Risk of fracture in transfusion-naïve thalassemia population: A nationwide population-based retrospective cohort study.

In thalassemia major or transfusion-dependent thalassemia patients, osteoporosis-related bone complications such as fracture events are common. However, no studies have investigated the risk of fracture in transfusion-naïve thalassemia population. Therefore, we conducted a longitudinal nationwide cohort study to determine whether this population has an increased risk of fracture. This nationwide, population-based cohort study analyzed data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending until the end of 2011. We identified cases with transfusion-naïve thalassemia and selected a comparison cohort that was frequency-matched according to age and year of diagnosis of thalassemia at a ratio of one subject with thalassemia to four subjects in the control group. We analyzed the risk of fracture events to occur in transfusion-naïve thalassemia cases by using Cox proportional hazards regression models. Totally, the study recruited 1369 transfusion-naïve thalassemia subjects and 5416 controls. We identified a total of 71 cases with fracture events within the thalassemia group and 204 within the control group. The overall risks for developing fracture events were 1.35-fold higher in transfusion-naïve thalassemia individuals than the comparison cohort after adjusting for age, sex and comorbidities. Most fracture events were observed in male transfusion-naïve thalassemia individuals rather than the normal population. In subgroup analysis, there was a 1.46-fold higher risk to develop upper-limb fracture in the thalassemia group than in the control groups. In conclusion, our long-term, cohort study results showed that there was a higher risk for the development of fractures in transfusion-naïve thalassemia individuals, particularly in male cases.

Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports.

INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients. Hence, many studies have promoted the synergy of RT and anti-programmed cell death protein 1 (PD-1) treatment for antitumor immunity. However, outcome may be improved when more therapies are combined, but risk of side effects can be increased. CASE PRESENTATION: We herein present 3 advanced cancer patients with pulmonary metastasis and who received RT. Later, they underwent anti-PD-1 treatment and unfortunately suffered from anti-PD-1-related pneumonitis over the nonirradiated areas after 4 cycles of treatment. The upregulation of cellular PD-1 expression in these areas was considered and the immune overreaction by anti-PD-1 treatment may cause these severe pulmonary adverse effects. CONCLUSION: Our review of 3 cases warrants careful workup to reduce the risk of side effects by combinative therapy with RT and anti-PD-1 treatment.

Intraperitoneal ziv-aflibercept effectively manages refractory ascites in colorectal cancer patients.

Ascites related to metastatic colorectal cancer (mCRC) reduces patient survival and quality of life, and systemic chemotherapy is largely ineffective for managing ascites. Here, we examined the clinical efficacy of intraperitoneal (IP) ziv-aflibercept for managing refractory ascites in 15 mCRC patients who did not respond to standard chemotherapy. Fifty or 100 mg of ziv-aflibercept in 100 mL of saline solution were infused through a pigtail catheter and retained for 24 h. When the ascites drainage volumes were subsequently monitored, 73.3% of patients showed an objective response (OR) to IP ziv-aflibercept treatment. Patients with low Eastern Cooperative Oncology Group (ECOG) performance status or with serum ascites albumin gradients (SAAG) less than 1.1 g/dL had better responses to treatment, and 4 patients with SAAG less than 1.1 g/dL showed rapid objective responses (rOR). These findings indicate that intraperitoneal ziv-aflibercept therapy may be a highly effective means of treating refractory ascites in mCRC patients, and that SAAG may be predictive of a rapid response to this treatment.

Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70.

BACKGROUND: The aim of this study was to examine the specific chemoregimens selected for adjuvant therapy in the patients with stage III colon cancer. We investigated the trends in chemotherapeutic prescribing patterns and looked for adequate therapeutic setting for these patients. METHODS: 288 patients presenting with stage III colon cancer and undergoing adjuvant therapies after curative surgery for more than 3-month were enrolled between January 2006 and December 2011. Demographic characteristics and therapeutic factors were analyzed, including age, gender, histological grade, tumor sizes, tumor location, pathologic stage, performance status, serum carcinoembryonic antigen, regimens selection, interval from the operation to the start of adjuvant therapy and prolonged adjuvant therapy. Kaplan- Meier methods were utilized for drawing survival curves and Cox model was used to analyze survival, prognostic factors. RESULTS: The analysis showed that the patients aged under 70 received more intensive therapies than those aged over 70 (P<0.001). Later, advanced analysis in therapeutic factors was conducted between the patients aged under 70 and those over 70. In the patients aged under 70, significant differences in 4-year overall survival (OS) were noted between UFUR (oral tegafur-uracil plus leucovorin) groups and FOLFOX (5-FU plus oxaliplatin) [65.6% versus (vs) 89.8%, relative risk (RR) 3.780, 95% confidence interval (CI) 1.263-11.315, P = 0.017]. There were also differences in 4-year OS between these patients with and without oxaliplatin-contained regimens (92.1% vs 83.4%, respectively, RR 0.385, 95% CI 0.157-0.946, P = 0.037). In addition, the patients who received intravenous or combined therapy also had higher 4-year OS than those only received oral regimens (92.1% vs 76.6%, P = 0.077), though the finding did not reach statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less advantage in the old patients when they received intensive therapies or even oxaliplatin-contained regimens. Prolonged cycles of adjuvant therapy resulted in no significant benefit to survival rates regardless of ages. CONCLUSIONS: The adequate individualized therapeutic strategy plays an important role for stage III colon cancer. Our findings suggested that benefit of oxaliplatin-contained therapy is limited to patients aged under 70 and oral fluoropyrimidines may be an effective option for old patients. In addition, prolonged adjuvant setting is suggested to be unbeneficial for managing stage III colon cancer.

Impact of Comorbidity and Age on Determinants Therapeutic Strategies in Advanced Pancreatic Head Cancer Patients With Obstructive Jaundices.

The current retrospective study aimed to investigate the relationship between prognostic factors and overall survival (OS) in patients with advanced pancreatic head cancers who initially presented with obstructive jaundice. Furthermore, the impact of age and comorbidities on therapeutic strategies in such patients was evaluated.A total of 79 advanced pancreatic head cancer patients who were treated at our institution between January 2006 and November 2013 were reviewed. We analyzed OS risk factors including sex, age, laboratory characteristics, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index Scores (CCIS), and therapeutic strategies using Cox proportional hazards regression models.There was no difference in the OS of patients according to the type biliary drainage procedure they underwent. Other related factors, such as better performance status, lower CCIS, and receiving chemotherapy significantly correlated with survival in multivariate analyses. There was a significant survival benefit in systemic chemotherapy compared to best supportive care (BSC) or local radiotherapy. However, no survival benefit was found in elderly patients (age >70 years) undergoing systemic therapy compared to younger patients, except in those elderly patients with CCIS ≤ 1.In advanced pancreatic head cancer patients with obstructive jaundice, systemic therapy and adequate biliary drainage were still the most effective procedures for improving OS in the general population. However, in elderly patients with relatively higher CCIS, BSC with adequate biliary drainage was palliative and no less effective than systemic/local therapies.

Neutrophil/Lymphocyte Ratio, Lymphocyte/Monocyte Ratio, and Absolute Lymphocyte Count/Absolute Monocyte Count Prognostic Score in Diffuse Large B-Cell Lymphoma: Useful Prognostic Tools in the Rituximab Era.

The neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and absolute lymphocyte count/absolute monocyte count prognostic score (ALC/AMC PS) have been described as the most useful prognostic tools for patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed 148 Taiwanese patients with newly diagnosed diffuse large B-cell lymphoma under rituximab (R)-CHOP-like regimens from January 2001 to December 2010 at the Tri-Service General Hospital and investigated the utility of these inexpensive tools in our patients. In a univariate analysis, the NLR, LMR, and ALC/AMC PS had significant prognostic value in our DLBCL patients (NLR: 5-year progression-free survival [PFS], P = 0.001; 5-year overall survival [OS], P = 0.007. LMR: PFS, P = 0.003; OS, P = 0.05. ALC/AMC PS: PFS, P < 0.001; OS, P < 0.001). In a separate multivariate analysis, the ALC/AMC PS appeared to interact less with the other clinical factors but retained statistical significance in the survival analysis (PFS, P = 0.023; OS, P = 0.017). The akaike information criterion (AIC) analysis produced scores of 388.773 in the NLR, 387.625 in the LMR, and 372.574 in the ALC/AMC PS. The results suggested that the ALC/AMC PS appears to be more reliable than the NLR and LMR and may provide additional prognostic information when used in conjunction with the International Prognostic Index.

Interferon-alpha caused reversible parkinsonism.

Interferon has been used to treat chronic viral hepatitis and several malignancies. However, it may cause various neuropsychiatric adverse effects including parkinsonism. We report a rare case of interferon alpha-2a therapy-related parkinsonism in a 67-year-old man with metastatic papillary renal cell carcinoma and our experience of using Tc-99m-TRODAT-1 single photon emission computed tomography (SPECT) as a tool for evaluation of parkinsonism. Physicians should be alert to the possibility of interferon alpha-2a-related parkinsonism.

Discrimination index of microcytic anemia in young soldiers: a single institutional analysis.

BACKGROUND: The common differential diagnosis of microcytic anemia in young Asian men includes iron deficiency anemia (IDA), α-thalassemia (αT) and ß-thalassemia (ßT). In this study, we aimed to distinguish between these diseases in a distinct population of young men using a specific index. PATIENTS AND METHODS: We retrospectively reviewed the laboratory data of young men with microcytic anemia. The clinical, characteristic and laboratory data, including complete blood cell counts, serum ferritin and hemoglobin electrophoresis results, were collected; genomic DNA mutations were also evaluated. Based on these data, ten discrimination indices were used to differentiate thalassemia from IDA. The sensitivity, specificity, positive and negative predictive values, Youden's index and receiver operating characteristic (ROC) curves were also calculated. RESULTS: A total of 877 patients (92 patients with IDA, 332 with αT and 453 with ßT) were enrolled; the Shine and Lal (S&L) formula was the best method with which to discriminate IDA from thalassemia (100% sensitivity, 91% specificity). The new cut-off values were evaluated, and the approaches used in our study cohort, particularly the Green & King (G&K) formula, significantly increased the accuracies of red cell distribution width-containing indices (cut-off value: 58.66; 89.62% sensitivity and 96.2% specificity; AUC: 0.9716). In addition, when applied properly, these indices could differentiate IDA patients from αT patients, especially Huber-Herklotz index (HH). CONCLUSIONS: The sensitivity and specificity differed among ethnic and age groups. We concluded that when using the original cut-off value, the S&L formula was the best discriminating index for differentiating between IDA and thalassemia in young Asian men. However, when using the G&K formula, the newly obtained cut-off value must be applied to increase accuracy based on the results from our cohort.

Diffuse large B-cell lymphoma: sites of extranodal involvement are a stronger prognostic indicator than number of extranodal sites in the rituximab era.

The National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) is an enhanced prognostic tool that has identified some specific extranodal sites as a poor prognostic factor. We retrospectively analyzed 148 Taiwanese patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)-like regimens from January 2001 to December 2010 at the Tri-Service General Hospital. In univarate analysis, ≥ 2 extranodal involved sites had no significant prognostic relevance (p = 0.108), although extranodal involvement of the lung/pleura, liver, lower urinary tract or bone marrow was a statistically significant poor prognostic factor (p < 0.001). In multivariate analysis, specific extranodal sites had a stronger predictive value for poor prognosis (relative risk 3.654, 95% confidence interval 1.514-8.815, p = 0.004) compared with the number of extranodal sites involved. This finding suggests that specific extranodal involved sites have prognostic value in the R era.

Primary neuroendocrine carcinoma of the breast.

PURPOSE: Primary neuroendocrine carcinoma of the breast (NECB) is a rare distinct type of breast carcinoma. There are only some case reports on this topic published in the past. There is still little known on the optimal treatment outcomes, while a wide variety of treatments is proposed by several authors. In this study we searched the literature on NECB in PubMed to clarify its prognosis and possible optimal therapeutic strategies. METHODS: Eighty-six cases of primary NEC, included our case, were collected from PubMed between 1980 and 2013. Initial stage, estrogen receptor (ER)/progesterone receptor (PR)/ human epidermal growth factor receptor 2 (HER-2), surgical procedures, adjuvant treatment and overall survive (OS) were analyzed using the Statistical Package for the Social Sciences ( SPSS, v 16.0 ). RESULTS: All 86 patients enrolled were eligible. Their mean age at diagnosis was 53.9 years (range 25-83) and 1 case was in a male. Overall survival (OS) at 48 months was 83.5%. Patients with enlarged tumor size (10 patients with tumor size >5.0 cm) or advanced stage (stage III 15 patients, stage IV 2 patients) had poor OS (48-month OS: 51.4 vs 97.1% with tumors >5cm vs ≤2cm, respectively and 0.0%, 68.1%, 72.9% and 95.8% in stage IV, III, II and I, respectively). Patients with positive ER, PR or HER-2 had significantly better OS than did those without (ER, p<0.001; PR, p<0.001; HER-2, p=0.082). Besides, all 60 patients with initial primary surgery and without lymph node dissection (LND) showed better OS than those with initial primary surgery without LND, the difference however being not significant (p=0.133). CONCLUSION: Definite diagnosis and clinical stage are prerequisites in the initial approach in NECB. When detected early the disease may have a good prognosis with combined modality treatment such as chemotherapy, surgery, and radiation therapy. An appropriate therapeutic strategy for this group is also important. Our analysis showed that for patients with early localized disease only primary surgery is recommended and LND is optional. In patients with positive steroid receptors postoperative hormonotherapy is suggested.