe dysuria was reported by 53 patients (88%) in group 1 and 11 patients (18%) in group 2 (P < 0.001). Moderate to severe urgency was reported by 48 patients (80%) in group 1 and in 14 (23%) in group 2 (P < 0.001). A worse quality of life was reported by patients in group 1, among whom moderate to severe bother was noted by 51 (85%) compared with group 2, in which moderate to severe bother was reported by only 13 patients (22%) (P < 0.001). CONCLUSION: Ureteral stents are associated with flank pain and lower urinary-tract symptoms. The flank pain was not affected by the length of stent. Urgency and dysuria as well as a worse quality of life were significantly more common in the patients who had longer stents.     

Novel Thiophenes,Thienopyrimidines, and Triazolothienopyrimidines for the Evaluation of Anticancer and Augmentation Effects of γ‐Radiation

New derivatives of thiophenes 2 , 12 , iminoaminothieno[2,3‐d]pyrimidines 3 , 5 , and 6 , triazolothieno[2,3‐d]pyrimidines 8–11 , pyrazolo‐ and triazinothieno[2,3‐d]pyrimidines 4 , 7 , respectively, have been prepared by different synthetic procedures. Structure elucidation of the newly synthesized compounds was carried out via elemental analyses and spectral data. The antitumor activity of compounds 2 , 3 , and 9–12 was evaluated against in‐vitro cell lines (HEPG‐2 and MCF‐7). Compounds 2 , 3 , 10 , 11 , and 12 showed significant in‐vitro cytotoxic activity against hepatocellular carcinoma (HEPG‐2) compared to the reference drug Doxorubicin. Compound 2 showed significant in‐vitro cytotoxic activity against breast cancer (MCF‐7) cells compared to the reference drug Doxorubicin. The augmenting effect of γ‐radiation was assessed; here, compounds 2 , 3 , 10 , and 11 showed the most potent in‐vitro anticancer activity.     

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy,with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Background The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT).Methods 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed.Results 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017).Conclusion No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.Subject terms: Breast cancer, Breast cancer     

Association between Level of Tumor Markers and Development of VTE in Patients with Pancreatic,Colorectal and Ovarian Ca: Retrospective Case- Control Study in Two Community Hospitals

The risk of venous thromboembolism (VTE) is increased in patients with cancer. However, the role of tumor markers as potential indicators of increased risk of VTE is still undetermined. In this retrospective observational case control study, levels of the tumor markers CEA, CA 19–9 and CA 125 in patients with colorectal, pancreatic, and ovarian cancer respectively, who were admitted to two community hospitals between January 2001 and December 2011, were compared between patients who were VTE positive and those who were VTE negative. The primary goal of this study was to determine whether VTE positive cancer patients had higher tumor marker levels compared to VTE negative cancer patients. In our study, 66.7% (48/72) of patients who were positive for VTE had elevated tumor markers while 65.3% (66/101) of patients who were negative for VTE had low (normal) tumor markers, indicating an association of high tumor marker levels with the diagnosis of VTE. This was statistically significant with an odds ratio of 3.77 and p-value of <0.0001 (95% CI of 1.99–7.14). When the VTE group was further divided into DVT and PE groups, 70.2% (40/57) of patients in the DVT positive group had high tumor markers with a p value of <0.0001 and an odds ratio of 3.99 (95% CI of 2.02 to 7.89) while 57.9% (11/19) of patients in pulmonary embolism positive group had high tumor markers; this was, however, not statistically significant (p-value of 0.35 and a CI of 0.59 to 4.10). In this retrospective study of 173 individuals with a diagnosis of either colorectal, pancreatic, or ovarian Cancer, higher tumor marker levels (CEA, CA 19–9, and CA 125 respectively) were associated with an increased risk of VTE, either DVT or PE. However, when further divided into either DVT or PE groups, the association remained statistically significant only for DVT but not for PE.