Adverse Prognostic Factor For Survival Research Articles

Are all palpable lymph nodes positive in penile cancer? retrospective study

Background: Though rare in western countries the incidence of penile cancer in India is much higher and can represent 10-20% of malignant diseases in men ranging from 0.7-3 per 100,000. Important risk factors include phimosis, chronic inflammatory conditions, treatment with sporalene and ultraviolet A photo chemotherapy, smoking, sexual history and HPV DNA. Smegma as a carcinogen has been clearly excluded. In our country where incidence of inguinal nodes are high due to bare foot walking and infection, there must be balance between loosing patients from lack of follow-up and presenting later with inoperable inguinal nodes and the morbidity of a groin dissection. Methods: This is 5 year retrospective study of carcinoma penis from a single institute (2007-2012). 50 cases have been included in this study. 20 of the 50 cases had clinically significant nodes of which only 14 cases were fine needle aspiration cytology positive nodes and they had been addressed with an inguinal block dissection in the same sitting with the primary. In first 6 months 8 cases had positive nodes on follow-up and between 6 months to 2 years 10 patients developed node recurrence and underwent block dissection. Results: Median follow-up was 21.8 months. Among these 6 patients lost to follow up. All the follow up patients who underwent surgery on later date had one or more of these factors: High primary tumour grade, > pT2 status, lymphovascular invasion, pelvic lymph node involvement, extra nodal extension. Pelvic lymph node dissection was done in 4 patients. Adjuvant radiotherapy was given in 12 patients (37%) and chemotherapy in 4 patients (12%). Overall 5-year cancer specific survival was 61%. Men with extra nodal extension and pelvic lymph node involvement had significantly decreased 5-year cancer specific survival compared with men without it (42% vs. 80%). Complications of inguinal block dissections were flap necrosis, wound infection, seroma formation, lymphedema and deep vein thrombosis. Recognised adverse prognostic factors for survival in carcinoma penis were pathological T stage (>T2), differentiation grade (high grade > low grade), positive margin status, extra nodal extension, 4 or more unilateral metastatic inguinal nodes, bilateral versus unilateral metastatic involvement and pelvic lymph node involvement. Conclusions: In Indian population, cases with carcinoma penis are generally of higher T status on presentation. Lymph nodes were palpable in majority of cases but most were not pathologically positive. Prophylactic block dissections are not practical as it carries its own morbidity and complications. High incidence of pathologically positive nodes were seen in patients with high grade, T status and lymphovascular invasion.

Survival outcomes in Egyptian patients with triple-negative breast cancer: Single institute experience.

158 Background: Triple-negative breast cancer (TNBC) is a unique subtype and consider as an aggressive disease without established targeted treatment options. This study conducted to determine the incidence, characteristics, and survival outcomes of TNBC patients in an Egyptian cancer institute. Methods: Medical records of 520 patients treated between 2010-2011 in Clinical Oncology Department-Ain Shams University-Egypt were analyzed. Cox proportional hazards models were used to evaluate the association between TNBC and DFS and OS after adjusting for other covariates. Results: Among the 520 patients, 139 were TNBC .The median age was 50 years (SD±11.767, Range 20-80 ) versus 52 years (SD±12.134, Range 20-80), median tumor diameter was 5 cm (SD± 1.408, Range 1-7) versus was 5 cm (SD± 1.401, Range 1-7) , and median number of positive axillary LN was 3 (SD± 4.779, Range 0-37) versus 3 (SD± 4.832, Range 0-25) in non TNBC and TNBC respectively . Median disease-free survival was 24 months (SD± 14.128, Range 1-69 ) versus 15 months (SD± 8.811, Range 1-43 ) and median overall survival was 41 months (SD± 16.249, Range 3-60) versus 31 months (SD± 12.184, Range 7-60 ) in non TNBC and TNBC respectively. About 85.6 % of the TNBC tumors were IDC, 4.4 % were ILC and 5% were mixed. About 1.4 % of the TNBC tumors were grade I, 70.5 % were grade II and 28.1% were grade III. Median disease-free survival was 24 months (95%CI 21.679- 26.321) versus 15 months (95%CI 12.587-17.413) (p< 0.001) and median overall survival was 44 months (95%CI 41.396-46.604) versus 31 months (95%CI 29.460-32.540) (p< 0.001) in non TNBC and TNBC respectively. In TNBC cohort , DFS was 12 months (95%CI 11.464-12.536) in patients with grade III tumors versus 25 months (95%CI 22.359-27.641 )in patients with other grades (p< 0.001), this was also reflected in OS as 29 months (95%CI 25.129-32.871 ) versus 44 months (95%CI 41.238-46.762 ) (p< 0.001). Conclusions: Multivariate analyses supported a conclusion that TNBC subtype was an independent adverse prognostic factor for survival along with other known risk factors such as tumor grade.

CXC chemokine receptor 2 is associated with postoperative recurrence and survival of patients with non-metastatic clear-cell renal cell carcinoma

BackgroundAberrant CXC chemokine receptor 2 (CXCR2) expression has been shown to promote angiogenesis and proliferation in renal cell carcinoma (RCC). Our current study aims to evaluate the prognostic significance of CXCR2 in patients with non-metastatic clear-cell renal cell carcinoma (ccRCC). MethodsWe retrospectively enrolled 375 patients with non-metastatic ccRCC undergoing nephrectomy at Zhongshan Hospital, Fudan University between 2003 and 2008. The cohort was split into a training set (n=184) and a validation set (n=191). CXCR2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated. ResultsCXCR2 expression was significantly associated with tumour size (P=0.036 and P=0.016, respectively) and Fuhrman grade (P=0.009 and P=0.001, respectively) in the training and validation sets. Moreover, high CXCR2 expression indicated poor overall survival (OS) (P<0.001 and P=0.001, respectively) and recurrence-free survival (P<0.001 and P<0.001, respectively) in the training and validation sets. The incorporation of CXCR2 into the T stage and Fuhrman grade would help to refine individual risk stratification. Furthermore, CXCR2 expression was identified as an independent adverse prognostic factor for survival (P<0.001) and recurrence (P<0.001). A predictive nomogram was generated with identified independent prognosticators to assess patient recurrence-free survival at 5 and 10years. ConclusionsCXCR2 is a potential independent adverse prognostic biomarker for recurrence and survival of patients with non-metastatic ccRCC after nephrectomy.

Prognostic significance of β1,6-N-acetylglucosaminyltransferase V expression in patients with hepatocellular carcinoma.

Alterations to the N-glycans in glycoproteins have been suggested to play important roles in the proliferation, differentiation, invasion and metastasis of hepatocellular carcinoma (HCC). This study aims to evaluate the potential prognostic value of β1,6-N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma patients after surgical resection. We retrospectively enrolled 300 patients (156 in the training cohort and 144 in the validation cohort) with hepatocellular carcinoma undergoing hepatectomy at a single institution. Mgat5 intensities were assessed by immunohistochemistry in the specimens of patients. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy. Intratumoral Mgat5 expression was significantly higher than non-tumoral tissues (P < 0.001). In both cohorts, elevated Mgat5 expression in tumor tissues positively correlated with vascular invasion and advanced tumor-node-metastasis stage. High Mgat5 expression indicated poor survival (P < 0.001 in the training cohort and P < 0.001 in the validation cohort) and recurrence (P < 0.001 in both cohorts, respectively) in patients with hepatocellular carcinoma, particularly with early-stage disease. Mgat5 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of tumor-node-metastasis and Barcelona Clinic Liver Cancer prognostic models was improved when Mgat5 expression was added. Mgat5 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with hepatocellular carcinoma after hepatectomy.

A high baseline HBV load and antiviral therapy affect the survival of patients with advanced HBV-related HCC treated with sorafenib.

Although a high viral load is an independent risk factor for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after surgery, the prognostic impact of viral load on advanced HCC is unclear. This study investigated the impact of baseline HBV load and antiviral therapy on survival of patients with advanced HCC treated with sorafenib. Of 130 patients with advanced HBV-related HCC received first-line sorafenib therapy were evaluated in a multicenter, retrospective study. No patients experienced severe hepatic impairment because of HBV reactivation during sorafenib therapy. The median progression-free survival (PFS) and overall survival (OS) of all patients were 5.7 and 9.6 months respectively. Patients with a baseline HBV DNA ≤10(4) copies/ml had significantly better OS than those with >10(4) copies/ml (10.4 vs 6.6 months; P = 0.002), but PFS showed an increasing trend (5.8 vs 4.8 months; P = 0.068). Patients who received antiviral therapy had a better trend in OS than those who did not (12.0 vs 8.3 months; P = 0.058), but there was no difference in PFS (6.4 vs 4.1 months; P = 0.280). In a multivariate analysis, the baseline HBV DNA level >10(4) copies/ml (P = 0.001; hazard ration [HR] = 2.294; 95% CI 1.429-3.676) and antiviral therapy (P = 0.038; HR 0.617; 95% CI 0.390-0.975) were independent predictors of OS. In patients with advanced HBV-related HCC treated with sorafenib, a high baseline HBV load was an adverse prognostic factor for survival. However, survival was significantly improved with the use of antiviral therapy.

P21-activated kinase 1 predicts recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma.

To estimate the impact of p21-activated kinase 1 expression on recurrence and survival of patients with non-metastatic clear cell renal cell carcinoma after surgical resection. We retrospectively enrolled 254 patients (187 in the training cohort and 67 in the validation cohort) with non-metastatic clear cell renal cell carcinoma undergoing nephrectomy at a single institution. Clinicopathological features, overall survival and recurrence-free survival were recorded. p21-activated kinase 1 intensities were assessed by immunohistochemistry of patients' specimens. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy. In both cohorts, elevated p21-activated kinase 1 expression in tumor tissues positively correlated with advanced T stage and Fuhrman grade. High p21-activated kinase 1 expression indicated poor survival and early recurrence of patients with non-metastatic clear cell renal cell carcinoma, especially with early T1-2 stage disease. After backward elimination, p21-activated kinase 1 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of the traditional University of California Integrated Staging System and Mayo Clinic stage, size, grade and necrosis prognostic models was improved when p21-activated kinase 1 expression was added. Elevated expression of p21-activated kinase 1 seems to be an independent adverse prognostic biomarker for recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma after nephrectomy.

β1,6-N-acetylglucosaminyltransferase V predicts recurrence and survival of patients with clear-cell renal cell carcinoma after surgical resection.

β1,6-N-acetylglucosaminyltransferase V (MGAT5), which is required for the biosynthesis of β1,6GlcNAc-branched N-linked glycans attached to cell surface and secreted glycoproteins, accounts for oncogenic growth signal transduction during the development and progression of various malignancies. Our present study aimed to evaluate the impact of MGAT5 expression on recurrence and survival of patients with clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 265 patients (196 in the training cohort and 69 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, overall survival (OS) and recurrence-free survival (RFS) were recorded. MGAT5 intensities were assessed by immunohistochemistry in specimens of patients. Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on OS and RFS. Concordance index (C-index) was calculated to assess predictive accuracy. In both cohorts, MGAT5 expression positively correlated with metastatic and advanced TNM stage. High MGAT5 expression indicated poor survival (P<0.001 in training set and P<0.001 in validation set) and early recurrence (P<0.001 in training set and P=0.004 in validation set) of patients with ccRCC. After multivariate Cox regression analysis, MGAT5 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of TNM, UISS and SSIGN prognostic models was improved when MGAT5 expression was added. MGAT5 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.

Notch1 Predicts Recurrence and Survival of Patients With Clear-cell Renal Cell Carcinoma After Surgical Resection

To evaluate the prognostic significance of Notch1 activation in patients with clear-cell renal cell carcinoma (ccRCC). We retrospectively enrolled 203 patients with ccRCC undergoing nephrectomy at Zhongshan Hospital of Fudan University between 2003 and 2004. Notch1 activation was assessed by immunohistochemical staining of the intracellular domain of Notch1 (ICN1) in specimens of patients. The Kaplan-Meier method, Cox regression models, and Harrell concordance index (C-index) calculation were used to evaluate the prognostic value of ICN1 expression and its association with clinicopathologic features. Tumor tissues from patients with advanced TNM stage and Fuhrman grade exhibited elevated ICN1 expression, which correlated positively with tumor size, Fuhrman grade, and tumor necrosis. Moreover, high ICN1 expression indicated poor overall survival and recurrence-free survival of patients with ccRCC. After backward elimination, ICN1 expression, as well as Fuhrman grade, Eastern Cooperative Oncology Group performance status, and TNM stage, was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of well-established TNM, University of California Integrated Staging System, and Mayo Clinic stage, size, grade, and necrosis prognostic models was improved when ICN1 expression was added. Furthermore, a predictive nomogram was generated with identified independent prognosticators to assess patient survival at 5years after surgery. Notch1 activation is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.

Lack of prognostic value of human epidermal growth factor-like receptor 2 status in inflammatory breast cancer (IBC): a meta-analysis.

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/ neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.

Elevated Expression of N-Acetylgalactosaminyltransferase 10 Predicts Poor Survival and Early Recurrence of Patients with Clear-Cell Renal Cell Carcinoma.

The aim of this study was to evaluate the potential prognostic significance of N-acetylgalactosaminyltransferase 10 (GALNT10) in patients with clear-cell renal cell carcinoma (ccRCC) after surgical resection. We retrospectively enrolled 271 patients (202 in the training cohort and 69 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, overall survival (OS), and recurrence-free survival (RFS) were recorded. GALNT10 intensities were assessed by immunohistochemistry in the specimens of patients. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on OS and RFS. Concordance index (C-index) was calculated to assess predictive accuracy. In both cohorts, elevated GALNT10 expression in tumor tissues positively correlated with advanced TNM stage. High GALNT10 expression indicated poor survival and early recurrence of patients with ccRCC, particularly with early-stage disease. After backward elimination, GALNT10 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of TNM, University of California Los Angeles Integrated Staging System, and stage, size, grade, and necrosis prognostic models was improved when GALNT10 expression was added. GALNT10 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.

Tumor miR-125b predicts recurrence and survival of patients with clear-cell renal cell carcinoma after surgical resection.

The present study aims to evaluate the impact of tumor microRNA-125b (miR-125b) on recurrence and survival of patients with clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 276 patients (200 in the training cohort and 76 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, cancer-specific survival (CSS) and recurrence-free survival (RFS) were recorded. Tumor miR-125b levels were assessed by in situ hybridization (ISH) in specimens of patients. The Kaplan–Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on CSS and RFS. A concordance index (C-index) was calculated to assess predictive accuracy. In both cohorts, tumor miR-125b positively correlated with Fuhrman grade. High tumor miR-125b indicated poor survival and early recurrence for patients with ccRCC, especially with advanced stage disease. After multivariable adjustment, tumor miR-125b was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of traditional TNM and UCLA Integrated Staging System prognostic models was improved when tumor miR-125b was added. The results showed that tumor miR-125b is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone.

IntroductionPhosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations and PTEN low in patients receiving paclitaxel alone or in combination with lapatinib.MethodsImmunohistochemistry and mutation analyses were used to evaluate PTEN and PIK3CA, respectively. Kaplan-Meier analysis with log-rank tests, logistic regression and Cox models were used in analyses of these biomarkers with efficacy endpoints.ResultsIn the overall population, PIK3CA mutations were associated with poorer overall survival (OS) (hazard ratio (HR) = 1.87; 95% confidence interval (CI): 1.22, 2.88; P = 0.001). PTEN expression was not associated with OS (P = 0.474). In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179). In the PTEN low group, OS was improved with addition of lapatinib (P = 0.039). In both PTEN subgroups, addition of lapatinib was associated with improvements in PFS (P <0.050). PIK3CA and PTEN were not predictive of treatment based on interaction tests (P >0.05).ConclusionsPTEN was neither a significant prognostic nor predictive factor. PIK3CA mutations were an adverse prognostic factor for survival but not predictive for lapatinib benefit.Trial registrationClinicalTrials.gov NCT00281658 (registered 23 January 2006)Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0405-y) contains supplementary material, which is available to authorized users.

Outcome of children with relapsed acute myeloid leukemia following initial therapy under the AML99 protocol.

The outcomes of children with relapsed acute myeloid leukemia (AML) are known to be poor, but remain obscure. We retrospectively analyzed 71 patients who had relapsed following first-line treatment under the AML99 protocol. We investigated the time and site of recurrence, response to re-induction therapy, and performance of hematopoietic stem cell transplantation (HSCT) in relapsed cases, and performed a multivariate analysis to identify prognostic factors. The 5-year overall-survival (OS) rate after relapse was 37 %. Of 71 patients, three died without any anti-leukemic therapy and two underwent allogeneic HSCT. The remaining 66 patients received re-induction chemotherapy, and 33 (50 %) achieved second CR (CR2). Twenty-two of 25 (88 %) late relapse patients and 11 of 41 (27 %) early relapse patients achieved CR2 (P < 0.001). Twenty-nine CR2 cases and 35 non-CR2 cases underwent allogeneic HSCT. The 5-year OS rate was significantly higher in patients who underwent HSCT in CR2 than those in non-CR2 (66 vs. 17 %, P < 0.000001). Multivariate analysis indicated that early relapse (P < 0.05) and the positivity of the FMS-like tyrosine kinase 3--internal tandem duplication (P < 0.05) were adverse prognostic factors for survival. In conclusion, the etiology of relapsed pediatric AML needs to be elucidated and effective chemotherapy should be administered to obtain CR2.

Deregulated Expression ofEVI1Defines a Poor Prognostic Subset ofMLL-Rearranged Acute Myeloid Leukemias: A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group

To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements. We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis. We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1(+)) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1(+) was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1(+) AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1(-) t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1(+) again was the sole independent adverse prognostic factor for survival. Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1(+) MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.

Uterine Artery Pulsatility Index as an Emerging Promising Marker in the Management of Gestational Trophoblastic Neoplasia

ABSTRACT Objective Increasing new blood vessel formation (neoangiogenesis) within tumors is one of the adverse prognostic factors for survival in several cancers. Neoangiogenesis in vivo can be assessed by Doppler ultrasonography by measuring uterine artery pulsatility index (UAPI) in patients with gestational trophoblastic neoplasia (GTN). In this study we assessed whether UAPI can be an independent prognostic factor predictive of response to chemotherapy. Methods This was a prospective observational study conducted in Medical College, Kolkata from May 2011 to December 2012. Twenty-two patients of GTN had their FIGO prognostic scoring done, 19 patients were of low risk (scored ≤T6) and three patients were of high risk (score &gt; 6). The 3 high risk GTN patients were excluded from the study. The study population therefore consisted of 19 low risk (scored ≤6) patients of GTN who were treated with fortnightly cycles of 50 mg of methotrexate IM on days 1, 3, 5 and 7 and with 15 mg of folinic acid rescue IM on days 2, 4, 6 and 8. Treatment was continued in all patients till hCG values were negative and 2 further cycles of chemotherapy were given. The patients were followed up with UAPI and serum β-hCG levels every 2 weeks following chemotherapy to assess whether fall in β-hCG correlated with rise in UAPI values following chemotherapy. Data collected were analyzed using standard statistical protocol. Results The β-hCG concentration of these patients at the time of diagnosis ranged from 1400 to 210,000 mIU/ml and UAPI varied from 0.47 to 2.1. The mean β hCG of these 19 patients before chemotherapy (week 0) was 63705.47 mIU/ml and subsequently following chemotherapy at the end of 16 weeks was 1.64 mIU/ml. The mean UAPI before chemotherapy (week 0) was 1.33 and following chemotherapy at the end of 16 weeks was 1.952. All patients achieved complete remission with chemotherapy. The fall in beta-hCG levels corelated with the rise in UAPI values. Conclusion This study provides proof of principle that the UAPI can serve as a noninvasive in vivo measure of functional tumor vascularity, which independently can predict the response to chemotherapy. How to cite this article Kyal A, Mukhopadhyay P, Bag TS, Saha DP, Neogi M, Soreng P. Uterine Artery Pulsatility Index as an Emerging Promising Marker in the Management of Gestational Trophoblastic Neoplasia. J South Asian Feder Obst Gynae 2013;5(3):139-141.

Clinical and prognostic implications of low or high level of von Willebrand factor in patients with Waldenström macroglobulinemia

AbstractAcquired von Willebrand syndrome is described in patients with Waldenström macroglobulinemia (WM). Assessment of ristocetin cofactor activity (VWF:RCo) and von Willebrand factor (VWF) antigen (VWF:Ag) in 72 consecutive patients with WM showed a negative relation between VWF levels < 130 U/dL and both monoclonal immunoglobulin M concentration (mIgMC) and viscosity. Ten patients with VWF:RCo < 50 U/dL (< 40 for patients with blood group O) fulfilled the acquired von Willebrand syndrome criteria. They had higher mIgMC and viscosity. Reduction in mIgMC was associated with increase in VWF levels. The low VWF:RCo/VWF:Ag ratio suggested that high viscosity might be associated with increased shear force and cleavage of multimers. Surprisingly, 43 patients (59%) presented with high VWF:Ag (> 110 U/dL). They had higher bone marrow microvessel density and vascular endothelial growth factor expression on bone marrow mast cells. Five-year survival rates of patients with VWF:Ag < 110, between 110 and 250, and more than 250 U/dL were 96%, 71%, and 44%, respectively (P < .0001). High VWF:Ag was also a significant adverse prognostic factor for survival after first-line therapy (P < .0001), independently of the international scoring system. These results support systematic assessment of VWF in patients with WM. The adverse prognostic value of high VWF levels raises issues on interactions between lymphoplasmacytic cells, mast cells, and endothelial cells in WM.

The prognostic impact of clinical and molecular features in hairy cell leukaemia variant and splenic marginal zone lymphoma

Hairy cell leukaemia variant (HCL-variant) and splenic marginal zone lymphoma (SMZL) are disorders with overlapping features. We investigated the prognostic impact in these disorders of clinical and molecular features including IGH VDJ rearrangements, IGHV gene usage and TP 53 mutations. Clinical and laboratory data were collected before therapy from 35 HCL-variant and 68 SMZL cases. End-points were the need for treatment and overall survival. 97% of HCL-variant and 77% of SMZL cases required treatment (P = 0·009). Survival at 5 years was significantly worse in HCL-variant [57% (95% confidence interval 38-73%)] compared with SMZL [84% (71-91%); Hazard Ratio 2·25 (1·20-4·25), P = 0·01]. In HCL-variant, adverse prognostic factors for survival were older age (P = 0·04), anaemia (P = 0·01) and TP 53 mutations (P = 0·02). In SMZL, splenomegaly, anaemia and IGHV genes with >98% homology to the germline predicted the need for treatment; older age, anaemia and IGHV unmutated genes (100% homology) predicted shorter survival. IGHV gene usage had no impact on clinical outcome in either disease. The combination of unfavourable factors allowed patients to be stratified into risk groups with significant differences in survival. Although HCL-variant and SMZL share some features, they have different outcomes, influenced by clinical and biological factors.

AOS23 O6-methylguanine-DNA-methyltransferase expression in Thai patients with malignant gliomas: Outcome and response to treatment in Ramathibodi Hospital

Background Malignant glioma is a rare but fatal tumour. High expression of O6-methylguanine-DNA-methyltransferase (MGMT) has been linked to poor outcome. We investigated the frequency of MGMT expression and its correlation with outcome and response to treatment in Thai patients. Methods In a retrospective cohort study of adult patients with histologically confirmed WHO grade III and IV malignant glioma diagnosed at Ramathibodi Hospital between January 1997 and December 2009, tumour tissue was assayed for MGMT immunohistochemistry status using MT 3.1 antibody with normal brain as the internal control. Data for clinical characteristics, treatment details, and outcome were collected. The main objective was the frequency of MGMT overexpression. Secondary outcomes were the correlation of MGMT expression with survival and treatment response. Findings One hundred thirty-five patients were eligible for analysis. The median age was 47 years. The most common histology was glioblastoma multiforme (WHO grade IV, 54.8%). Only 97 specimens were available for MGMT analysis and overexpression was detected in 31%. Median overall survival (OS) was 11.9 months and 1-year, 2-year, and 5-year OS was 50% (95% confidence interval (CI), 0.41–0.58), 34% (95% CI, 0.26–0.42), and 21% (95% CI, 0.14–0.29), respectively. Four significant adverse prognostic factors for survival that were identified in a multivariate analysis were diabetes mellitus, neurological deficit at diagnosis, histology of glioblastoma multiforme, and receipt of only single treatment modality. MGMT expression did not have prognostic value in the univariate and multivariate analyses. There was no difference in overall survival or response to treatment with temozolamide/BCNU in the subgroup with low MGMT compared with high MGMT. Interpretation The prevalence of MGMT expression in Thai patients with malignant glioma was not different from that reported elsewhere. MGMT expression did not affect outcome in this study cohort. Therefore, considering MGMT as a relevant factor in selection for treatment with temozolamide might be premature. Funding Faculty research grant from Ramathibodi Hospital. The authors declared no conflicts of interest.

Liver Transplantation for HCC: A Review.

Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease or cirrhosis. Liver transplantation for hepatocellular carcinoma has the potential to eliminate both the tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver as well as massive HCC in noncirrhotic liver. Limitations in organ availability, necessitate stringent selection of patients who would likely to derive most benefit. Selection criteria have considered tumor size, number, volume as well as biological features. The Milan criteria set the benchmark for tumors that would benefit from liver transplantation but were found to be excessively restrictive. Modest expansion in criteria has also been shown to be associated with equivalent survival. Microvascular invasion is the single most important adverse prognostic factor for survival. Living donor liver transplantation has expanded donor options and has the advantage of lower waiting period and not impacting the non-HCC waiting list. Acceptable outcomes have been obtained with living donor liver transplantation for larger and more numerous tumors in the absence of microvascular invasion. Downstaging of tumors to prevent progression while waiting for an organ or for reduction in size to allow enrolment for transplantation has met with variable success.