Impact of targeted treatment in non-Hodgkin’s lymphoma with primary lymph node involvement

Background: Non-Hodgkin’s lymphomas (NHL) are malignant tumors that develop from lymphoid tissue. Primary lymph node (LN) involvement is the most common localization (52-70%). The integration of Rituximab (R) in the NHL treatment represented a turning point. The aim of this study was to evaluate the therapeutic impact of the use of R in combination with conventional polychemotherapeutic (PChT) in the treatment of nodal onset NHL. Material and methods: A descriptive cohort study was performed on 80 patients diagnosed with NHL. Results: In the study participated: men – 39(48.8%), women – 41(51.2%). The mean age of the patients was 56.09 ± 13.6 years. The onset of NHL occurred in peripheral l/n in 85.0% of cases, in mediastinal LN – 7.5%, and abdominals in 7.5%. Stages I-II were identified in 21(26.2%) patients, stages III-IV in 59(73.8%) cases. Aggressive NHLs were diagnosed in 54(67.5%) patients, indolent NHLs in 26(32.5%) cases. In 61(76.3%) patients, first-line R+PChT treatment was applied – group 1(G1), and in 19(23.8%) cases conventional PChT was applied – group 2(G2). The overall response rate (ORR) in G1 was 86.8%, in G2 – 63.1%. Complete remissions (CR) were obtained in G1 in 63.9% of patients, in G2 – 47.3% of cases. Progression-free survival (PFS) in G1 had a median of 20 months, and in G2 the median was 12 months (p <0.05). Conclusions: The use of Rituximab increased the ORR rate (86.8% vs 63.1%), the frequency of CR (63.9% vs 47.3%) and PFS (20 months vs 12 months (p <0.05).

Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma

Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

RECENT ADVANCEMENT ON ISOLATION, ACTIVATION AND CRYOPRESERVATION OF LYMPH NODE CELLS IN MICE.

ABSTRACT Lymph nodes are found within the body has B, T and other immune cells and help to filter and trap foreign particles. Like any other primary culture lymph node culture would retain many of differentiated characteristics of cells in vivo thus they have potential for acting as alternative method to mammalian model. For setting up primary lymph node culture in mice different types of lymph nodes were collected from mice followed with isolation, activation and cryopreservation of cells from lymph node. The present review emphasize on various procedures used for isolation, activation and cryopreservation of lymph node cells. Isolation of cells was performed by collagenase digestion, teasing apart of lymph node using dissecting needle or lymph nodes were disrupted between two frosted slides. Concanavalin A have been widely used to stimulate mice lymph node cells. Low dose of Con A have stimulatory effect on T cells but high dose have inhibitory action and caused suppression of proliferation of T cell. Balb/c mice and C57Bl/6 mice were used for different dose of Con A. The addition of cryoprotective agents, e.g.dimethylsulphoxide and careful control of cooling rates affords protection from cell damage during freezing.

A New Surveillance Algorithm After Resection of Colorectal Liver Metastases Based on Changes in Recurrence Risk and RAS Mutation Status

Background: The optimal surveillance strategy after resection of colorectal liver metastases (CLM) is unknown. We evaluated changes in recurrence risk after CLM resection and developed a surveillance algorithm. Methods: Patients undergoing CLM resection during 1998 to 2015 were identified from a prospectively compiled database and analyzed if they had the potential for follow-up longer than the longest observed time to recurrence in this cohort. Changes in recurrence risk and risk factors for recurrence were evaluated. All statistical tests were 2-sided. Results: Among 2,105 patients who were initially identified and underwent CLM resection, the latest recurrence was observed at 87 months; 1,221 consecutive patients from 1998 through 2011 with the potential for at least 87 months of follow-up were included. The risk of recurrence was highest at 0 to 2 years after CLM resection, lower at 2 to 4 years after CLM resection, and steadily lower after 4 years after CLM resection. Factors associated with increased recurrence risk at the time of surgery were primary lymph node metastasis (hazard ratio [HR], 1.54; 95% CI, 1.21–1.97; P<.001), multiple CLM (HR, 1.31; 95% CI, 1.06–1.63; P=.015), largest liver metastasis diameter >5 cm (HR, 1.64; 95% CI, 1.23–2.19; P<.001), and RAS mutation (HR, 1.29; 95% CI, 1.04–1.59; P=.020). In patients without recurrence at 2 years, the only factor still associated with increased recurrence risk was RAS mutation. In those patients, the recurrence rate at 4 years was 59.3% in patients with RAS mutation versus 27.8% in patients with RAS wild-type (P=.019). Conclusions: For patients who have undergone CLM resection, we propose surveillance every 3 to 4 months during years 0 to 2, every 3 to 4 months (if mutant RAS) versus every 4 to 6 months (if RAS wild-type) during years 2 to 4, and every 6 to 12 months if recurrence-free at 4 years.