Are dynamic or fixed FDG-PET measures of disease of greater prognostic value in patients with relapsed/refractory diffuse large B-cell lymphoma undergoing autologous haematopoietic stem cell transplantation?

Positron emission tomography (PET) response assessment using the Deauville score has prognostic utility in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem-cell transplantation (ASCT). Improved predictive methods are required to identify patients with poor outcomes who may be better considered for other salvage options. We investigated the prognostic value of mean tumour volume (MTV) and maximum standardised uptake value (SUVmax) at pre-salvage and pre-ASCT time-points, and the quantitative changes between scans (∆MTV and ∆SUVmax). One hundred and twenty-five patients with R/R DLBCL underwent salvage immunochemotherapy and ASCT: 80 patients had pre-salvage PET and 90 had pre-ASCT PET available. With a median follow-up of 5.6 years, 5-year progression-free survival (PFS) and overall survival (OS) were 52% and 65%, respectively. For patients with PET-positive residual disease after salvage therapy, pre-ASCT MTV was a significant negative prognosticator for PFS (HR 1.19 per 100 ml, p < 0.001) and OS (HR 1.78 per 100 ml, p < 0.001). Similarly, pre-ASCT SUVmax was negatively associated with PFS (HR 1.08, p < 0.001) and OS (HR 1.08, p < 0.001). Notably, pre-salvage MTV and SUVmax and ∆MTV and ∆SUVmax were not associated with PFS or OS. In conclusion, pre-ASCT MTV and SUVmax appear to be of greater predictive value than the degree of response. Potential application may exist for PET-directed management of R/R DLBCL patients.     

High maximum standard uptake value (SUVmax) on PET scan is associated with shorter survival in patients with diffuse large B cell lymphoma

FDG-PET scan plays an important role in response assessment in diffuse large B cell lymphoma (DLBCL). In this study, we evaluated the prognostic value of maximum standard uptake (SUVmax) on pretreatment PET scan in DLBCL. Among 169 patients with DLBCL newly diagnosed and treated with R-CHOP between 2003 and 2008, 110 patients who had undergone pretreatment PET scan in single institute using an identical protocol were reviewed and analyzed. SUVmax at the predominant lesion on PET scan and other patient characteristics were evaluated for their association with complete response (CR) rate, overall survival (OS) and progression-free survival (PFS). The median SUVmax was 18.1 (2.0–36.4). There was no significant association between high SUV and other characteristics with the exception of PS ≥ 2 and Ki-67. Multivariate analysis revealed the independent association between high SUVmax and lower CR rate. The 3-year PFS rates in patients with SUV < 30 and those with SUV ≥ 30 were 78 and 51%, respectively (p = 0.06). The 3-year OS rates were 86 and 71%, respectively (p = 0.03). Multivariate analysis revealed that high SUVmax is a significant poor prognostic factor for both PFS and OS, independent of IPI. We showed the important prognostic value of pretreatment SUVmax of PET scan in DLBCL.     

PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial

The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I–IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90–91%; P = 0·76) and OS (97–99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3·8; 95% confidence interval 2·4–6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.     

Prognostic impact of interim positron emission tomography in mantle cell lymphoma patients treated with frontline R-CHOP

Although ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end-of-treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five-year overall survival (OS) [hazard ratio (HR) 7·84, P < 0·0001] and poor five-year progression-free survival (PFS) (HR 3·34, P < 0·0001). OS and PFS were more favourable in the order early metabolic responder (iPET^neg → ePET^neg), delayed responder (iPET^pos → ePET^neg), loss-metabolic responder (iPET^neg → ePET^pos), and never-metabolic responder (iPET^pos → ePET^pos). In the autologous haematopoietic stem cell transplantation (auto-HSCT)-fit subgroup, OS was more favourable in the order early metabolic responders, delayed metabolic responders, and non-metabolic responders, with a marginal trend toward statistical significance (HR 3·41, P = 0·051), and PFS was significantly superior in early metabolic responders (HR 4·43, P = 0·002). In a group that was ineligible for auto-HSCT, OS and PFS were significantly superior in early metabolic responders. Our results suggested that iPET is of prognostic value and an independent predictor of survival in MCL patients receiving frontline R-CHOP. Therefore, prospective clinical trials of iPET-guided treatment strategies for these patients are warranted.     

Prognostic implications of BAX protein expression and microsatellite instability in all non-metastatic stages of primary colon cancer treated by surgery alone

Purpose  This study examined whether the apoptosis-related protein, BAX, or the microsatellite-instability phenotype provide prognostic information in patients with resected colon cancer. Methods  A total of 371 stage I–III patients that previously underwent radical surgery were included (mean follow-up 51.8 months). BAX expression was examined by immunohistochemical staining; high-frequency microsatellite instability (MSI+) was determined by assessing the specific marker, BAT26, using single-strand conformation polymorphism (SSCP)-based analysis. Results  High BAX expression was found in 66.4% of patients. MSI+ tumors were observed in 14.8% of 344 patients. Univariate analysis showed that unlike MSI, low BAX expression was significantly correlated with poor disease-specific overall survival (OS) in stages I–III (p = 0.04). Multivariate subgroup analyses revealed that unlike MSI, low BAX was an independent predictor for OS in stage II (p = 0.009); however, in stages I or III, BAX or MSI were not independent predictors of OS. Conclusions  In stage II colon cancer treated with surgery alone, BAX protein expression may be a predictor for prognosis. Oliver Nehls and Holger G. Hass contributed equally to this work.     

Tandem high-dose therapy in relapsed and refractory B-cell lymphoma: results of a prospective phase II trial of myeloablative chemotherapy,followed by escalated radioimmunotherapy with <Superscript>131</Superscript>I-anti-CD20 antibody and stem cell rescue

A phase II trial evaluated safety, feasibility and efficacy of a sequential tandem approach combining myeloablative BEAM chemotherapy and autologous stem cell transplantation (ASCT) with myeloablative radioimmunotherapy (HD-RIT), with ¹³¹I-anti-CD20 antibody (¹³¹I-rituximab), followed by a second ASCT in patients with relapsed or refractory CD20+ B-cell lymphoma. According to protocol, 16 patients with relapsed (n = 14) and refractory (n = 2) CD20+ B-cell lymphoma received salvage therapy with rituximab and Dexa-BEAM, followed by BEAM (HD chemotherapy) and high-dose myeloablative radioimmunotherapy 2–6 months after BEAM. Nine of 16 patients received HD-RIT; seven patients were excluded before HD-RIT because of toxicity or progressive disease. Disease histologies were follicular lymphoma (FL) grades 1 and 2 (n = 4), transformed follicular (FL 3b; n = 6), diffuse large B-cell (DLBCL; n = 4), mantle cell (n = 1) and marginal zone lymphoma (n = 1). After a median follow-up of 50.4 months for OS and 39.7 months for progression-free survival (PFS), estimated 4-year OS and PFS were 67% and 64%, respectively. The estimated 4-year OS and PFS for patients with FL were 80% and 78%, respectively. Toxicity was significant, including one fatal outcome due to pneumonitis. Tandem transplants consisting of HD chemotherapy followed by HD-RIT with ¹³¹I-coupled anti-CD20 are manageable and effective but toxic treatment modalities for relapsed poor prognosis CD20+ B-NHL.     

Post-autologous stem cell transplantation administration of rituximab improves the outcome of patients with aggressive B cell non-Hodgkin’s lymphoma

The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin’s lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.     

Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Chinese patients

The objective of this study is to evaluate the long-term efficacy and safety of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in Chinese patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The study comprised a retrospective analysis of patients treated at a single center. Patients received four to six infusions of rituximab (375 mg/m² per dose) on day 1 of each cycle of CHOP chemotherapy. CHOP was initiated on day 3 of each cycle; cycles were repeated at 21-day intervals. A total of 82 patients with a median age of 45 years (range 18–76 years) was included. The overall response (OR) and complete response (CR) rates were 90.2 and 70.7%, respectively. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 56.4 ± 8.3% and 74.1 ± 7.4%, respectively. Patients with International Prognostic Index (IPI) scores ≤2 had significantly higher OR, CR, PFS, and OS rates (p = 0.01, p = 0.02, p = 0.01, p < 0.001, respectively) compared with patients with IPI scores >2. The hematologic toxicity was mild. Five patients with a history of chronic hepatitis B experienced a reactivation of viral hepatitis. The rituximab–CHOP combination was effective and well tolerated in Chinese patients with newly diagnosed DLBCL. This study was conducted in accordance with the Chinese Good Clinical Practice (GCP), including ethical approval.     

Ligasure? versus diathermy hemorrhoidectomy under spinal anesthesia or pudendal block with ropivacaine: a randomized prospective clinical study with 1-year follow-up

Purpose  We evaluate the safety and efficacy of a spinal anesthesia with lidocaine versus a local anesthesia of pudendal block with ropivacaine combined with intravenous sedation in the hemorrhoidectomy procedure and also we compared the short- and long-term efficacy of conventional diathermy versus Ligasure™ diathermy hemorrhoidectomy. Methods  Seventy-four patients of grade III or IV hemorrhoids were randomized to conventional diathermy hemorrhoidectomy under spinal (n = 19) or local anesthesia (n = 18) and Ligasure™ diathermy hemorrhoidectomy under spinal (n = 17) or local anesthesia (n = 20). Time of follow-up was 12 months. Results  Patients operated under local anesthesia had less pain (p < 0.01), less analgesic requirements (p < 0.001), shorter hospital stay (p < 0.01), and less postoperative complications (p < 0.05). A shorter operating time (p < 0.001) and less complications at 4 months postoperatively (p < 0.05) was observed in the Ligasure™ group, but differences at 12 months were not found. Conclusions  Hemorrhoidectomy under local anesthesia with pudendal block with ropivacaine and sedation reduced postoperative pain, analgesic requirements, and postoperative complications, and can be performed as day-case procedure. Ligasure™ diathermy hemorrhoidectomy reduced operating time and was equally effective than conventional diathermy in long-term symptom control.     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Pre-treatment metabolic tumour volume and total lesion glycolysis are superior to conventional positron-emission tomography/computed tomography variables for outcome prediction in patients with newly diagnosed multiple myeloma in clinical practice

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are positron-emission tomography / computed tomography (PET/CT) variables for predicting multiple myeloma’s (MM) outcome. We retrospectively investigated and compared the predictive value of MTV, TLG and high-risk PET/CT variables in clinical practice in 185 patients with newly diagnosed symptomatic MM. High-risk PET/CT findings were defined as the presence of at least one of the following: more than three focal lesions, maximum standardised uptake value (SUV_max) >4·2 and extramedullary disease. MTV was defined as the volume of myeloma lesions visualised on PET/CT with SUV ≥ 2·5. TLG was calculated as the sum of the product of the average SUV and MTV of all lesions. The mortality prediction optimal cut-off values for MTV and TLG were 56·4 cm³ and 166·4 g, respectively. High-burden MTV (≥56·4 cm³), TLG (≥166·4 g) and high-risk PET/CT findings differed significantly in progression-free survival (PFS) and overall survival (OS). High-burden MTV and TLG findings also predicted survival outcomes in young patients (age <75 years) and patients with high-risk chromosomal abnormalities. High-burden MTV and TLG independently predicted both worse PFS and OS. Pre-treatment MTV and TLG independently predicted survival outcomes in clinical practice and may be more useful than high-risk PET/CT variables.     

The prognostic factors of stage IV colorectal cancer and assessment of proper treatment according to the patient’s status

Background and aims Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV. The majority has non-curative metastases, and their chances of survival are pitiful. This study evaluated the prognostic factors of survival and the access to the effective treatment in accordance with patients. Materials and methods We retrospectively analyzed 503 patients for demographics, tumor characteristics, the treatment modality, and the survival outcome. Curative operation was performed in 127 patients and palliative operation in 376 patients. Results For the curative operation group, the 5-year survival rate was 34.5%, and the prognostic factors of survival and recurrence were male gender (p = 0.003, 0.009), pathologic N stage (p < 0.001, p = 0.002), and perineural invasion (p = 0.003, p = 0.026), respectively. For the non-curative operation group, the 5-year survival rate was 0%, and the median survival duration was 16.5 months. The potential predictors of survival for the palliative operation group were carcinoembryonic antigen level (p = 0.013), differentiation of tumor (p = 0.011), resection of primary tumor (p < 0.001), and chemotherapy (p < 0.001). But for the 131 patients with asymptomatic incurable disease, only chemotherapy was related to survival (p < 0.001). Conclusions The potential predictors of survival for curative stage IV colorectal cancer were male gender, pathologic N stage, and perineural invasion. Resection of the primary tumor and chemotherapy showed benefit for the incurable patients. But for the asymptomatic incurable patients, only chemotherapy prolonged the survival. This study was presented at the 21st Biennial Congress of International Society of the University of Colon and Rectal Surgeons held in Istanbul, Turkey in June 2006.     

Parameters related to a positive test result for FDG PET(/CT) for large vessel vasculitis: a multicenter retrospective study

The purpose of this study was to identify clinical and laboratory parameters that may improve the effectiveness of the use of fluorodeoxyglucose positron emission tomography (¹⁸ F-FDG PET)(/CT) for diagnosing large vessel vasculitis (LVV), and secondarily to assess the contribution of ¹⁸ F-FDG PET/CT in finding other diagnoses for patients without signs of LVV on the scan. A multicenter retrospective study of ¹⁸ F-FDG PET(/CT) scans performed between January 2000 and December 2009 for clinical suspicion of LVV was conducted. A total of 304 ¹⁸ F-FDG PET(/CT) scans were included, of which 62 (20%) were positive and 242 (80%) were negative for LVV. Univariate analysis showed that patients with a positive scan were older (65.9 ± 13.4 versus 58.6 ± 16.5 years, p = 0.002), were more frequently female (76% versus 55%, p = 0.002), more often had a history of temporal arteritis (10% versus 3%, p = 0.044), less frequently had artralgia (31% versus 67%, p = 0.000), and had higher thrombocyte counts (434 ± 161 versus 373 ± 168 × 10⁹/l, p = 0.049) and a higher erythrocyte sedimentation rate (ESR) (72.6 ± 31.0 versus 51.4 ± 30.5 mm/h, p = 0.001) than patients with a negative scan. In the multivariate analysis, only artralgia (OR 0.091; 95% CI 0.023–0.366) and ESR (OR 1.024; 95% CI 1.002–1.046) remained statistically significant predictors. The presence of artralgia is a statistically significant negative predictor and an elevated ESR a statistically significant positive predictor of LVV showing up on ¹⁸ F-FDG PET(/CT). A reliable prediction of the outcome of the scan, based on these two parameters, is not possible however. ¹⁸ F-FDG PET(/CT) allows early diagnosis of LVV and may discover occult inflammatory or neoplastic disorders.     

Anti-agalactosyl IgG antibody in ankylosing spondylitis and psoriatic arthritis

Anti-agalactosyl IgG antibody (anti-Gal(0) IgG) has been regarded as a useful serological marker for rheumatoid arthritis (RA). It is unknown whether it is also elevated in serum and implicated in the pathogenesis of joint inflammation in seronegative spondyloarthropathy (SpA) such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Sera were collected from 43 patients with AS or PsA with axial joint involvement, 22 patients with RA, and 25 healthy normal individuals for the detection of anti-Gal(0) IgG with a cup-type lectin enzyme immunoassay (Eitest CA^.RF). The disease activity of the AS/PsA was evaluated by Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), the serum C-reactive protein (CRP) and IgA were measured by nephelometry, and erythrocyte sedimentation rate (ESR) was measured by Westergren’s method. The median titers of anti-Gal(0) IgG were significantly elevated in patients with RA (167.85, 15.73∼797.58 AU/mL) and AS/PsA (186.15, 34.71∼651.19 AU/mL), compared to those of the normal controls (13.04, 12.00∼202.43 AU/mL). The titers of the anti-Gal(0) IgG in patients with AS/PsA were correlated to the BASDAI scores (r ² = 0.422, SEE = 1.443, p < 0.001) and serum CRP (r ² = 0.345, SEE = 2.434, p < 0.001) but not to IgA (r ² = 0.0259, SEE = 126.30, p < 0.001) or ESR (r ² = 0.171, SEE = 31.053, p = 0.0059). Collectively, the anti-Gal(0) IgG is elevated and vaguely correlated with the disease activity of AS/PsA although its titers in these patients were erratic. The result of the present investigation has suggested that anti-Gal(0) IgG may be more ubiquitously present in inflammatory arthritides including RA or SpA.     

Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study

Low baseline NK-cell counts (NKCCs) in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a poor prognosis. The REMARC phase III trial (NCT01122472) showed that lenalidomide maintenance prolonged PFS in rituximab–chemotherapy responders. We conducted a REMARC ancillary study analysing the impact of lenalidomide maintenance on the prognostic value of low NKCCs. Blood samples from 335 elderly French patients enrolled in the REMARC trial were analysed by flow cytometry to obtain NKCCs at diagnosis (n = 220), at randomization (n = 186) and/or six months after randomization (n = 184). Baseline NKCCs < 100 cells/μl were associated with shorter PFS and OS (HRs = [2.2 (1.4, 3.3), p < 0.001] and [2.8 (1.7, 4.5), p < 0.001], respectively), independently of aaIPI. In a competing risk analysis, low NKCCs at baseline were associated with a higher risk of relapse/progression (p = 0.0025), but not of death without progression (p = 0.33). Lenalidomide did not affect the prognosis value of low baseline NKCCs (p  = 0.6349). Similar results were obtained for low NKCCs at randomization. Our results demonstrate that low NKCCs at baseline and post rituximab–chemotherapy are robust prognostic factors in DLBCL and reveal that lenalidomide has no impact on this parameter. Other therapeutic strategies aiming at improving NK-cell function could improve outcomes in DLBCL.     

Autologous hematopoietic stem cell transplantation—what determines the outcome: an experience from North India

Limited information is available from developing countries about complications, pattern of infections, and long-term outcome of patients following high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ASCT). Between April, 1990 and December 2009, 228 patients underwent ASCT. Patients’ median age was 48 years, ranging from 11 to 68 years. There were 158 males and 70 females. Indications for transplant included multiple myeloma, n = 143; lymphoma, n = 44 (Hodgkin’s, n = 25 and non-Hodgkin’s, n = 19); leukemia, n = 22; and solid tumors, n = 18. Patients received HDCT as per standard protocols. Following ASCT, 175 (76.7%) patients responded; complete, 98 (43%); very good partial response, 37 (16.2%); and partial response, 40 (17.5%). Response rate was higher for patients with good Eastern Cooperative Oncology Group (ECOG) performance status (0–2 vs. 3–4, p < 0.001), pretransplant chemo-sensitive disease (p < 0.001) and those with diagnosis of hematological malignancies (p < 0.003). Mucositis, gastrointestinal, renal, and liver dysfunctions were major nonhematologic toxicities, 3.1% of patients died of regimen-related toxicities. Infections accounted for 5.3% of deaths seen before day 30. At a median follow-up of 66 months (range, 9–234 months), median overall (OS) and event-free survival (EFS) were 72 months (95% CI 52.4–91.6) and 24 months (95% CI 17.15–30.9), respectively. For myeloma, OS and EFS were 79 months (95% CI 52.3–105.7) and 30 months (95% CI 22.6–37.4), respectively. Pretransplant good performance status and achievement of significant response following transplant were major predictors of survival. Our analysis demonstrates that such procedure can be successfully performed in a developing country with results comparable to developed countries.     

Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial

The aim of this study was to investigate the effects of ALC treatment on cognitive functions in patients with severe hepatic encephalopathy. This was a randomized, double-blind, placebo-controlled study. 61 patients with severe hepatic encephalopathy were recruited to the study. The 2 groups received either 2 g ALC twice a day (n = 30) or placebo (n = 30) for 90 days. Clinical and laboratory assessment, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. At the end of the study period, between the 2 groups we observed a significant difference in Everyday Memory Questionnaire −23.9 vs 4.4 (p < 0.001), Logical Memory (Paragraph recall) test 22.3 vs 0.7 (p < 0.001), Trail Making Test A −7.5 vs −2.6 (p < 0.001), Trail Making Test B −10.5 vs −3.1 (p < 0.001), Controlled Oral Word Association Test 4.2 vs 0.5 (p < 0.001), Hooper test 2.6 vs 0.1 (p < 0.05), Judgement of line orientation 2.8 vs 0.3 (p < 0.001), Digit Cancellation time −24.5 vs −2.4 (p < 0.001), NH₄⁺ 30.5 vs 13.5 (p < 0.001), prothrombin time 2 vs 2.4 (p < 0.05), alanine transaminase −10.7 vs −13.6 (p < 0.001). 88% of patients treated with ALC vs 72% of patients treated with placebo showed a significant improvement in EEG. The improvement of cognitive deficits, the reduction of ammonia, and the modification of EEG in patients treated with ALC suggest that ALC could represent a new tool in the treatment of severe hepatic encephalopathy.     

Oral fludarabine and cyclophosphamide as front-line chemotherapy in patients with chronic lymphocytic leukemia. The impact of biological parameters in the response duration

We tested the efficacy and safety of oral fludarabine and cyclophosphamide as front-line therapy in chronic lymphocytic leukemia (CLL) and assessed the influence of immunoglobulin variable region heavy chain (IgVH) gene mutation status, interphase cytogenetic abnormalities, and expression of ZAP-70 and CD38 on clinical outcome. Thirty-seven patients with previously untreated CLL received oral fludarabine (30 mg m²) and oral cyclophosphamide (250 mg m²) for three consecutive days every 4 weeks for six cycles. Eighteen patients had unmutated and 15 had mutated IgVH genes. Nine patients had the ‘high risk’ cytogenetic abnormality del(11q22.3) or del(17p13.1). Fifteen patients were ZAP-70-positive and eight patients were CD38-positive. Among the 35 valuable patients, 14 patients (40%) obtained a complete response and 13 (37%) a partial response. The median progression-free survival (PFS) was 23 months and median time to re-treatment (TTR) was 38 months. A significantly lower overall response rate (43% vs. 85%, p = 0.011), a shorter PFS (22 vs. 27 months, p = 0.015), and a shorter TTR (22 vs. 40 months, p = 0.031) were noticed in the ‘high risk’ cytogenetic abnormalities group; TTR was also shorter in IgVH-unmutated than in IgVH-mutated patients (26 vs. 41 months, p = 0.035). Hematologic toxicity included grade IV neutropenia (ten patients) and grade III/IV anemia (three patients). Gastrointestinal toxicity was mild and no patient required hospitalization. The oral combination of fludarabine and cyclophosphamide is an effective, safe, and well-tolerated regimen that, if confirmed with larger series, will be appropriate especially in patients with low risk biological parameters.     

Reassessment of the prognostic factors of international prognostic index (IPI) in the patients with diffuse large B-cell lymphoma in an era of R-CHOP in Chinese population

We performed this study to reassess the prognostic factors of diffuse large B-cell lymphoma (DLBCL) in the era of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Chinese population. One hundred and twenty-five consecutive patients with DLBCL were enrolled in this study from February 2000 to September 2006. They had received six courses of R-CHOP regimen consisting of rituximab 375 mg/m², intravenously, D1; cyclophosphamide 750 mg/m², bolus infusion, D2; doxorubicin 50 mg/m², bolus infusion, D2; vincristine 1.4 mg/m², bolus infusion, D2; and prednisone 60 mg, orally, D2-6. All the patients were evaluated and followed-up after the treatment. Eighty-six out of 125 enrolled patients (68.8%) achieved complete response (CR), 16 patients (12.8%) achieved partial response (PR), 11 patients (12.8%) achieved stable disease, and 12 patients (9.6%) experienced progressive disease (PD). In univariate analysis, IPI factors, except for age, was correlated with the treatment outcome of complete remission; however, only early clinical stages and absence of bulky disease was statistically significantly associated with the better CR rate. Lactate dehydrogenase (LDH), extranodal diseases, bulky disease, and obtaining CR after completion of four courses of treatment was correlated with TTF (P = 0.038, 0.044, 0.034, and 0.000, respectively); performance status, LDH level, number of extranodal diseases, and obtaining CR after completion four courses of treatment significantly influenced OS (P = 0.027, 0.000, 0.019, and 0.000, respectively); and presence of bulky disease and obtaining CR at the end of fourth cycle of treatment were significantly correlated with DFS in multivariate analysis (P = 0.006 and 0.001, respectively) in Cox regression. IPI is still important in predicting the prognosis in the R-CHOP era in DLBCL; however, obtaining CR after four cycles of R-CHOP and presence of bulky disease should be considered together. Shen Yang and Yao Yu contribute equally to this work.     

Local recurrence after curative resection in patients with colon and rectal cancers

Background and aims  There are a range of rates and a number of prognostic factors associated with the local recurrence of colorectal cancer after curative resection. The aim of this study was to identify the potential prognostic factors of local recurrence in patients with colon and rectal cancers. Materials and methods  A retrospective review of 1,838 patients who underwent curative resection of non-metastatic colorectal cancer was conducted. The patients were treated between 1994 and 2004, and had a minimum follow-up of 3 years. Results  There were 994 patients with colon cancer and 844 patients with rectal cancer. The median duration of follow-up was 60.9 ± 24.5 months. With respect to colon cancer, the local recurrence rate was 6.1% (61 patients). With respect to rectal cancer, 95 patients had a local recurrence (11.3%), the rate of which was statistically greater than the local recurrence rate for colon cancer (p < 0.001). The overall recurrence rate was 16.4% (301 patients), and the local recurrence rate, with or without systemic metastases, was 8.5% (156 patients). Local recurrences occurred within 2 and 3 years in 59.9% and 82.4% of the patients, respectively. In patients with colon and rectal cancer, the pathologic T stage (p = 0.044 and p = 0.034, respectively), pathologic N stage (p = 0.001 and p < 0.001, respectively), and lymphovascular invasion (p = 0.013 and p = 0.004, respectively) were adverse risk factors for local recurrence. The level of the anastomosis from the anal verge was an additional prognostic factor (p = 0.007) in patients with rectal cancer. Conclusion  Compulsive follow-up care of patients with colon and rectal cancers is needed for 3 years after curative resection, especially in patients who have adverse risk factors for local recurrence.