Omission of Chemotherapy in Early Stage Nasopharyngeal Carcinoma Treated with IMRT: A Paired Cohort Study

The objective of this study was to evaluate the necessity of concurrent chemotherapy in T1-2N1 nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT).The retrospective analysis was conducted using the paired comparison method. We matched cases to controls using the greedy matching algorithm with 1:1 control to case ratio. Controls were matched to cases by factors including age, gender, T stage, and duration of RT. The control group included patients received IMRT alone. In another group, concurrent chemotherapy (DDP 40 mg/m²/w) was administrated to each paired patient.From Jan 2009 to Dec 2011, a total of 86 well-balanced T1-2N1 (2002 UICC staging system) NPC patients were retrospectively analyzed. Half of them (43 patients) received radical IMRT alone and another 43 received concurrent chemotherapy with IMRT (CCRT). Median follow-up is 37.4 months (4.8–66.2 months). All patients received a radiation dose of 66Gy/30Fx. In the CCRT group, all patients received a cumulative dose of ≥200 mg/m². The differences of 3-year overall survival (OS), 3-year progression-free survival (PFS), 3-year relapse-free survival (RFS), and 3-year metastasis-free survival (MFS) between 2 groups were not significant (P > 0.05). The most frequently increased toxicities related to chemotherapy were mild to moderate leukopenia (P = 0.003) and mild anemia (P = 0.008).Omission of weekly cisplatin chemotherapy resulted in comparable survival outcomes to CCRT in IMRT populations. More data from future randomized trials are warranted to further confirm it.     

Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide,prospective, inception cohort study

Objective: To compare disease severity classification systems for six-month outcome prediction in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Patients with newly diagnosed AAV from 53 tertiary institutions were enrolled. Six-month remission, overall survival, and end-stage renal disease (ESRD)-free survival were evaluated.

Results: According to the European Vasculitis Study Group (EUVAS)-defined disease severity, the 321 enrolled patients were classified as follows: 14, localized; 71, early systemic; 170, generalized; and 66, severe disease. According to the rapidly progressive glomerulonephritis (RPGN) clinical grading system, the patients were divided as follows: 60, grade I; 178, grade II; 66, grade III; and 12, grade IV. According to the Five-Factor Score (FFS) 2009, 103, 109, and 109 patients had ≤1, 2, and ≥3 points, respectively. No significant difference in remission rates was found in any severity classification. The overall and ESRD-free survival rates significantly differed between grades I/II, III, and IV, regardless of renal involvement. Severe disease was a good predictor of six-month overall and ESRD-free survival. The FFS 2009 was useful to predict six-month ESRD-free survival but not overall survival.

Conclusions: The RPGN grading system was more useful to predict six-month overall and ESRD-free survival than the EUVAS-defined severity or FFS 2009.     

Pulmonary Fibrosis in Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis: A Series of 49 Patients and Review of the Literature

Pulmonary fibrosis (PF) is an uncommon manifestation observed in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA). While patients with PF associated with AAV seem to have a worse prognosis, these patients have been described only in case reports or small retrospective case series. In this retrospective multicenter study, we report the main features and long-term outcomes of patients with PF associated with AAV, fulfilling the American College of Rheumatology criteria and/or Chapel Hill definitions. Forty-nine patients (30 men [61%]; median age at diagnosis of AAV, 68 [interquartile range, 58–73] years) with PF associated with AAV were identified. Forty (81.6%) patients had MPA and 9 (18.4%) had granulomatosis with polyangiitis. The diagnosis of PF preceded the onset of vasculitis in 22 (45%) patients. Usual interstitial pneumonia was the main radiologic pattern (n = 18, 43%). ANCA were mostly of antimyeloperoxidase specificity (88%). All patients were treated with glucocorticoids as induction therapy, combined with cyclophosphamide (CYC) (n = 36, 73.5%) or rituximab (RTX) (n = 1, 2%). Factors associated with mortality included occurrence of chronic respiratory insufficiency (hazard ratio [HR], 7.44; 95% confidence interval [CI], 1.6–34.5; p = 0.003), induction therapy with glucocorticoids alone (HR, 2.94; CI, 1.05–8.33; p = 0.04), and initial weigh loss (HR, 2.83; CI, 1.05–7.65; p = 0.041). The 3-year survival rate in patients treated with glucocorticoids alone or combined with an immunosuppressant (CYC or RTX) as induction therapy was 64% (95% CI, 41–99) and 94% (95% CI, 86–100), respectively (p = 0.03). After a median follow-up of 48 months [interquartile range, 14–88 mo], 18 (37%) patients died, including 11 related to respiratory insufficiency. PF is a rare manifestation of AAV with a very poor prognosis. Induction therapy with CYC might improve the outcome.     

Predictors and outcome of renal flares after successful cyclophosphamide treatment for diffuse proliferative lupus glomerulonephritis

OBJECTIVE: To study the incidence, predictors, and outcome of renal flares after successful cyclophosphamide (CYC) treatment for diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE). METHODS: Between 1988 and 2001, patients with biopsy-proven SLE DPGN who were treated initially with prednisone and CYC were studied. Those who responded to CYC were followed up for the occurrence of renal flares. The cumulative risk, predictors, and outcome of renal flares were evaluated. RESULTS: We studied 189 patients (167 women; and 22 men) with SLE DPGN. All were initially treated with prednisone and CYC (49% orally; 51% by intravenous pulse). At the last dose of CYC, 103 patients (55%) and 52 patients (28%) had achieved complete and partial renal responses, respectively. Azathioprine (AZA) was given as maintenance therapy in 117 patients (75%). After a mean followup of 96.5 months, 59 patients (38%) experienced renal flares (42% nephritic; 58% proteinuric). The median time to relapse was 32 months. The cumulative risk of renal flare was 28% at 36 months and 44% at 60 months. Independent predictors of nephritic flares were persistently low C3 levels after CYC treatment and absence of AZA maintenance therapy. At the last clinic visit, 16 patients (10.3%) had developed doubling of the serum creatinine level (cumulative risk of creatinine doubling 7.4% at 5 years after renal biopsy and 14.3% at 10 years). Ten patients (6.5%) developed end-stage renal disease (ESRD). Renal survival rates at 5 and 10 years were 94.9% and 87.5%, respectively. Increasing histologic chronicity scores, failure to achieve complete response, persistent hypertension after CYC treatment, and nephritic renal flares were unfavorable factors for doubling of the serum creatinine level and for ESRD by univariate analysis. The occurrence of nephritic flares was the only predictor of creatinine doubling by Cox regression analysis. CONCLUSION: In patients with SLE DPGN, renal flares are common despite initial responses to CYC. Nephritic renal flares are associated with a decline in renal function. Maintenance therapy with AZA reduces, but does not completely prevent, renal flares. More effective maintenance treatment for SLE DPGN after an initial response to CYC should be evaluated.     

Stereotactic Body Radiation Therapy for Prostate Cancer Patients with Old Age or Medical Comorbidity: A 5-year Follow-Up of an Investigational Study

We evaluated 5-year follow-up of stereotactic body radiation therapy (SBRT) with Cyberknife for prostate cancer patients.Forty-five men with prostate adenocarcinoma who received SBRT using Cyberknife from May 2006 to November 2012 were enrolled in this study. They were prostate cancer patients with old age and medical comorbidities who received a total of 36 Gy to the prostate in 5 fractions with either everyday or every other day schedule. Prostate-specific antigen (PSA) levels at initial diagnosis and after radiation were traced. Primary endpoints were biochemical relapse-free survival (bRFS), progression-free survival (PFS), and overall survival (OS). The definition of biochemical relapse was a PSA level of nadir + 2 ng/mL. Progression was defined as biochemically or clinically detected disease and the start of salvage therapy.After median follow-up of 63 months, the 5-year bRFS for all patients was estimated at 89.7%. The 5-year PFS was estimated at 71%. Four cases of biochemical relapse were observed, including two patients who experienced locoregional failure and one patient who had distant metastasis with biochemical relapse. The 5-year OS was estimated at 94.3%. There were five deaths, all of which were unrelated to prostate cancer. There was no grade 3 or higher acute complication. Grade 3 or higher late urinary toxicity was reported in 2 (4.4%) of 45 patients.The 5-year survival and toxicity outcome of SBRT using Cyberknife on prostate cancer patients with old age or comorbidities were favorable and safe in an investigational study.     

Analysis of clinical characteristics and prognosis of patients with peripheral T-cell lymphoma

Background:This study aimed to explore the clinical characteristics, therapeutic efficacy and prognostic factors of peripheral T-cell lymphoma (PTCL).Methods:The clinical data of 119 PTCL patients who were admitted to the Xinjiang Medical University Affiliated Tumor Hospital from January 2010 to December 2017 were retrospectively analyzed, including the clinical characteristics, therapeutic efficacy, prognosis-related factors and treatments. Among the patients, 98 patients received antharcyclines-based therapeutic protocols, including Cyclophosphamide, Pirarubicin, Vincristine, Prednisone (CHOP) protocol and Cyclophosphamide, Pirarubicin, Vincristine, Prednisone, Etoposide (CHOPE) protocol, with median follow-up time of 32.5 months (2–166 months). The patients’ clinical characteristics were analyzed, and COX ratio risk regression model was adopted to analyze the prognostic factors related with the survival rate of PTCL patients.Results:The 5-year overall survival (OS) rate was 46.4% and progression-free survival (PFS) rate was 42.7% in the 98 patients, and there were insignificant differences between patients with CHOP protocol and those with CHOPE protocol in the 5-year OS and PFS rates (OS: P = 0.197, PFS: P = 0.663). The univariate analysis results showed that different pathological types, Ann Arbor stage, Eastern Cooperative Oncology Group (ECOG) score ≥ 2, the number of extranodal lymphomas involved, Lactic dehydrogenase (LDH) level, presence/absence of bone marrow involved, international prognostic index (IPI) score, β₂ microglobulin (β₂-MG) level and hemoglobin (Hb) level were poor prognosis factors influencing patients’ OS and PFS rates (P all < .05). Multivariate analysis demonstrated that different pathological types, Ann Arbor stage, presence/absence of bone marrow involved and Hb level were independent prognostic indicators influencing patients’ OS and PFS rates (P all < .05).Conclusion:PTCL is poor in therapeutic efficacy and prognosis, and different pathological types, Ann Arbor stage, presence/absence of bone marrow involved and Hb level are related with the prognosis of PTCL patients. Anemia occurring before the treatment is an important predictive indicator influencing the prognosis of PTCL patients and patients who experience anemia will be poor in prognosis.     

Efficacy and safety of tacrolimus monotherapy versus cyclophosphamide–corticosteroid combination therapy for idiopathic membranous nephropathy: A meta-analysis

ObjectiveThe objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus cyclophosphamide (CTX)-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients.MethodsDatabases including the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from inception to October 20, 2020. Eligible studies comparing TAC monotherapy and CTX-corticosteroid combination therapy in IMN patients were included. Data were analyzed using Review Manager Version 5.3.ResultsNine studies were included in the meta-analysis. One randomized controlled trial and eight cohort studies involving 442 patients were identified. Compared with CTX-corticosteroid combination therapy for IMN, TAC monotherapy had higher complete remission (CR) at month 6 (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.35–3.50, P < .01). The 2 therapeutic regimens had similar partial remission (OR 0.69, 95% CI 0.45–1.04, P = .08), total remission (OR 1.38, 95% CI 0.85–2.23, P = 0.19) at month 6, and similar CR (OR 1.64, 95% CI 0.84–3.19, P = .15), partial remission (OR 0.71, 95% CI 0.37–1.38, P = 0.31), and total remission (OR 1.29, 95% CI 0.55–3.01, P = .56) after 1 year. The relapse rate of the TAC group was higher than that of the CTX group, but the difference was not statistically significant (OR 1.85, 95% CI 0.75–4.53, P = .18). There was no difference between the 2 therapeutic regimens concerning glucose intolerance (OR 1.15, 95% CI 0.61–2.14, P = .67), acute renal failure (OR 1.14, 95% CI 0.39–3.33, P = .81), or tremors (OR 4.39, 95% CI 0.75–25.67, P = .10). Incidences of gastrointestinal symptoms (OR 0.29, 95% CI 0.10–0.79, P = .02), infection (OR 0.18, 95% CI 0.08–0.39, P < 0.01), leukopenia (OR 0.14, 95% CI 0.04–0.51, P < .01), and abnormal aminotransferase (OR 0.31, 95% CI 0.13–0.77, P = .01) in the TAC group were all lower than those in the CTX group. Subgroup analysis showed that there was no significant difference between the TAC group and the CTX combined with corticosteroid 0.8 to 1 mg/kg/day group concerning CR at month 6 (P > .05). There was no significant difference between the TAC group and the CTX combined with corticosteroid 0.5 mg/kg/day group concerning abnormal aminotransferase (P > .05).ConclusionTAC monotherapy is comparable to CTX-corticosteroid combination therapy for renal remission in IMN patients. TAC monotherapy had a higher CR in the early stage and had fewer drug-related adverse effects. The relapse rate of TAC monotherapy was higher than that of CTX-corticosteroid combination therapy, but the difference was not significant.     

Survival Prediction Model Using Clinico-Pathologic Characteristics for Nonsmall Cell Lung Cancer Patients After Curative Resection

The current TNM staging system did not provide disease relapse information. The aim of study was try to establish a predictive survival model for disease and overall survival in nonsmall cell lung cancer patients who presented as resectable disease and to develop a reference for follow-up imaging tool selection.From January 2005 to December 2011, 442 patients who initially presented as resectable disease (stages I–IIIa) and received anatomic resection and mediastinal lymph node dissection were included in the study.Medical charts were thoroughly reviewed and clinico-pathologic factors were collected and analyzed.Visceral pleural invasion, tumor size >5 cm, and postoperative adjuvant therapy were identified as risk factors for poorer disease-free survival. The 5-year disease-free survival from score 0 to 3 was 68.7%, 46.6%, 31.9%, and 26.1%, respectively. The disease relapse percentage for scores 0 to 3 were 26.49%, 50.61%, 65.05%, and 73.81%, respectively. For analysis of overall survival, age >60 years, tumor size >3 cm, and total metastatic lymph node ratio >0.05 were correlated to worse overall survival. Because greater age may be correlated with poor general condition, we re-scored risk factors that correlated to disease severity that ranging from 0 to 2. The 5-year overall survival range from score 0 to 2 was 56.3%, 43.1%, and 13.1%, respectively.Poor prognostic factors correlated to disease-free survival were tumor size >5 cm, visceral pleural invasion, and patients needing to receive postoperative adjuvant therapy. Disease-free survival of resectable nonsmall cell lung cancer patients and disease relapse can be stratified by these 3 factors. Chest tomography may be recommended for patients with 1 or more poor disease-free survival risk factors.     

Reduced Red Blood Cell Count Predicts Poor Survival After Surgery in Patients With Primary Liver Cancer

Currently, the optimal therapy of primary liver cancer (PLC) remains to be hepatic resection. For better management of the patients, we evaluated the prognostic predicting value of red blood cell (RBC) count, a routine laboratory parameter, on the long-term survival of patients who underwent surgical treatment.Clinical and laboratory data of 758 patients, who underwent surgical hepatic resection, were retrospectively studied by χ² tests and logistic regression. All patients were enrolled at Henan Cancer Hospital, Zhengzhou, China, from February 2009 to July 2013, and none of them received any other treatments before surgery. Kaplan–Meier survival analysis and Cox proportional hazard models were used to examine the influence of RBC counts on patients’ survival.The Cox univariate and multivariate analyses showed that preoperative RBC count was an independent risk factor of poor prognosis after surgical treatment. The Kaplan–Meier curves showed that the overall survival (OS) of patients without reduced preoperative RBC counts was significantly better than those patients with reduced preoperative RBC counts (P < 0.001). Concordantly, compared with the patients with either reduced preoperative and/or postoperative RBC counts, patients without reduced RBC counts preferred to be low Child–Pugh grades (P = 0.0065), which implies a better hepatic function. In addition, low RBC count was found to be significantly associated with patients of female (P = 0.003), younger age (P =  < 0.001), and with higher AST/ALT ratio (P = 0.005).This study revealed that patients with preoperative RBC counts lower than normal had worse OS rates than those without reduced preoperative RBC counts, perhaps due to the significant correlation of reduced preoperative RBC count to patients’ worse Child–Pugh grade that reflect the loss of liver functions.     

Long-term outcomes after different treatments for gastric cancer with synchronous liver metastasis: A PRISMA systematic review and network meta-analysis

Background:The treatment of gastric cancer (GC) with synchronous liver metastasis is still controversial. This systematic review and network meta-analysis was designed to evaluate the long-term outcomes after different treatments of GC with synchronous liver metastasis.Methods:Several electronic databases were searched to identify eligible studies updated on May 1, 2021. Studies assessing the overall survival (OS) after different treatments (including chemotherapy, interventional therapy, surgical therapy alone and adjunctive therapy after surgery) of GC with synchronous liver metastasis were included. Odds ratios with 95% confidence interval (CI) were calculated for survival variables.Results:A total of 15 studies including 4312 patients were included in this network meta-analysis. Adjunctive therapy after surgery performed better than surgery therapy alone (hazard ratio [HR] = 1.23, 95% credible interval [CrI]: 0.69–2.17), chemotherapy (HR = 1.18, 95%CrI: 0.71–1.95), and interventional therapy in terms of 1-year OS (HR = 2.03, 95%CrI: 1.22–3.37). In terms of 3-OS, adjunctive therapy after surgery showed better efficacy than surgery therapy alone (HR = 1.48, 95%CrI: 0.40–5.47), chemotherapy (HR = 1.27, 95%CrI: 0.37–4.35), and interventional therapy (HR = 3.16, 95%CrI: 0.73–13.63). For 5-OS, adjunctive therapy after surgery was superior to surgery therapy alone (HR = 1.74, 95%CrI: 0.08–37.76), chemotherapy (HR = 1.44, 95%CrI: 0.66–3.14), and interventional therapy (HR = 1.46, 95%CrI: 0.06–34.36). There were no statistical inconsistency and small-study effect existed in our network meta-analysis for 1-year, 3-year, or 5-year OS. Cluster ranking analysis performed with surface under the cumulative ranking showed adjuvant therapies after surgery (99.9, 96.7, 90.2) ranking higher than surgery therapy alone, chemotherapy, and interventional therapy for 1-year, 3-year, 5-year OS.Conclusion:The OS of adjuvant therapy after surgery was better than that of surgery therapy alone, chemotherapy, and interventional therapy. Adjuvant therapy after surgery is the most recommended therapy for people with GC with synchronous liver metastasis.     

Longterm followup of childhood lupus nephritis

OBJECTIVE: To determine the longterm outcome in children with onset of lupus nephritis before 18 years of age. METHODS: Sixty-seven patients with onset of lupus nephritis prior to age 18 were identified. The mean followup time was 11 years (range 5-19). The mean age at diagnosis was 13.2 years (range 4-17). The male:female ratio was 1:3.8. Renal biopsies were classified using the WHO classification. Fifteen patients had Class II, 8 patients Class III, 32 patients Class IV, and 11 patients Class V and one patient refused biopsy. The cohort consists of the 66 patients who had a renal biopsy. Five patients received cyclophosphamide (CYC) and 17 received azathioprine (AZA) as part of the initial treatment of Class IV nephritis. Eight additional patients received CYC because of a flare of disease while receiving AZA, and 8 other patients received AZA because of a flare of disease while taking prednisone therapy. RESULTS: Four patients died; 6 developed endstage renal disease (ESRD); all but one of the patients who died and/or had ESRD had WHO Class IV [diffuse proliferative glomerulonephritis (DPGN)]; only 2 Caucasians developed ESRD, although 16 out of 36 Caucasians had DPGN; serum creatinine at followup was normal in 84% of the survivors; presently 70% of the patients take less than 7.5 mg prednisone/day and 62% do not take cytotoxic drugs. No patient is currently treated with CYC. All 8 patients with Class III nephritis were taking medication at last followup. CONCLUSION: The longterm outcome in this group of children with lupus nephritis, in whom AZA was the most commonly used immunosuppressive agent, was excellent, with 94% patient survival at a mean followup of 11 years. Our results suggest that non-Caucasian patients with pediatric onset lupus nephritis may be at increased risk for renal failure compared to Caucasians.     

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80–0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80–0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08–1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91–1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82–1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63–1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.     

Long-term efficacy and safety of levonorgestrel-releasing intrauterine system as a maintenance treatment for endometriosis

This study evaluated the efficacy and feasibility of long-term use of levonorgestrel releasing intrauterine system (LNG-IUS) in endometriosis patients after using LNG-IUS for >5 years as their postoperative maintenance therapy.Data were obtained retrospectively from patients who maintained medical therapy for >5 years after surgical treatment of endometriosis from January 2008 to April 2015. Patients were divided into study group and control group according to the type of medication; the study group consisted of patients who received LNG-IUS as maintenance therapy, and patients in the control group received combined oral contraceptives (ethinyl estradiol 20 μg and drospirenone 3 mg) or dienogest 2 mg.A total of 263 patients (94 patients in the study group, 169 in the control group) were included in the study. 91.5% (86/94) of the patients in the study group maintained the treatment for >5 years, whereas only 21.9% (37/169) of patients in the control group maintained the treatment for >5 years.LNG-IUS significantly decreased the pain score for non-cyclic pelvic/back pain (from 4.0 ± 1.6 to 0.6 ± 1.3, P < .001), dysmenorrhea (from 6.5 ± 1.7 to 6.5 ± 1.7, P < .001), and dyspareunia/dyschezia (from 6.5 ± 1.7 to 1.3 ± 1.4, P = .006) after 1 year, and the effect was persistent for 10 years (P < .01). When compared with control group, the effect on pain reduction was comparable to the oral contraceptives or dienogest, with less systemic side effects such as mood change or nausea.LNG-IUS for >5 years as a postoperative maintenance therapy for endometriosis patients is an effective and feasible treatment that shows significant effect on pain reduction with less systemic side effect compared with other types of treatment. Therefore, LNG-IUS can be recommended as a long-term postoperative therapy for endometriosis patients who do not plan to become pregnant for several years.     

Association of the Charlson Comorbidity Index with Renal Outcome and All-Cause Mortality in Antineutrophil Cytoplasmatic Antibody-Associated Vasculitis

The aim of this study is to determine the effect of comorbidity assessed by the Charlson comorbidity index (CCI) at the time of diagnosis on the outcome of antineutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV).This is a longitudinal observational study of 30 consecutive patients with AAV who were diagnosed and followed from January 1996 to December 2011. The degree of comorbidity at diagnosis and last visit was scored according to the age-adjusted Charlson comorbidity index (CCI (a)). The post hoc analysis of increment in CCI during the study period and its predictive value for patient and renal survival were analyzed.Thirty patients with AAV were included in this study. A higher CCI (a) at diagnosis was positively correlated with higher activity score of AAV (P = 0.016), a CCI (a) >5, and with an increased risk for mortality (odds ratio 12; confidence interval 1.8–79.68, P = 0.014). The mean increment (Δ) of CCI (a) during the study period was 1.26 ± 2.03 (6–5). Correlation was found between lower Δ CCI (a) and chronic kidney disease (P = 0.036) and mortality (P = 0.002).Comorbidity at the time of diagnosis of AAV is associated with reduced patient and renal survival. We suggest including the CCI score in the assessment of patients with AAV at diagnosis and at disease relapse.     

Adjuvant therapy for HER2 positive pT1a-b pN0 breast cancer: A single center cohort study

Deciding if patients with small (≤1 cm), node-negative, human epidermal growth factor receptor 2 (HER2) positive breast cancer should receive adjuvant systemic therapy remains a challenge. No randomized clinical trials have examined the efficacy of trastuzumab in this setting. This prospective observational study aimed to investigate the choice of adjuvant systemic therapy in clinical practice in China.We prospectively collected data from patients with HER-2 positive breast cancer (less than 1 cm and node negative) patients who underwent breast cancer surgery at Shanxi Provincial People''s Hospital Breast Center from January 1, 2017 to December 31, 2019, and retrospectively investigated the association between baseline clinicopathological features and treatment strategy, cardiotoxicity, and disease outcome.Of 168 eligible patients, 102 (60.7%) received adjuvant systemic therapy with trastuzumab (AST+T), 47 (28%) received adjuvant systemic therapy without trastuzumab (AST) and 19 (11.3%) did not receive adjuvant systemic therapy. Multivariate logistic regression analysis demonstrated that age, tumor size and hormone receptor status were significantly associated with treatment choice. Three-year invasive disease-free survival probability was 100%, 97.9% and 89.5% with AST+T, AST, and no therapy, respectively (P < .001).The majority of patients (60.7%) with pT1a-b pN0 HER2 positive breast cancer received adjuvant systemic therapy with trastuzumab, whereas only 11.3% did not receive any adjuvant systemic therapy. Tumor size, age and hormone receptor status influenced treatment choice. The 3-year invasive disease-free survival probability was significantly higher for patients who received adjuvant systemic therapy with trastuzumab compared with those who did not receive adjuvant systemic therapy. Cardiac adverse events were rare.     

Association Between Early Helicobacter pylori Eradication and a Lower Risk of Recurrent Complicated Peptic Ulcers in End-Stage Renal Disease Patients

End-stage renal disease (ESRD) patients exhibit an increased incidence of peptic ulcer disease. Helicobacter pylori plays a central role in the development of peptic ulcers. The effect of early H pylori eradication on the recurrence of complicated peptic ulcer disease in ESRD patients remains unclear. The aim of the present study was to explore whether early H pylori eradication therapy in ESRD patients can reduce the risk of recurrent complicated peptic ulcers.We conducted a population-based cohort study and recruited patients with ESRD who had developed peptic ulcers. We categorized patients into early (time lag ≦120 days after peptic ulcer diagnosis) and late H pylori eradication therapy groups. The Cox proportional hazards model was used. The endpoint was based on hospitalization for complicated recurrent peptic ulcers.The early and late H pylori eradication therapy groups consisted of 2406 and 1356 ESRD patients, respectively, in a time lag of 120 days. After adjusting for possible confounders, the early eradication group exhibited a lower rate of complicated recurrent peptic ulcer disease (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.64–0.91, P = 0.003) in a time lag of ≦120 days, but a similar rate of complicated recurrent peptic ulcer disease in time lags of ≦1 year (HR = 0.97, 95% CI 0.79–1.19, P = 0.758) and 2 years (HR = 1.11, 95% CI 0.86–1.44, P = 0.433) compared with the late eradication group.We recommend administering H pylori eradication within 120 days after peptic ulcer diagnosis to H pylori infected ESRD patients who have developed peptic ulcers.     

KRAS Mutation Status Is Not a Predictor for Tumor Response and Survival in Rectal Cancer Patients Who Received Preoperative Radiotherapy With 5-Fluoropyrimidine Followed by Curative Surgery

We evaluated the tumor response and survival according to the KRAS oncogene status in locally advanced rectal cancer. One hundred patients with locally advanced rectal cancer (cT3-4N0-2M0) received preoperative radiation of 50.4 Gy in 28 fractions with 5-fluorouracil and total mesorectal excision. Tumor DNA from each patient was obtained from pretreatment biopsy tissues. A Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was found in 26 (26%) of the 100 patients. Downstaging (ypT0-2N0M0) rates after preoperative chemoradiotheray were not statistically different between the wild-type and mutant-type KRAS groups (30.8% vs 27.0%, P = 0.715, respectively). After a median follow-up time of 34 months, there was no statistically significant difference in the 3-year relapse-free survival (82.2% vs 82.6%, P = 0.512) and overall survival (94.7% vs 92.3%, P = 0.249) rates between wild-type and mutant-type KRAS groups, respectively. The KRAS mutation status does not influence the tumor response to the radiotherapy and survival in locally advanced rectal cancer patients who received preoperative chemoradiotherapy and curative surgery.     

ANCA vasculitis: time for a change in treatment paradigm? Not yet

The ANCA-associated vasculitides (AAVs) are conventionally treated with a strategy of remission induction followed by maintenance therapy using glucocorticoids combined with CYC during induction and AZA for maintenance. Recently, several randomized controlled trials have been published that question whether these drugs should remain those of choice. B-cell depletion using rituximab is at least as effective as CYC for remission induction in newly presenting patients, but long-term efficacy, safety and cost-effectiveness data are awaited, and thus rituximab should be reserved for patients at high risk of infertility. Rituximab seems to be effective at inducing remission in relapsing patients. Whether routine pre-emptive treatment with rituximab for remission maintenance is a better approach than waiting for relapse is unknown. MTX and LEF have similar efficacy to AZA, but are not significantly safer; while MMF is less effective. Thus, AZA remains the conventional maintenance drug of choice.     

Combination therapy of tacrolimus,high doses of glucocorticosteroids,and cyclophosphamide against existing historical treatment for patients in severe conditions of interstitial lung diseases complicated with dermatomyositis: A retrospective analysis

The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0–2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m²/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2–3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m²/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).     

Metronomic capecitabine as maintenance treatment after first line induction with XELOX for metastatic colorectal cancer patients

Maintenance treatment after first-line chemotherapy for patients with metastatic colorectal cancer (mCRC) is a priority strategy. However, which medicine is chosen is controversial. This study aimed to determine the efficacy and safety of maintenance treatment with metronomic capecitabine vs observation.In this randomized controlled trial, patients who completed 18 weeks of induction chemotherapy with XELOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy with metronomic chemotherapy or observation until disease progression. The primary endpoint was progression-free survival from randomization; secondary endpoints included overall survival and safety. Analyses were performed by intention to treat.Between January 1st, 2017 and December 31th 2018, 48 patients were enrolled and randomly assigned to receive maintenance treatment with metronomic capecitabine (n = 25) or only observation (n = 23). The median progression-free survival in the metronomic capecitabine group was 5.66 (95% confidence interval [CI] 5.25–6.07) months vs 3.98 (95%CI 3.71–4.24) months in the observation group (hazard ratio 0.11, 95% [CI] 0.04–0.26, P = .000). There was no statistically significant difference in median overall survival: 23.82 (95% CI 22.38–25.25) months in the metronomic capecitabine group vs 21.81 (95% CI 20.23–23.38) months in the observation group (hazard ratio 0.49, 95% CI 0.21–1.11, P = .087). Subgroup analyses were generally consistent with the primary finding. Similar safety profiles were observed in both arms. The most frequent adverse events in metronomic capecitabine group included neutropenia, diarrhea, hand-foot skin reaction, and mucositis.Maintenance therapy with metronomic capecitabine can be considered an alternative option following first-line chemotherapy of XELOX in patients with metastatic colorectal cancer with controlled toxicities.