Effects of Facial Muscles Exercise on Mental Health: A Systematic Review.

Mental disorders are increasing worldwide. Previous research has reported an association between mental health and facial expressions. Face-to-face communication, specifically, is majorly affected when wearing face masks for a long time because of the COVID-19 pandemic. However, there have been no systematic reviews of facial muscles exercise intervention studies for mental health. Thus, evidence of their effect on mental health is unclear. This review aimed to evaluate the current evidence of the effectiveness of voluntary facial muscles exercise to improve some parameters of mental health. We implemented a systematic review of experimental studies (published between 2007 and 2018, 10 years before we decided to start this review). Of the 61,096 references screened, seven studies reported that facial muscles exercise may help to improve some parameters of mental health. Moreover, the study quality was assessed, and we extracted sub outcomes for mental health. Non-coherent results of seven experimental studies were included in this review. Voluntary facial muscles exercise may help improve depressive symptoms, mood, and reduce the level of chronic stress. However, due to the low quality of analyzed studies, further studies are needed to confirm the mental health benefits of a facial muscles exercise program.

Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma.

BACKGROUND & AIMS: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. METHODS: HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. RESULTS: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). CONCLUSIONS: A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. CLINICAL TRIAL NUMBER: UMIN000001299. LAY SUMMARY: Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.

[Effects of facial rehabilitation exercise on the mood, facial expressions, and facial muscle activities in patients with Parkinson's disease].

AIM: Facial expressions are often impaired in patients with Parkinson's disease (PD). Few studies have examined the effects of head and neck rehabilitation in patients with PD using a facial expression analysis. In the present study, to further elucidate the effects of facial rehabilitation exercise in patients with PD, a three-dimensional facial expression analysis with FaceReader™ and surface electromyography (EMG) were performed in order to assess the facial expressions and muscle activities, respectively. The effects of such exercises on the mood and mental health were also evaluated. METHOD: Twenty-one patients with PD (63.3±12.1 years) participated in the present study and were randomly assigned to an intervention group and non-intervention group. Facial rehabilitation exercise was performed for 60 minutes once a week for 12 weeks in the intervention group. GHQ-12, the facial expression analysis with FaceReader™, surface EMG, and the VAS scale for mood changes were used to evaluate the effects of the program. The results from both groups were compared. RESULTS: The results from eight patients in the intervention group and five in the non-intervention group were analyzed. FaceReader™ revealed a higher "Happy" index and lower "Sad" index in the intervention group than in the non-intervention group, and a significant interaction "Happy" index by an analysis of variance was noted between the two groups. EMG also showed increases in the activity of facial muscles in the intervention group. The subjects' mood improved after each facial rehabilitation exercise session. CONCLUSION: The results of the present study suggest that the facial rehabilitation exercise affected the mood, facial expression, and facial muscle activities in patients with PD and indicate that the expression analysis with the FaceReader™ and surface EMG are useful for evaluating the effects of facial rehabilitation exercise.

Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study.

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m2/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m2/cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study.

BACKGROUND: In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. METHODS: LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. FINDINGS: Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1-94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51-0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. INTERPRETATIONS: Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. FUNDING: Janssen Research & Development.

Treatment of malignant primary cardiac lymphoma with tumor resection using minimally invasive cardiac surgery.

BACKGROUND: Primary cardiac lymphoma (PCL) is extremely rare and progresses rapidly. The treatment of PCL has not yet been established. Unlike lymphoma that arises from other organs, PCL causes cardiovascular events. We report the complete remission (CR) of PCL after tumor resection using minimally invasive cardiac surgery (MICS) and chemotherapy. CASE PRESENTATION: The patient was a 79-year-old man who visited our hospital with chief complaints of weight loss and leg edema. A 40 × 30 mm mobile pedunculated tumor continuous with the right ventricular heart muscle was present in the right atrium upon echocardiography and extended cardiac surgery was difficult to perform. Tumor embolism-induced sudden death was prevented and a pathological diagnosis was obtained by making a 4-cm skin incision, and tumor resection with MICS was performed through a right fourth intercostal thoracotomy with a cardiopulmonary system. The histopathological diagnosis was diffuse large B cell malignant lymphoma. Eight cycles of postoperative rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were performed. Three years after surgery, the tumor was not visible on imaging and CR was maintained. CONCLUSIONS: This case highlights that tumor resection using MICS is effective for avoiding the risk of sudden death. This technique was useful for the diagnosis and treatment of a malignant cardiac tumor in an elderly patient that required a difficult extended cardiac surgery.

Bortezomib-based therapy for transplant-ineligible East Asian patients with newly diagnosed mantle-cell lymphoma.

INTRODUCTION: This subgroup analysis of the LYM-3002 Phase III study (NCT00722137) investigated whether substituting bortezomib for vincristine in frontline R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy could improve outcomes in East Asian patients with newly diagnosed mantle-cell lymphoma (MCL). MATERIALS AND METHODS: A total of 121 East Asian patients from China, Taiwan, Japan, and the Republic of Korea with stage II-IV MCL who were ineligible or not considered for stem-cell transplantation were enrolled to six to eight 21-day cycles of R-CHOP or VR-CAP (R-CHOP with bortezomib replacing vincristine). RESULTS: The primary end point was progression-free survival. After a median follow-up of 42.4 months, median progression-free survival in East Asian patients was 13.9 (R-CHOP) versus 28.6 (VR-CAP) months (HR 0.7, P=0.157; 43% improvement with VR-CAP). Secondary end points (R-CHOP vs VR-CAP), including complete response rate (47% vs 63%), duration of complete response (median 16.6 vs 46.7 months), and treatment-free interval (median 21 vs 46.5 months), were improved with VR-CAP. VR-CAP was associated with increased but manageable toxicity. The most frequent adverse events were hematologic toxicities. CONCLUSION: VR-CAP was effective in East Asian patients with newly diagnosed MCL, and could be considered for patients in whom stem-cell transplantation is not an option.

[The effective of facial exercises on the mental health in elderly adults].

AIM: Although it is well documented that exercising is good for the mental health and cognitive function as well as the physical condition in elderly people, exercising is difficult in elderly individuals with a low motor function. To develop an exercise program targeting elderly individuals unsuited for whole-body exercises, we assessed the effects of facial exercises on the mental health in healthy elderly people. METHODS: Community-dwelling older adults (N = 75, age range = 65-87 years) were randomly divided into a facial exercises group and a wait-listed control group. A facial exercises program of 30 min was given twice a week for 12 weeks. This program consisted of rhythmic facial movement, muscle stretching, facial yoga, and Tanden breathing. The GHQ-12 for mental health were administered to both groups before and after the 12-week study period. In addition, the facial expression and tongue muscle power were measured. RESULTS: Fifty-three participants completed the protocol. In the intervention group, the GHQ-12, facial expression, and tongue muscle power improved post-intervention. CONCLUSIONS: These results suggest that facial exercises are effective in improving the mental health, facial expression, tongue muscle power of elderly people, and that exercises may be useful as a therapeutic modality in this population.

The standard international prognostic index for predicting the risk of CNS involvement in DLBCL without specific prophylaxis.

Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1.3, 4.6, 8.8, and 12.7% in the low-, low-intermediate-, high-intermediate-, and high-risk groups, respectively (p <.001). This result is comparable with that of the CNS-IPI. Patients with breast involvement tended to have lower risk according to the standard IPI but showed frequent CNS involvement, similar to patients with testis involvement. The standard IPI is also a useful predictor of CNS involvement. Patients with breast/testis involvement would be candidates for prophylaxis regardless of the standard IPI risk.

Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP versus R-CHOP in the phase 3 LYM-3002 study.

In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7 versus 14.4 months with R-CHOP; P<0.001). This post-hoc analysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAP versus R-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9 versus 19.8 months; partial response: 17.1 versus 11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluable versus 26.6 months; partial response: 35.3 versus 24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low-and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of this post-hoc analysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low- and intermediate-risk MIPI. LYM-3002 ClinicalTrials.gov: NCT00722137.

[Effectiveness of Dexrazoxane for Extravasation of Anthracycline Antitumor Antibiotics - Reporting Measures Developed against Extravasation in the Hospital].

Dexrazoxane(DXZ)is a drug used for treating extravasation(EV)of anthracycline antitumor antibiotics based on 2 of its mechanisms of action through Topo II. In Japan, it has been used in approximately 150 patients as of January 2016, but there is no detailed report. Three DXZ treatments were carried out for 2 cases in our facilities. One case involved a patient's right forearm while 2 cases occurred involved the left and right forearms of each of the patients, and both were Grade 2(CTCAE v4.0). The EV healed in all cases, and surgical procedures were not needed. Moreover, chemotherapy was performed without extending the treatment period. One year 8 months after administration there was no recurrence in both cases, and skin disorders did not develop. In our hospital, DXZ is managed based on the regimen as well as the anticancer agents, and administration within 6 hours from extravasation was made possible by the cooperation of pharmaceutical wholesalers. Nurses and pharmacists who engage in chemotherapy are encouraged to participate in the study sessions of the hospital, it has been the effort to learn the day-to-day knowledge and technology. DXZ is effective in treating the EV of anthracycline antitumor antibiotics and may be well tolerated. To properly use DXZ by integrating these cases, it is necessary to verify its effectiveness and safety.

Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study.

BACKGROUND: There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). METHODS: We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL. RESULTS: With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. CONCLUSIONS: Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma.

BACKGROUND: The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma. METHODS: In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. RESULTS: After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group. CONCLUSIONS: VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.).

Meta-analysis of epoetin beta and darbepoetin alfa treatment for chemotherapy-induced anemia and mortality: Individual patient data from Japanese randomized, placebo-controlled trials.

Erythropoiesis-stimulating agents (ESA) reduce the need for transfusions and improve the quality of life in patients receiving chemotherapy, but several clinical trials have suggested that ESA might have a negative impact on survival. To evaluate the efficacy and safety of ESA, epoetin beta and darbepoetin alfa, including their impact on overall survival and thromboembolic events, we conducted an individual data-based meta-analysis of three randomized, placebo-controlled trials studying Japanese patients with chemotherapy-induced anemia. All trials were conducted in compliance with Good Clinical Practice. A total of 511 patients with solid tumor or lymphoma (epoetin beta or darbepoetin alfa, n = 273; placebo, n = 238) were included. The ESA significantly reduced the risk of transfusion (relative risk, 0.47; 95% confidence interval, 0.29-0.76). No significant effect of the ESA on overall survival was observed (unadjusted hazard ratio, 1.00; 95% confidence interval, 0.75-1.34). A prespecified subgroup analysis showed no strong interaction between the baseline hemoglobin concentration and the effect of ESA on overall survival. Among the ESA-treated patients, the highest hemoglobin achieved during the treatment period in each patient had no impact on mortality. No increase in thromboembolic events was observed in the ESA-treated patients (0.7% vs 1.7% placebo). The ESA reduced the risk of transfusion without a negative impact on the survival of patients with chemotherapy-induced anemia.

Kinetics of peripheral hepatitis B virus-specific CD8+ T cells in patients with onset of viral reactivation.

BACKGROUND: Patients with resolved hepatitis B virus (HBV) infection undergoing chemotherapy or immunosuppressive therapy are potentially at risk of HBV reactivation. However, it remains unclear how liver disease develops after HBV reactivation. To compare the host immune response against HBV, we performed immunological analyses of six HBV reactivation patients. METHODS: The numbers of peripheral HBV-specific CD8+ T cells were investigated longitudinally in six HLA-A2- and/or A24-positive patients with HBV reactivation. In addition, 34 patients with resolved HBV, 17 patients with inactive chronic hepatitis B (ICHB), 17 patients with chronic hepatitis B (CHB) and 12 healthy controls were analyzed. The number and function of HBV-specific CD8+ T cells were assessed by flow cytometry using tetramer staining and intracellular IFN-γ production. Furthermore, the numbers of CD4+ CD25+ or CD4+ Foxp3+ T cells and serum inflammatory cytokine levels were analyzed. RESULTS: The frequency of HBV-specific CD8+ T cells was significantly increased in HBV reactivation patients compared with ICHB and CHB patients. In addition, the number of HBV-specific CD8+ T cells was increased in resolved HBV patients compared with ICHB patients. PD-1 expression was decreased in HBV reactivation patients compared with ICHB and CHB patients. The numbers of HBV-specific CD8+ T cells and CD4+ CD25+ or CD4+ Foxp3+ T cells were negatively correlated following onset of HBV reactivation. CONCLUSIONS: During HBV reactivation, the frequency of HBV-specific CD8+ T cells increased even though the administration of immunosuppressive drugs and interactions with CD4+ regulatory T cells may be important for the onset of liver disease.

Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era.

Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further.

Prognostic analysis and a new risk model for Hodgkin lymphoma in Japan.

The Japan Clinical Oncology Group conducted two multicenter phase II trials in 200 patients with advanced Hodgkin lymphoma (HL) in the 1990s. Among 181 patients whose histopathological specimens were available and reviewed by 6 hematopathologists, 167 (92.3%) were diagnosed with HL. Five-year overall survival (OS) among these 167 patients was 88.3%, including 89.2% among nodular sclerosis and 82.2% among mixed cellularity cases. International prognostic score was not closely associated with OS. Seven unfavorable prognostic factors for OS on univariate analysis were male, B symptoms, clinical stage of III or IV, elevated serum LDH, elevated alkaline phosphatase, elevated beta2-microglobulin, and pathological subtype (mixed cellularity and lymphocyte depletion). On multivariate analysis, male [HR 3.30 (95% CI 1.15-9.52, p = 0.027)] and elevated serum LDH [HR 2.41 (95% CI 1.07-5.43, p = 0.034)] were independent factors for OS. Based on these prognostic factors, the 5-year OS was 95.7% in the low-risk group (no adverse factor), 87.9% in the intermediate-risk group (1 adverse factor) and 73.3% in the high-risk group (2 adverse factors). This simple prognostic model for HL warrants further validation studies.

[Malignant lymphoma].

18-Fluoro-deoxyglucose positron emission tomography (FDG-PET) has become widely used in the management of patients with malignant lymphomas. FDG-PET has been evaluated in pretreatment staging, restaging, monitoring during therapy, and posttherapy surveillance. The Ann Arbor staging system was initially based on physical examination and bone marrow evaluation, but more recently, CT scans or 67gallium scintigraphy have been incorporated. FDG-PET may provide complementary information to conventional staging methods, and may be of particular value prior to therapy for patients who appear to have stage I or II disease and for whom radiation therapy is being considered. FDG-PET has technical limitations, variability of FDG avidity among different lymphoma histologic subtypes, and in a large number of etiologies shows false-negative and false positive results. Most studies of FDG-PET involve patients with Hodgkin's disease or diffuse large B-cell lymphoma. FDG PET in lymphoma is being incorporated into the response assessment in lymphoma as published by the Imaging Subcommittee of International Harmonization Project in Lymphoma. New guidelines, the Revised Response Criteria for Malignant Lymphoma, are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. They should reduce the variability among studies. Standardized definitions of end points are provided. Standardized FDG-PET will hopefully lead to improved outcome for patients. PET as a biomarker has the potential to change the current model of drug development.

[A case of colon cancer with reversible posterior leukoencephalopathy syndrome following 5-FU and oxaliplatin (FOLFOX regime)].

We report a rare case of reversible posterior leukoencephalopathy syndrome (RPLS) induced by 5-FU and oxaliplatin (FOLFOX regime). A 35-year-old woman with ileus was diagnosed with sigmoid cancer Stage IV (T4N4M0P2H0), and excision of the sigmoid colon, and left ureteroureteral anastomosis was performed. Postoperative chemotherapy with FOLFOX4 was performed. Complications of hypertension were seen on day 6, and convulsions on day 11 after chemotherapy. Headache and visual disturbance were also complications. MRI of the brain revealed bilateral high signal intensities of posterior lobes on T2 weighted and FLAIR images without enhancement. The patient was treated with antihypertensive therapy and anticonvulsive therapy. Her symptoms entirely disappeared, including the bilateral posterior lesions on MRI after two weeks. This report would suggest that medical oncologists should be aware that multidrug chemotherapies may increase the risk of fatal neurological complications like RPLS.

[Two cases of stomach primary diffuse large B cell lymphoma remitted by Helicobacter pylori eradication therapy].

CASE 1: The patient was a 71-year-old woman who came to our hospital for epigastric checkup. Upper gastrointestinal endoscopy showed an ulcerative lesion. Because Helicobacter pylori was positive, eradication therapy was given. As a result of biopsy, a diagnosis of diffuse large B cell lymphoma was made and she was introduced to our department. The lesion showed improvement with upper gastrointestinal endoscopy after eradication therapy, and no lymphoma cells were confirmed. She has been doing well without a recurrence. CASE 2: The patient was a 49-year-old man who had an anomaly noted with upper gastrointestinal endoscope. Then he was introduced to our hospital. Helicobacter pylori eradication therapy was performed because MALT lymphoma was suspected by a previous hospital. The only evidence of chronic gastritis was revealed with upper gastrointestinal endoscope at our hospital, but no lymphoma cells. As we reviewed a specimen again before Helicobacter pylori eradication therapy, the diagnosis was diffuse large B cell lymphoma because lymphoma cells were large, the MIB1 index was high, and Bcl-6 was positive. He has been doing well without a recurrence. As for a treatment of localized diffuse large B cell lymphoma, chemo-radiotherapy has generally been performed. However, we reported here two cases of gastric diffuse large B cell lymphoma regression that were confirmed after Helicobacter pylori eradication therapy, and CR was maintained without a recurrence.