Virus reactivation in high-risk non-Hodgkin’s lymphoma patients after autologous CD34+-selected peripheral blood progenitor cell transplantation

CD34⁺-selected peripheral blood progenitor cells (PBPCs) may not only reduce contaminated tumor cells but also compromise immunologic reconstitution and increase incidence of infections after transplantation. We analyzed the incidence of virus reactivation in CD34⁺-selected PBPCs autologous transplantation. From December 2001 to December 2004, ten high-risk aggressive non-Hodgkin’s lymphoma (NHL) patients were enrolled in a program of high-dose chemotherapy plus autologous CD34⁺-selected PBPCs support. Viral screening studies, including clinical symptoms, physical examinations, hepatitis B virus (HBV)-DNA, cytomegalovirus (CMV)-polymerase chain reaction (PCR), rapid diagnosis of fluorescent antibody stain for herpes-simplex virus (HSV), and viral culture from blood, fluid or tissue were performed weekly during the first 3 months and then monthly for 1 year. Two of four patients (50%) who were HBV carriers developed HBV reactivation. The other two HBV carriers who received prophylactic lamivudine therapy did not develop HBV reactivation. Two patients (20%) developed cytomegalovirus (CMV) infection, and three patients (30%) developed HSV infection in total ten serum-positive patients. The possibility of virus reactivation might increase in NHL patients undergoing autologous CD34⁺-selected PBPC transplantation. Administering prophylactic antivirus therapy and closely following patient’s clinical viral complications should be considered.     

Development and validation of Cedars‐Sinai Health‐Related Quality of Life in Rheumatoid Arthritis (CSHQ‐RA) short form instrument

Objective

To develop an abridged version of the 33‐item Cedars‐Sinai Health‐Related Quality of Life in Rheumatoid Arthritis instrument (CSHQ‐RA) and test the validity and reliability of the abridged instrument.

Methods

Items from the original 33‐item, 5‐domain CSHQ‐RA were assessed using psychometric and regression analyses of survey responses from 274 patients with rheumatoid arthritis. Items were retained in the final instrument based on statistical analysis and evaluation by an expert panel. Test‐retest reliability, internal consistency, convergent and discriminant validity, and ceiling and floor effects were examined for the shortened CSHQ‐RA.

Results

Statistical analysis and expert assessment yielded an 11‐item instrument including questions in 4 domains. Test‐retest reliability and internal consistency were high and the instrument showed good convergent and discriminant validity.

Conclusion

The abridged CSHQ‐RA short form is a valid and reliable instrument that can be used to examine the impact of RA on patients' health‐related quality of life. Prospective validation in clinical trial settings is warranted.

     

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.     

Salmonella alters heparanase expression and reduces tumor metastasis

Salmonella causes salmonellosis, is a facultative anaerobe and is one of the common Gram-negative bacteria. Salmonella has anti-tumor potential and tumor-targeting activity. The heparin sulfate on cell surfaces can be cleaved by heparanase that is an endo-β-D-glucuronidase. Heparanase can destroy the extracellular matrix and is involved in tumor metastasis and angiogenic activity. Previously, Salmonella was demonstrated to inhibit tumor metastasis. It remains unclear whether Salmonella inhibits metastasis by regulating heparanase. The expression of heparanase in Salmonella-treated tumor cells was found to be decreased. Transwell and wound-healing assays demonstrated the inhibition of cell migration after Salmonella treatment. Salmonella was found to influence the levels of phosphate-protein kinase B (P-AKT) and phosphate-extracellular regulated protein kinases (P-ERK), which are involved in heparanase expression. Salmonella reduced the heparanase expression induced upregulating PERK and PAKT signaling pathways. The mice bearing an experimental metastasis tumor model was used to evaluate the anti-tumor metastatic effects of Salmonella. Compared with the control group, Salmonella significantly reduced the number of metastatic nodules and enhanced survival. The results of our study indicate that Salmonella plays a vital role in the inhibition of tumor metastasis through the downregulation of heparanase.     

Highly Improved Thermal Properties of Hydroxyl‐Containing Polymers via Modification by Benzoxazine Groups

Isocyanate functional benzoxazine (NCO‐4HBA‐a) is used for coupling with hydroxyl‐group‐containing molecules. Glycerol is used in a model reaction to study the urethane bonds formed between the NCO‐4HBA‐a and the glycerol's hydroxyl groups. The model supports a reaction between NCO‐4HBA‐a and poly(vinyl alcohol) (PVA), which leads to an improved char yield, determined by thermogravimetric analysis. Glycerol‐based benzoxazine is also an attractive benzoxazine synthesized from the products of biofuel production. Upon functionalization with benzoxazine and subsequent thermal treatment, the hydroxyl‐containing polymer gains thermal stability shown by improved char yield of polybenzoxazine cross‐linked PVA.

     

Myocardial tissue Doppler-based indexes to distinguish right ventricular volume overload from right ventricular pressure overload

The objective of this study was to develop tissue Doppler parameters that could be used to differentiate right ventricular (RV) volume overload from RV pressure overload. The RV-pressure-overload group consisted of 40 patients with severe pulmonary hypertension, and the RV-volume-overload group consisted of 40 patients who had an atrial septal defect without evidence of right-to-left shunt, significant pulmonary hypertension, or Eisenmenger's complex. Another 40 healthy subjects were enrolled and served as a control group. Routine echocardiography and tissue Doppler imaging were performed. RV myocardial performance index was determined based on data collected during tissue Doppler imaging over the lateral tricuspid annulus. In patients with RV pressure overload, tissue Doppler parameters showed characteristically lower systolic velocity over the tricuspid annulus (RV myocardial systolic wave [Sm]) and longer isovolumic relaxation time (RV-IVRT). Nevertheless, in patients with RV volume overload, RV-Sm increased significantly, but early-diastolic velocity over tricuspid annulus was relatively low. In conclusion, RV-MPI, RV-Sm/early-diastolic velocity over tricuspid annulus, and RV-IVRT/RV-Sm were all useful to differentiate RV pressure overload from volume overload, although RV-IVRT/RV-Sm was the best parameter, with excellent sensitivity and specificity.     

Residues Distal to the Active Site Contribute to Enhanced Catalytic Activity of Variant and Hybrid β-Lactamases Derived from CTX-M-14 and CTX-M-15

A variety of CTX-M-type extended-spectrum β-lactamases (ESBLs), including hybrid ones, have been reported in China that are uncommon elsewhere. To better characterize the substrate profiles and enzymatic mechanisms of these enzymes, we performed comparative kinetic analyses of both parental and hybrid CTX-M enzymes, including CTX-M-15, -132, -123, -64, -14 and -55, that are known to confer variable levels of β-lactam resistance in the host strains. All tested enzymes were susceptible to serine β-lactamase inhibitors, with sulbactam exhibiting the weakest inhibitory effects. CTX-M-55, which differs from CTX-M-15 by one substitution, A⁷⁷V, displayed enhanced catalytic activity (k_cat/K_m) against expanded-spectrum cephalosporins (ESCs). CTX-M-55 exhibits higher structure stability, most likely by forming hydrophobic interactions between A⁷⁷V and various key residues in different helices, thereby stabilizing the core architecture of the helix cluster, and indirectly contributes to a more stable active site conformation, which in turn shows higher catalytic efficiency and is more tolerant to temperature change. Analyses of the hybrids and their parental prototypes showed that evolution from CTX-M-15 to CTX-M-132, CTX-M-123, and CTX-M-64, characterized by gradual enhancement of catalytic activity to ESCs, was attributed to introduction of different substitutions to amino acids distal to the active site of CTX-M-15. Similarly, the increased hydrolytic activities against cephalosporins and sensitivity to β-lactamase inhibitors, clavulanic acid and sulbactam, of CTX-M-64 were partly due to the amino acids that were different from CTX-M-14 and located at both the C and N termini of CTX-M-64. These data indicate that residues distal to the active site of CTX-Ms contributed to their enhanced catalytic activities to ESCs.     

Can we predict pathologic complete response before surgery for locally advanced rectal cancer treated with preoperative chemoradiation therapy?

Background

Pathologic complete response has been proven to have oncological benefits for locally advanced rectal cancer treated with chemoradiation therapy. The aims of this study are to analyze and determine the factors to predict pathologic complete response for patients treated with preoperative neoadjuvant therapy.

Methods

Patients with biopsy-proven, locally advanced rectal cancer were treated neoadjuvantly followed by radical surgical resection. Tumors were re-assessed after completing chemoradiation, including pelvic magnetic resonance images, colonoscopic examination, and re-biopsy. The results of examination were compared with the final pathologic status.

Results

A retrospective chart review of 166 patients was conducted. Twenty-five patients (15.1%) had pathologic complete response after chemoradiation. The 5-year overall survival rates were better in the complete response group than the residual tumor group (91.1% vs. 70.8%; P?=?0.047), and there were also significant differences in the 5-year disease-free survival rates between these two groups (91.1% vs. 70.2%; P?=?0.027). The prediction rates for pathologic complete response by re-biopsy, magnetic resonance images, and colonoscopy were 21.4%, 33.3%, and 53.8%, respectively. In addition, when we further combine the results of colonoscopic findings and re-biopsy, the prediction rate for pathologic complete response reached 77.8% (P?=?0.009).

Conclusions

Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation.     

Performance Status Enhances the Selection of Treatment for Patients with Hepatocellular Carcinoma Within the Milan Criteria

Background

Performance status (PS) is closely linked with survival in patients with hepatocellular carcinoma (HCC). We investigated its impact on treatment strategy for small HCC(s).

Methods

A total of 360 and 362 HCC patients within the Milan criteria undergoing surgical resection (SR) and radiofrequency ablation (RFA), respectively, were prospectively enrolled. Patients were classified into PS 0 (n = 558) and PS ≥1 (n = 164) groups. Propensity score analysis was performed, and 168 and 35 matched pairs were selected from patients with PS 0 and ≥1, respectively.

Results

The SR group was younger and had a higher male-to-female ratio, higher prevalence of hepatitis B, lower prevalence of hepatitis C, better PS, better liver functional reserve, and larger tumor burden than the RFA group (all p < 0.05). Among patients with PS 0, the SR group was consistently younger, less cirrhotic, and had larger tumor burden (all p < 0.05). The long-term survival was comparable between SR and RFA group in patients with PS 0. After propensity score matching, SR provided significantly better long-term survival than RFA for patients within the Milan criteria classified as PS 0 (p = 0.016); the Cox proportional hazards model showed consistent results. There was no significant difference of overall survival between the SR and RFA group in patients with PS ≥1 before or after propensity score matching (both p > 0.05).

Conclusions

For HCC patients within the Milan criteria and classified as PS 0, SR provides a better long-term survival compared with RFA. Performance status may enhance treatment selection and stratify the risk of survival in these patients.