Effects of Operating Conditions on Selectivity of a Plasma Fractionator in Double Filtration Plasmapheresis

Abstract: In a typical double filtration plasmapheresis treatment, plasma fractionation between albumin and some immunoglobulins associated with toxins is limited because none of the currently available plasma fractionators has a strict cutoff property for these proteins. Selectivity of immunoglobulins over albumin depends not only on the cutoff properties of the membrane but on the operating conditions such as the flow rate of the supplied plasma (Q_p ) and retained plasma to be discarded (Q_d ) in the plasma fractionator. We carried out an in vitro study using human plasma harvested by single plasma exchange treatments to assess the selectivity of a plasma fractionator, Evaflux 2A‐F (Kawasumi Laboratories, Inc., Tokyo, Japan), under various operating conditions. The results of rate‐constant filtration experiments showed that the concentrations in the feed tank and the sieving coefficient (SC) values of every protein were decreased slightly within 2 h after the start of the experiment because of membrane trapping, adsorption, and/or plugging. The time‐averaged SC value of albumin increased with flow rate ratio (Q_p /Q_d ) due to increasing filtration fraction (FF), but relative removal efficiency (m_D/m_P*) for albumin decreased with Q_p /Q_d due to decreasing Q_d . For immunoglobulins, on the other hand, the SC values were almost unchanged, and the m_D/m_P* values increased with Q_p /Q_d due to an increase in FF. Both increasing Q_p and decreasing Q_d are effective means of improving selectivity between these proteins in the plasma fractionator. Membrane fouling is, however, obvious beyond a Q_p /Q_d value that is thought to be a critical point. Operation should be conducted below the critical Q_p /Q_d value, which depends on the patient's plasma components and the cutoff property of the membrane.     

Immunohistochemical differences in gastric mucosal damage between nodular and non-nodular gastritis caused by Helicobacter pylori infection

In this study, the level of cell damage were analyzed immuno­histochemically to clarify the association between nodular gastritis and undifferentiated gastric cancer. Thirty patients of nodular gastritis were enrolled as the nodular gastritis group. Thirty patients of non-nodular gastritis were enrolled as the control group. They were evaluated according to the updated Sydney system and used for immunohistochemical staining (p53, Ki-67, E-cadherin, and 8-OHdG). The scores based on the updated Sydney system were significantly higher in the nodular group than in the non-nodular group for histologically assessed inflammation and activity in the gastric corpus (1.91 ± 0.77 vs 1.58 ± 0.60, p = 0.049, 0.83 ± 0.81 vs 0.44 ± 0.64, p = 0.032). On immunostaining, the detection of E-cadherin was lower in the nodular group for both the antrum (1.0 ± 0.62 vs 1.47 ± 0.85, p = 0.047) and the corpus (1.16 ± 0.81 vs 1.48 ± 0.71, p = 0.043) and the p53 labeling index of the gastric corpus was higher in the nodular group than in the non-nodular group (3.06 ± 1.94 vs 2.03 ± 1.99, p = 0.015). Nodular gastritis showed significant severe inflammation and immunohistochemical cell damage compared with non-nodular gastritis. These findings may play an important role in the oncogenesis of undifferentiated gastric cancer in nodular gastritis.     

Placental site trophoblastic tumor (PSTT) with multiple metastases and extremely poor prognosis

Placental site trophoblastic tumor (PSTT) is a rare type of gestational trophoblastic disease. There is a wide clinical spectrum of presentation and behavior ranging from a benign condition to an aggressive disease with a fatal outcome. PSTT limited to the uterus is in a good prognosis group, but PSTT with metastasis is a lethal disease. We document a case of PSTT with multiple metastases and extremely poor prognosis. A 36-year-old woman had abnormal irregular vaginal bleeding 14 months after her third pregnancy and delivery. The mitotic count of the tumor cells was quite high (23/10 high-power fields). It would have been difficult to remove the tumor by surgery because of the tumor size and its invasion, so we suggested chemotherapy. We treated her with EMA/CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) as a first-line regimen. During the sixth cycle of EMA/CO, the disease became drug-resistant and she died 8 months after the first symptom. This was a rare case among documented patients with PSTT with metastasis, with the patient having short-term survival (<1 year). We conclude that a high mitotic count and atypical undifferentiated pathological features are significant poor prognostic factors for survival in PSTT.     

Analysis of stage IVB endometrial carcinoma patients with distant metastasis: a review of prognoses in 55 patients

Background  

Adequate treatment for extremely advanced endometrial cancer is unknown. The purpose of this study was to clarify the prognosis of patients with stage IVB endometrial carcinoma and the validity of treatment. Furthermore, we evaluated whether there was a connection between the prognosis and the site of metastasis.     

Distinctive cell properties of B cells carrying the BCL2 translocation and their potential roles in the development of lymphoma of germinal center type

The BCL2/IGH translocation is a hallmark of follicular lymphoma and germinal center B-cell type diffuse large B-cell lymphoma. Although a strong determinant of these histological subtypes, this translocation is insufficient by itself for lymphomagenesis, so that other genetic alterations are required. To clarify how the BCL2 translocation contributes to the development of specific lymphoma subtypes, we used chimeric mouse models and a bone marrow transplantation system to examine the biological features of BCL2 -overexpressing B cells. These cells showed a cell-autonomous differentiation preference for follicular B cells. Their cell cycle progression was enhanced in wild-type but not in Eμ-BCL2 transgenic mice, indicating that the low proliferative activity of B cells in Eμ-BCL2 transgenic mice is partly due to their specific microenvironment, which is caused by the abnormal B cells themselves. Moreover, in vitro experiments demonstrated that Eμ-BCL2 ⁺ B cells have reduced responsiveness to terminal differentiation stimulation. According to these results, we hypothesize that B cells that have undergone BCL2/IGH translocation might possibly be forced to localize in follicles, and accumulate genetic abnormalities by being subjected to recurrent stimulation. Our findings lead us to propose that B cells carrying the BCL2/IGH translocation comprise a distinctive cell population that leads to the development of germinal center B-cell type lymphoma. ( Cancer Sci 2009; 100: 2361–2367)     

A follow-up report on a new method of segmental resection for small-sized early lung cancer

We previously reported a new method of segmentectomy, pulmonary artery-guided segmentectomy as a surgical alternative for small-sized early lung cancer with favorable results, but the follow-up time was too short for definitive conclusion. To examine the efficacy of the segmentectomy, and to determine the appropriate surgical procedure for early lung cancer, we conducted a retrospective follow-up study, and examined the influences of tumor size and preoperative serum tumor marker levels on the prognosis. We reviewed the records of 91 patients who underwent the segmentectomy for pathological T1N0M0 non-small cell lung cancer from 1993 to 2002. In 85 patients, carcinoembryonic antigen, squamous cell carcinoma-related antigen, and a fragment of cytokeratin were measured preoperatively. The overall 5-year survival rate was 83%. Indication (intentional, n=47; compromised, n=44) and tumor size (20mm or less, n=68; 21 to 30 mm, n=23) had no significant impact on survival. The 5-year survival rate for 49 patients with normal tumor marker levels was 93%, and significantly higher than 36 patients with at least one elevated tumor marker level (68%, p<0.01). Median follow-up time of 72.0 months revealed 11 locoregional recurrences. The incidence of locoregional recurrence was significantly higher in the patients with tumors of 21-30 mm, and elevated tumor marker (p<0.01). The follow-up study demonstrated that the segmentectomy could be an acceptable surgical treatment for early lung cancer patients with tumors of 20mm or smaller and normal tumor marker levels.