[Comparison of the efficacy and safety of 2 low-dose rituximab regimens in the second-line treatment of primary immune thrombocytopenia in children].

Objective: To compare the efficacy and safety of 2 low-dose rituximab regimens in the treatment of children with primary immune thrombocytopenia (ITP). Methods: A total of 90 ITP children admitted to the Hematology Oncology Center of Beijing Children's Hospital from January 2018 to March 2021 were enrolled in this prospective cohort study. In the single-dose group, rituximab was given with a single dose of 375 mg/m2 (maximum dose 600 mg). In the 4-dose group, rituximab was given with a dose of 100 mg weekly (if body weight of the patient ≥ 30 kg, increase dosage to 200 mg weekly) for 4 weeks. Wilcoxon Mann-Whitney test, Chi-square test and Fisher's exact test were used to analyze the difference in efficacy, safety and treatment burden between two groups. Results: Among the 90 children, 41 were male and 49 were female, and the age of medication was 6.8 (4.1,10.0) years. There were 27 cases in the single-dose group and 63 cases in the 4-dose group.There were no significant differences in overall response rate, complete response rate and partial response rate between the single-dose group and 4-dose group (41% (11/27) vs. 33% (21/63), 26% (7/27) vs. 19% (12/63), 15% (4/27) vs. 14%(9/63), χ2=0.45, 0.54, 0.00, all P>0.05). The single-dose group was earlier to get overall response than the 4-dose group (1 (1, 1) vs. 3 (2, 6) weeks, Z=-3.24, P=0.001). There were no significant differences in the sustained response rate, the overall response rate in 1 year, the complete response rate in 1 year, and the partial response rate in 1 year between the single-dose group and the 4-dose group (33% (9/27) vs. 30% (19/63), 30% (8/27) vs. 24% (15/63), 19% (5/27) vs. 14% (9/63), 11% (3/27) vs. 10% (6/63), χ2=0.09, 0.34, 0.04, 0.00, all P>0.05). There were no significant differences in the duration of overall response, recurrence rate within half a year and one year, recurrence time and rate of adverse events between the single-dose group and 4-dose group (all P>0.05). The number of hospitalizations, the duration of hospital stays and the dosage of the single-dose group were significantly lower than those of the 4-dose group (1 (1, 1) vs. 4 (4, 4) times, 5 (4, 7) vs. 8 (5, 8) d, 400 (250, 500) vs. 400 (400, 800) mg, Z=-8.67, -3.03, -4.05, all P<0.05). Conclusions: The single-dose rituximab regimen is comparable to 4-dose rituximab regimen in effectiveness and safety for treatment of children ITP, but more economical and convenient. The single-dose rituximab regimen is more suitable for the second-line treatment of children ITP.

[Autologous versus unrelated donor stem cell transplantation for adults with primary acute myeloid leukemia in first remission].

Objective: To compare differences of autologous and unrelated donor stem cell transplantation (auto-HSCT and URD-HSCT) for adults with primary acute myeloid leukemia (AML) in first complete remission (CR(1)) from a single center and to investigate the appropriate patients for the 2 types of transplant. Methods: In this retrospective investigation, we studied adults with primary AML who received auto-HSCT and URD-HSCT from March 2008 to November 2018. Overall survival (OS) , leukemia-free survival (LFS) , relapse, transplant-related mortality (TRM) , and hematopoietic reconstitution were compared along with the prognostic value of cytogenetics. Results: A total of 147 adult patients were enrolled in this study (n=87 for auto-HSCT and n=60 for URD-HSCT) . Baseline characteristics were comparable between the 2 groups. The accumulative neutrophil engraftment rate at +30 days was not statistically different between the 2 groups[92.6% (95% CI 86.9%-98.3%) vs 98.3% (95% CI 95.0%-100.0%) , P=0.270], whereas the accumulative platelet engraftment rate at +60 days was significantly lower in the auto-HSCT group[83.6% (95% CI 75.8%-91.4%) vs 93.3% (95% CI 87.0%-99.6%) , P<0.001]. In patients undergoing URD-HSCT, the accumulative incidences of acute GVHD (aGVHD) and grade Ⅱ-Ⅳ aGVHD were 56.7% (95% CI 43.0%-68.2%) and 16.7% (95% CI 8.5%-27.2%) , and the incidences of chronic GVHD (cGVHD) and extensive cGVHD were 33.3% (95% CI 21.7%-45.4%) and 15.0% (95% CI 7.3%-25.2%) , respectively. After a median follow-up of 53.8 (0.8-127.8) months, patients in the 2 groups demonstrated comparable OS and LFS at 5 years after transplant[71.7% (95% CI 61.7%-81.7%) vs 67.8% (95% CI 55.8%-79.8%) , P=0.556; 64.6% (95% CI 54.4%-74.8%) vs 68.1% (95% CI 56.3%-79.9%) , P=0.642]. Patients in the auto-HSCT group showed significantly higher incidence of relapse at 5 years after transplant[31.9% (95% CI 22.2%-42.1%) vs 15.1% (95% CI 7.4%-25.6%) , P=0.015] and significantly lower incidence of TRM[3.4% (95% CI 0.9%-8.9%) vs 16.7% (95% CI 8.5%-27.2%) , P=0.006] compared with the URD group. HLA mismatching had no effects on the incidences of hematopoietic reconstitution, GVHD, OS, LFS, relapse, and TRM. Patients of cytogenetically favorable and intermediate risk demonstrated comparable OS and LFS after auto-HSCT and URD-HSCT, while patients of poor risk had significantly higher relapse and lower LFS after auto-HSCT. Conclusions: In this study, adults with primary AML in CR(1) demonstrated relatively higher relapse but lower TRM after auto-HSCT, resulting in comparable survival to that of URD-HSCT. In the absence of matched sibling donors, patients of cytogenetically poor risk should receive URD-HSCT in order to achieve lower relapse and better survival.

[Outcomes of 138 myelodysplastic syndrome patients with HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

[HLA-10/10 matched unrelated donor versus sibling donor hematopoietic stem cell transplantation for adult acute myeloid leukemia].

Objective: To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center. Methods: Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed. Results: A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade Ⅲ-Ⅳ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups. Conclusions: The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.

[Prognostic significance of early phase donor chimerism after allogeneic peripheral blood stem cell transplantation].

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion: The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.

[Outcome of acute myeloid leukemia with FLT3-ITD mutation treated by allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of acute myeloid leukemia (AML) patients with FLT3-ITD mutation. Methods: From September 2008 to December 2016, 40 AML patients with FLT3-ITD mutation were enrolled in the study. The therapeutic process, outcomes and prognostic factors were retrospectively analyzed. Results: The median of WBC at initial diagnosis was 35.0 (range 1.7-185.0) ×10(9)/L. The median course number of chemotherapy was 4 (range 2-7). At the time of transplantation, 34 patients were at the first complete remission (CR(1)) stage, and the other 6 ones were non-remission after chemotherapy. 24 patients received allogeneic transplants from an HLA-matched sibling donor, 7 cases from a HLA-matched unrelated donor, the remaining 9 ones received allograft from a haploidentical donor. The rate of 3-year overall survival (OS) and disease free survival (DFS) in all patients were both 74.3% (95% CI 60.4%-88.2%). The 3-year cumulative incidences of disease relapse and non-relapse mortality were 7.5% (95%CI 1.9%-18.4%) and 18.2% (95% CI 7.9%-32.0%), respectively. More than one course of chemotherapy before achieving CR(1) and the occurrence of acute GVHD after transplantation were associated with poor outcome in terms of OS and DFS. The relapse rates were significantly lower in patients receiving transplantation at CR(1) stage [0 vs 50.0% (95%CI 77.7%-82.9%) , P<0.001] and achieving CR(1) after one course induction therapy [0 vs 16.7% (95%CI 3.9%-37.3%) , P=0.020]. Conclusions: Allo-HSCT was an efficient approach for AML patients with FLT3-ITD mutation. Patients obtained better survival, especially for those achieving CR after one course induction therapy and receiving transplantation at CR(1) stage.

[Application of low-dose ATG for GVHD prophylaxis in patients undergoing PBSCT aged over forty years old].

Objective: To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin (ATG) in patients undergoing peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors (MSD) given both the patients and donors were aged over forty years old. Methods: From March 2013 to April 2017, 98 patients with hematologic malignancies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG (Sanofi, 1.5 mg/kg per day for 3 consecutive days) before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed. Results: ①Neutrophil engraftment was achieved earlier in ATG group than the control one [13(11-17)d vs 14(12-24)d, P=0.001]. The time to platelet engraftment was similar between the two groups [14(11-43)d vs 15(11-42)d, P=0.071]. ②The cumulative incidence of aGVHD was significantly lower in ATG group [25.6% (95%CI 13.7%-39.3%) vs 49.1% (95%CI 35.2%-61.6%), P=0.018]. The incidences of grade Ⅱ-Ⅳ aGVHD [18.6% (95%CI 8.6%-31.5%) vs 23.6% (95%CI 13.4%-35.6%), P=0.509] and cGVHD [49.6% (95% CI 31.6%-65.3%) vs 56.4% (95% CI 41.4%-69.0%), P=0.221] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [21.1%(95%CI 10.3%-34.5%) vs 31.1% (95%CI 18.8%-44.2%), P=0.429]. ④The cumulative incidences of disease relapse [24.0%(95%CI 11.5%-38.9%) vs 24.0% (95% CI 12.1%-38.2%), P=0.608), non-relapse mortality [10.2% (95% CI 3.1%-22.1%) vs 21.6% (95% CI 9.4%-37.0%), P=0.411] and DFS [65.8% (95%CI 50.3%-81.3%) vs 54.4% (95%CI 37.7%-71.1%), P=0.955] were comparable between the two groups. 2-year overall survival (OS) was significantly better in ATG group than the control one [83.8% (95% CI 71.8%-90.0%) vs 58.0% (95% CI 42.2%-73.9%), P=0.019]. Conclusion: The addition of low-dose ATG decreased the incidence of aGVHD and improved OS. The incidences of viral infections and disease relapse remained to be similar between the two groups. These results suggested that elderly patients undergoing MSD-PBSCT may benefit from this low-dose ATG containing GVHD prophylaxis regimen.

[Clinical efficacy and safety of porcine antihuman lymphocyte immunoglobulin in alternative donor allogeneic hematopoietic cell transplantation for severe aplastic anemia].

Objective: To compare eficacy and safety of porcine antihuman lymphocyte immunoglobulin (pALG) and rabbit antithymocyte immunoglobulin (rATG) as a part of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) for severe aplastic anemia (SAA). Methods: The clinical data of 46 SAA patients received AD allo-HSCT from January 2006 to November 2016 were retrospectively analyzed. The cohort of patients were divided into two groups based on rATG or pALG as a part of conditioning regimen to compare implantation rate, transplantation related complications and outcome. Results: In rATG group 30 patients achieved ANC reconstitution, 27 patients achieved PLT reconstitution. In pALG group all 16 patients achieved ANC and PLT reconstitutions. There were no significant differences between the two groups in terms of acute graft-versus-host disease (aGVHD) (P=0.475), Ⅲ-Ⅳ grade aGVHD (P=0.876), chronic GVHD (cGVHD) (P=0.309), extensive cGVHD (P=0.687), graft rejection (GR) (P=0.928), bloodstream infection (P=0.443), invasive fungal disease (P=0.829), cytomegalovirus viremia (P=0.095) respectively. Prospective 5-year overall survival (OS) in rATG and pALG groups were (75.1±8.2)% and (53.6±13.3)% with median follow-up of 14(2-102) and 23(4-63) months, respectively (P=0.190). Conclusion: As a part of conditioning regimen, pALG could achieve similar efficacy as rATG, without increasing the incidences of transplantation complications such as GVHD, GR and infection, in the setting of AD allo-HSCT for SAA patients.

[Survival and the value of adjuvant chemotherapy in esophageal squamous cell carcinoma patients with lymphatic metastasis].

Objective: To investigate the prognosis and the value of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with lymphatic metastasis. Methods: From Jan, 2008 to Dec, 2011, 329 patients with ESCC who underwent two-field radical resection(R0), had lymphatic metastasis and survived over three months were enrolled in this study. There were 246 males and 83 females. The median age was 61 years-old. Site of lesion was located at upper- in 23, middle- in 226 and lower-thoracic segment in 80 patients. There were 114 patients treated with surgery alone and 215 patients with adjuvant chemotherapy. Prognostic factors including adjuvant chemotherapy were assessed in ESCC patients with lymphatic metastasis. Results: In 329 ESCC patients with lymphatic metastasis, the 1-, 3-, 5-years overall survival (OS) rate and progress-free survival (PFS) rate were 74.5%, 31.7%, 24.5%, and 55.1%, 27.8%, 24.2%, respectively. Median OS and PFS were 22 and 15 months, respectively. Multivariate analysis showed that, site of lesion and disease stage were independent factors for OS and PFS (P<0.05). Adjuvant chemotherapy was also an independent prognostic factor for OS (P<0.05). Subgroup analysis showed that adjuvant chemotherapy could improve OS mainly in patients of males, ages≤60, tumor length <6 cm, well- or mediated differentiated squamous cell carcinoma, stage pT3, pN2 and ⅢB (P<0.05). Conclusions: ESCC patients with lymphatic metastasis had poor prognosis. Site of lesion and disease stage were important prognositic factors for survival. Adjuvant chemotherapy could improve survival in specific patients.

[Allogeneic hematopoietic stem cell transplantation for treatment of refractory and relapsed acute myeloid leukemia: outcomes and prognostic factors].

Objective: To evaluate the outcomes and prognostic factors of patients with refractory and relapsed acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The overall survival (OS) , disease free survival (DFS) , acute and chronic graft-versus-host disease (GVHD) , relapse rate (RR) , transplantation related mortality (TRM) and their related risk factors were analyzed retrospectively. Results: All the patients (median age 35 years, range 6 to 58) received myeloablative conditioning regimens. All patients had successful engraftment, and the median time of neutrophils engraftment was 14 days (range 9 to 25) . Of the patients who survived more than 100 days, the accumulative incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD (cGVHD) were 27.3% (95%CI 18.9%-36.3%) , 33.9% (95%CI 24.6%-43.5%) , respectively. Meanwhile, the accumulative incidence of extensive cGVHD was 9.3% (95%CI 4.5%-16.1%) . The 3-year OS, DFS, RR, and TRM was 45.0% (95%CI 34.6%-55.4%) , 45.0% (95%CI 34.8%-55.2%) , 36.6% (95%CI 26.9%-46.4%) and 19.7% (95%CI 12.4%-28.3%) respectively. Multivariate analysis revealed four independent risk factors: non remission status before transplantation[P=0.009, HR=2.21 (95%CI 1.22-4.04) ], WBC at diagnosis>50×10(9)/L[P=0.024, HR=2.11 (95%CI 1.11-4.02) ], donor age>35 years [P=0.031, HR=1.96 (95%CI 1.06-3.60) ]and without cGVHD[P=0.008, HR=0.38 (95%CI 0.18-0.78) ]. According to the risk factors before transplantation (non remission status, WBC at diagnosis>50×10(9)/L, donor age>35 years) , we then defined three subgroups with striking different OS at 3 years: no adverse factor (75.0%) ; one adverse factor (46.9%) ; two or three adverse factors (15.4%) (χ(2)=26.873, P<0.001) . Conclusion: Allo-HSCT is a promising and safe choice for patients with refractory and relapsed AML and relapse is the major cause of the transplantation failure. Disease status before transplantation, donor age, WBC at diagnosis and cGVHD are confirmed as prognostic factors for these patients who received allo-HSCT.

Analysis of high risk factors for endoscopic retrograde cholangiopancreatography biliary metallic stenting after malignant duodenal stricture SEMS implantation.

The aim of this study was to explore the success rates and high risk factors for endoscopic retrograde cholangiopancreatography (ERCP) biliary metallic stenting after self-expandable metallic stent (SEMS) implantation in patients with malignant duodenal stricture. A retrospective cohort study was conducted. Forty-two unresectable patients with malignant duodenal stricture who received endoscopic SEMS implantation between February 2012 and February, 2015 in the Department of Digestive Diseases of Xijing Hospital were enrolled in the study. These patients underwent subsequent ERCP biliary metallic stenting due to malignant biliary stricture. The clinical and iconography materials of these patients were retrospectively analyzed. ERCP biliary metallic stenting was successfully carried out on 71.4% of patients with previous malignant duodenal stricture SEMS implantation. In type 1 duodenal strictures 88% success rate of ERCP guided biliary decompression was obtained vs 18.2% success rate in Type 2 duodenal strictures. In both type 1 and 2 duodenal strictures of a length greater than 3.5 cm, ERCP was 44.4% successful vs 89% successful for strictures less than 3.5cm. Multiple regression analysis revealed that duodenal stricture length ≥3.5 cm (OR, 9.85; 95% CI, 1.21-79.88) and 80 or 90 mm duodenal stent (OR, 17.03; 95% CI, 1.99-145.81) were independent risk factors for the failure of ERCP (biliary drainage or biliary decompression) in the patients with previous SEMS implantation. Moreover, duodenal stents of 60 mm had a higher success rate of 88%, vs 18.2% in 80-90 mm stents. Nevertheless, the success rates of type III strictures were 100%, including synchronous and asynchronous implantation of SEMS implantation and ERCP biliary metallic stenting. For unresectable malignant duodenal stricture patients with SEMS implantation, subsequent ERCP biliary metallic stenting was safe and effective. The length of malignant duodenal stricture, longer duodenal stents and type II duodenal stricture were high risk factors for the failure of ERCP biliary metallic stenting.

Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo.

Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer.

Effects of rehabilitation management on gastric emptying function in older adults with diabetes.

The relationship between gastric emptying dysfunction and blood glucose concentration in elderly with type 2 diabetes mellitus was investigated, and the effect of rehabilitation exercise prescription training on gastric emptying in the geriatric diabetic patients was evaluated. A total of 160 older type 2 diabetic adults and 30 cases of non-diabetic patients were studied with regard to the gastric half emptying time (GET1/2) of solid meals radiolabelled with 99mTc. Eighty delayed gastric emptying diabetic patients were randomly divided into 4 four groups: rehabilitation exercise + mosapride group (N = 20), rehabilitation exercise group (N = 20), mosapride group (N = 20), and control group (N = 20). The level of blood glucose was measured every six months in a two-year follow-up. The solid GET1/2 of regulated blood glycemic control patients showed no statistically significant differences from non-diabetic patients (P > 0.05). However, the value for poor blood glycemic control patients exhibited significant statistical differences compared with both non-diabetic (P < 0.01) and regulated blood glycemic control group patients (P < 0.01). It showed that the gastric emptying time improved in the rehabilitation exercise group, mosapride group and rehabilitation exercise group + mosapride group after two years of treatment (P < 0.05). Fasting blood glucose in both rehabilitation exercise group and rehabilitation exercise + mosapride group was significantly decreased. Postprandial blood glucose in the rehabilitation exercise group, mosapride group, rehabilitation exercise group + mosapride group was significantly decreased. High blood glucose level can delay gastric emptying in older type 2 diabetic patients. Gastric emptying and blood glucose control affect each other. It was shown that appropriate rehabilitation exercise combined with prokinetic agent may improve gastric emptying in some geriatric type 2 diabetic patients and help control their blood glucose.

A common factor suppresses thickening in young women with malar area port wine stains and delays low density lipoprotein elevation: is it estrogen?

Port wine stains in the malar area of the face can develop thickening in early adult life. We began a study with a hypothesis that this thickening can be associated with elevation of low density lipoprotein. In a retrospective review, we divided 53 subjects with malar port wine stains into 4 groups, adults 25-39 years of age with thickening, that age group without thickening, adults 40+ years of age with thickening, and that age group without thickening. Low density lipoprotein levels in the subjects were compared to age and sex matched controls randomly selected from the general Dermatology clinic. The younger subjects with thickening demonstrated significantly higher low density lipoprotein levels than their controls (p .0082) and without thickening lower low density lipoprotein levels than their controls with great significance (p .00058). The subjects without thickening also consisted mainly of women. The low density lipoprotein levels in the older age groups, whether thickened or not, demonstrated no significant difference in low density lipoprotein levels between subjects and controls. This led to a new hypothesis that there is a factor in a subgroup of young adult women with malar port wine stains that suppresses thickening and delays the elevation of low density lipoprotein and that this factor might be estrogen. The implications of this hypothesis are that it could define a marker for a subset of the population that might be protected from the diseases associated with early elevation of low density lipoprotein and provide a source of cutaneous tissue for studying the basic science of this protection (although limited by cosmetic considerations). Future laboratory research to test the new hypothesis might include testing blood of women with malar port wine stains with or without thickening for estrogen and other sex hormones. It might also include skin biopsies to study receptors for estrogen, other sex hormones, and angiogenic factors in malar port wine stains with or without thickening. Future clinical research might include a long term prospective project to study the development of low density lipoprotein related diseases in women with malar port wine stains with or without thickening over years.