Man-Hsin Hung

Incidence and risk of mood disorders in patients with breast cancers in Taiwan: a nationwide population-based study

The objective of this study is to assess the incidence and risk of mood disorders, including major depression, anxiety, and bipolar disorders, in Taiwanese patients after the diagnosis of breast cancer compared with a matched cohort.

Effect of Age and Biological Subtype on the Risk and Timing of Brain Metastasis in Breast Cancer Patients

Background Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. Patients and Methods We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Results Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (Pu200a=u200a0.507). Among patients aged 36–59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Conclusions Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

Comparison of prognostic models for patients with diffuse large B-cell lymphoma in the rituximab era

Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1u2009×u2009109/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13xa0%, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies.

Secondary Primary Malignancy Risk among Patients with Esophageal Cancer in Taiwan: A Nationwide Population-Based Study

Background To evaluate the risk and sites of metachronous secondary primary malignancies (SPMs) among patients with esophageal cancer. Methods Newly diagnosed esophageal cancer patients between 1997 and 2011 were recruited. To avoid surveillance bias, SPMs that developed within one year were excluded. Standardized incidence ratios (SIRs) of metachronous SPMs in these patients were calculated by comparing to the cancer incidence in the general population. Risk factors for SPM development, included age, sex, comorbidities and cancer-related treatments, were estimated by Cox proportional hazards models. Results During the 15-year study period, 870 SPMs developed among 18,026 esophageal cancer patients, with a follow-up of 27,056 person-years. The SIR for all cancers was 3.53. The SIR of follow-up period ≥ 10 years was 3.56; 5–10 years, 3.14; and 1–5 years, 3.06. The cancer SIRs of head and neck (15.83), stomach (3.30), lung and mediastinum (2.10), kidney (2.24) and leukemia (2.72), were significantly increased. Multivariate analysis showed that age ≥ 60 years (hazard ratio [HR] 0.74), being male (HR 1.46) and liver cirrhosis (HR 1.46) were independent factors. According to the treatments, major surgery (HR 1.24) increased the risk, but chemotherapy was nearly significant. Conclusions Patients with esophageal cancer were at increased risk of developing metachronous SPMs. The SIR remained high in follow-up > 10 years, so that close monitoring may be needed for early detection of SPM among these esophageal cancer patients.

The Risk of Cancer in Patients with Benign Anal Lesions: A Nationwide Population-based Study

OBJECTIVEnTo evaluate the risk of cancer among patients diagnosed with hemorrhoids and benign anal inflammatory lesions.nnnMETHODSnA population-based, retrospective cohort study was conducted that included patients diagnosed with hemorrhoids or benign inflammatory anal lesions (eg, anal fissure, fistula, and perianal abscesses) that were registered in the National Health Insurance Research Database in Taiwan between January 1, 2000 and December 31, 2010. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence of these patients to the general population.nnnRESULTSnDuring a median observation period of 6.23 years, 3080 cancers developed among 70,513 hemorrhoid patients, with a follow-up period of 438,425.6 person-years, entailing the SIR of 1.52 (95% confidence interval [CI], 1.47-1.58). Increased cancer risk (SIR 1.16; 95% CI, 1.11-1.21) was still noted even after excluding the first year of observation. Significant long-term risk for colorectal cancer (SIR 1.50; 95% CI, 1.35-1.66) and prostate cancer (SIR 1.40; 95% CI, 1.17-1.66) was observed after corrections were made for multiple comparisons. In contrast, there was no remarkable increase in cancer risk for patients with inflammatory anal lesions when cancers detected within the first year of diagnosis were excluded.nnnCONCLUSIONnThe presence of hemorrhoids is associated significantly with a long-term risk of developing colorectal cancer or prostate cancer. In contrast, benign inflammatory anal lesions do not appear to increase the risk of malignancy.

The Risk of Cancer in Patients with Generalized Anxiety Disorder: A Nationwide Population-Based Study

Objective To evaluate the risk of cancer among patients with generalized anxiety disorder (GAD) in a nationwide population-based dataset. Methods We recruited newly-diagnosed GAD patients aged 20 years or older without antecedent cancer from the Taiwan National Health Insurance Research database between 2000–2010. Standardized incidence ratios (SIRs) of cancers were calculated in GAD patients, and the subgroup of GAD patients diagnosed by psychiatric specialists. Results A total of 559 cancers developed among 19,793 GAD patients with a follow-up of 89,485 person-years (median follow-up of 4.34 years), leading to a significantly increased SIR of 1.14 [95% confidence interval (CI) 1.05–1.24]. Male GAD patients had a significantly increased SIR overall (1.30, 95% CI 1.15–1.46) and for lung and prostate cancer (1.77, 95% CI 1.33–2.30 and 2.17, 95% CI 1.56–2.93, respectively). Patients over 80 years of age also had a significantly increased SIR (1.56, 95% CI 1.25–1.92), especially in males. However, psychiatrist-diagnosed GAD patients did not show increased cancer risk relative to the general population, perhaps due to having fewer physical comorbidities than non-psychiatrist-diagnosed GAD patients. Conclusion This study found that overall cancer risk is elevated among patients with GAD. The risk of lung and prostate cancer also increased in male patients with GAD. This increased cancer risk may be due to physical comorbidities and surveillance bias. Further prospective study is necessary to confirm these findings.

The association between prostate cancer and mood disorders: a nationwide population-based study in Taiwan

BACKGROUNDnThis study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients.nnnMETHODSnFrom 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status.nnnRESULTSnFinal analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30-1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25-2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders.nnnCONCLUSIONnWe observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.

Patients with diffuse large B cell lymphoma in partial response or stable disease after first-line R-CHOP: the prognostic value of the absolute lymphocyte count and impact of autologous stem cell transplantation

Certain portions of patients with diffuse large B cell lymphoma (DLBCL) do not achieve a complete remission after first-line rituximab combining chemotherapy. This retrospective study aimed to characterize the outcome of patients with DLBCL that achieved partial remission or had stable disease after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). The effects of subsequent treatments and factors associated with event-free survival (EFS) after second-line treatments were analyzed. A total of 103 patients were enrolled and 81 (76.8xa0%) patients received intensive chemotherapy, whereas the others (23.2xa0%) received either palliative chemotherapy or supportive care post first-line treatment. Patients receiving intensive chemotherapy had significantly higher EFS (median 7.9xa0months) than the others; 28 (34.6xa0%) patients in this group received autologous stem cell transplantation (ASCT), which may have further improved the EFS. An International Prognostic Index (IPI) >2 and absolute lymphocyte count (ALC) at diagnosis <1,000/UL were significant prognostic factors associated with worse EFS. The survival advantage of ASCT remained significant after adjustment for these factors. The results suggest intensive chemotherapy plus ASCT may provide modest disease control in patients with DLBCL who achieve PR or SD to first-line R-CHOP, particularly in those with a higher IPI score and/or low ALC at diagnosis.

Palbociclib induces activation of AMPK and inhibits hepatocellular carcinoma in a CDK4/6 independent manner

Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor‐positive breast cancer patients. The effects of palbociclib as a treatment for other malignancies, including hepatocellular carcinoma (HCC), are of great clinical interest and are under active investigation. Here, we report the effects and a novel mechanism of action of palbociclib in HCC. We found that palbociclib induced both autophagy and apoptosis in HCC cells through a mechanism involving 5′ AMP‐activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5) inhibition. Blockade of AMPK signals or ectopic expression of PP5 counteracted the effect of palbociclib, confirming the involvement of the PP5/AMPK axis in palbociclib‐mediated HCC cell death. However, CDK4/6 inhibition by lentivirus‐mediated shRNA expression did not reproduce the effect of palbociclib‐treated cells, suggesting that the anti‐HCC effect of palbociclib is independent of CDK4/6. Moreover, two other CDK4/6 inhibitors (ribociclib and abemaciclib) had minimal effects on HCC cell viability and the PP5/AMPK axis. Palbociclib also demonstrated significant tumor‐suppressive activity in a HCC xenograft model, which was associated with upregulation of pAMPK and PP5 inhibition. Finally, we analyzed 153 HCC clinical samples and found that PP5 expression was highly tumor specific and was associated with poor clinical features. Taken together, we conclude that palbociclib exerted antitumor activity against HCC through the PP5/AMPK axis independent of CDK4/6. Our findings provide a novel mechanistic basis for palbociclib and reveal the therapeutic potential of targeting PP5/AMPK signaling with a PP5 inhibitor for the treatment of hepatocellular carcinoma.

Cancer risk among patients with coal workers' pneumoconiosis in Taiwan: a nationwide population-based study.

This study is aimed to evaluate the cancer risk among patients with coal workers pneumoconiosis (CWP) using a nationwide population‐based dataset. Patients without previous cancer who had been diagnosed with CWP and followed‐up for more than 1 year between 1997 and 2006 were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of cancers in CWP patients were calculated and compared to the cancer incidence in the general population. Risk factors for cancer development were also analyzed. After a median follow‐up of 9.68 years, 954 cancers developed among 8,051 recruited CWP patients, with a follow‐up of 69,398 person‐years. The SIR for all cancers was 1.12 [95% confidence interval (CI) 1.04–1.18]. Males older than 80 years had a SIR of 1.27 (95% CI: 1.06–1.51). The SIRs of esophageal (1.76, 95% CI: 1.24–2.44), gastric (1.42, 95% CI: 1.13–1.76), liver and biliary tract (1.18, 95% CI: 1.01–1.37) and lung and mediastinal (1.45, 95% CI: 1.26–1.66) cancers were significantly higher in the CWP group than in the general population. Multivariate analysis showed that ageu2009≥u200960 years [hazard ratio (HR) 1.70, 95% CI: 1.41–2.05), male gender (HRu2009=u20091.79, 95% CI: 1.44–2.23) and liver cirrhosis (HRu2009=u20093.99, 95% CI: 2.89–5.51) were significant predictors of cancer development in patients with CWP. We concluded that patients with CWP, especially elderly males, were at increased risk of cancer. Age, male gender and liver cirrhosis were independent risk factors for cancer development.