Biomedical Informatics

Extraosseous uptake of bone seeking agents on a bone scan can result from a variety of causes, which need further verification. We present a 61-year-old woman with breast cancer post surgery and adjuvant chemotherapy who underwent radiotherapy over the left chest. The 99m Tc-MDP bone scan performed one hour after one fraction of external beam irradiation showed increased MDP uptake in the irradiated left hemithorax.

Endometriosis is a common medical condition with rare reports of FDG findings in the scintigraphic literature. We present a 36-year-old premenopausal woman with a left ovarian endometrioma that presents a photopenic defect on the FDG-PET scan. The case demonstrates the value of FDG-PET scan in differentiating benign from malignancy in surveying ovarian lesions. The literature associated with endometriomas and FDG-PET scan, and the factors that may contribute to FDG-PET finding of endometriomas are discussed.

Sequential palliative chemotherapy for metastatic breast cancer incorporating weekly gemcitabine administered as three-weeks-on, one-week-off schedule is widely adopted throughout the East Asia region. Hemolytic-uremic syndrome (HUS) associated with weekly gemcitabine for a breast cancer patient is extremely rare. We report here a case of 43-year-old woman with metastatic breast cancer who received weekly gemcitabine as a third-line palliative chemotherapy for her disease. She developed HUS after a cumulative dose of 11,000 mg/m 2 gemcitabine, evidenced by microangiopathic hemolytic anemia (MAHA) with schistocytes seen in peripheral blood smear, decreased haptoglobin level (0.29 mmol/L), thrombocytopenia, negative direct Coombs test, and acute kidney injury. Owing to the ease of administration of weekly gemcitabine, gemcitabine-induced thrombocytopenia, multifactorial anemia in metastatic breast cancer, and possibility of cancer progression, HUS could have gone unnoticed. Breast cancer oncologist should be cognizant of this rare HUS even during weekly gemcitabine treatment. KEY WORDS: breast neoplasms, gemcitabine, hemolytic-uremic syndrome CITATION: Kok et al. successful remission of hemolytic-Uremic syndrome during the third-line Weekly Gemcitabine for Metastatic Breast Cancer.

IntroductIon: Unlike autoimmune hemolytic anemia (AIHA), literature on the etiological study of non-autoimmune hemolytic anemia (non-AIHA) is scarce. The incidence and prevalence of non-AIHA in different geographic regions are largely unknown perhaps owing to the lack of perspective investigation and different profiles of etiologies from different geographic regions. We aimed to examine the real-world etiology or mechanisms of the nonhereditary non-AIHA from a nationwide population-based administrative claim database in Taiwan. PAtIents And methods: The National Health Insurance Research Database of Taiwan was adopted for this research. The studied population was total inpatient claim records including both pediatric and adult patients, contributed by a population of 23 million insured individuals in Taiwan. From 2002 to 2008, we retrieved 3,903 patients having no pre-existing malignancy discharged after inpatient management for acquired hemolytic anemia, which was defined as coding in discharge diagnoses containing ICD-9-CM code 283. By contrast, ICD-9-CM code 282 and all of the sub-codes are for hereditary hemolytic anemias. results: AIHA accounted for 32% of the total cases. Among 2,657 patients with non-AIHA, mechanical or microangiopathic mechanism accounted for 19% of cases; hemolytic-uremic syndrome (HUS) 4%, hemoglobinuria because of hemolysis from external causes such as paroxysmal nocturnal hemoglobinuria (PNH) and march hemoglobinuria 7%, and chronic idiopathic hemolytic anemia or other unspecified non-AIHA 69%. We looked further for specific etiology or mechanism for this group of patients with non-hereditary extrinsic non-AIHA (n = 2,657). The explanatory disease states or conditions were splenomegaly; alcohol use disorder (spur cell hemolysis); heart-valve prosthesis; malignant hypertension; disseminated intravascular coagulation; transfusion reaction; dengue fever-induced hemolytic anemia; direct parasitization; snake, lizard, or spider bite; and Wilson's disease with internal toxin mechanism. All these cases can explain up to 34.6% of all the non-hereditary extrinsic non-AIHA cases. Fragmentation hemolysis (HUS, heart-valve prosthesis, malignant hypertension, and disseminated intravascular coagulation) accounted for 7.4% of non-AIHA hospitalized patients with non-neoplastic disease. conclusIons: This article is the first one to clearly demonstrate that the non-neoplastic-induced HUS requiring hospitalization cases in Taiwan, which has a population of over 23 million were 110 over a span of seven years, 16 cases per year. Although the etiologies of non-AIHA are well known and described in the literature, this work added the statistical percentages of the various etiologies of non-AIHA in Taiwan. CitAtioN: Kok et al. Reappraisal of the etiology of extracorpuscular non-autoimmune acquired hemolytic anemia in 2657 hospitalized Patients with non-neoplastic disease.

Primary peritoneal cancers in pregnancy are rare. We report a case of metastatic peritoneal tumors associated with metastatic colon cancer and a primary peritoneal cancer in a 28-year-old, pregnant Taiwanese, P1. She had had some non-specific, but overlooked, gastrointestinal (GI) symptoms at her prenatal visits. Following cesarean delivery, she received a vigorous and multimodal strategy, including debulking surgery, adjuvant irradiation and intensive chemotherapy, but she died of the disease 2.5 years later. When we compared the prevalence of metastatic ovarian cancer in Taiwan, the most common sites of primary origin were found to be colorectal (50.4%), gastric (19.5%), breast (9.8%) and uterine cervix (9.8%). When we reviewed metastatic ovarian cancers at our hospital, we found more than half originated from the GI tract (58%) and we did not identify any metastatic cancer that originated from the breast. In conclusion, although malignant ovarian tumors in pregnancy are rare, it is important not to ignore any non-specific GI symptoms during prenatal visits.

Chronic inflammatory state is associated with accelerated atherosclerosis and resultant cardiovascular diseases (CVD) in the long run. The magnitude of the risk for CVD in patients with juvenile idiopathic arthritis (JIA) needs more research. We conducted a population-based retrospective cohort study to investigate the association of JIA and its anti-rheumatic therapy and subsequent cardiometabolic outcomes. Cox model was adopted to derive adjusted hazard ratios (aHR). We found that children with JIA (n = 2,399) harbors an increased risk for extracranial non-coronary arterial disorders with an aHR at 2.77 (95% confidence interval, 1.38-5.54, p < 0.004) than subjects without JIA (n = 11,456) after a mean follow-up duration of 6.53 (±1.22) years. This study also found elevated risks for dyslipidemia (aHR 1.69, 1.13 -2.54), adolescent diabetes (2.06, 1.17 -3.62) and gout (2.94, 2.13 -4.04) in children with JIA compared to non-JIA cohort. The risk for gout was elevated in every group of the JIA cohort with the greatest risk at 6.42 (2.61 -15.75) in children who received anti-TNF. With this short follow-up period, there were no increased risks for clinically evident myocarditis, hypertension, ischemic heart disease, heart failure, or cerebrovascular disease. )

Background
To investigate the association and magnitude of risk between JIA, its associated treatment and cancer development in Taiwanese children.

Methods
Nationwide population-based 1:4 age- and gender-matched retrospective cohort study was designed using the National Health Insurance Research Database of Taiwan. A cohort of 2,892 children <16 years old with JIA was formed as well as a non-JIA cohort of 11,568 in year 2003 to 2005. They were followed up till a diagnosis of malignancy or up to 8 years until 2010. Relative risk (RR), incidence rate ratio (IRR), and adjusted hazard ratio (aHR) of developing malignancy were calculated.

Results
The female to male ratio was 0.79:1. There were 3 cases of incident cancer in the “MTX use, biologics-naïve” group, only 1 in the anti-TNF biologics-containing group and 29 in the “both MTX- and biologics-naïve” group, in comparison, there were 50 cases of cancer in the non-JIA comparator group. During a 16114.16 patient-years follow-up, the RR and IRR for developing a malignancy in both methotrexate- and anti-tumor necrosis factor (TNF) biologics-naïve JIA children were 2.75 (95% confidence interval, 1.75 – 4.32) and 3.21 (2.01 – 5.05), respectively. For leukemia, the IRR was 7.38 (2.50 – 22.75); lymphoma, 8.30 (1.23 – 69.79); and soft tissue sarcoma, 11.07 (0.84 – 326.4). The IRR of other cancers was 2.08 (1.11 – 3.71). The aHR on cancer risk was 3.14 (1.98 – 4.98) in methotrexate- and biologics-naïve group. There were no statistically significant increased risk in JIA patients treated with methotrexate and/or anti-TNF biologics.

Conclusions
Compared with children without JIA, children with JIA have 3-fold increase of risk on malignancy in East Asia. Seemingly neither methotrexate nor anti-TNF biologics increases the risk further.

Introduction: Previous studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design.
Methods: Patients aged $40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483) groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index.
Results: With a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI), 1.08–1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95% CI, 1.10–1.41) in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73–0.95) for cardiovascular events compared with the allopurinol group.
Conclusions: The current population-based matched-cohort study did not support the association between allopurinol
therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.

Background: Recent studies have shown that inhaled corticosteroids (ICS) can exert anti-inflammatory effects for chronic airway diseases, and several observational studies suggest that they play a role as cancer chemopreventive agents, particularly against lung cancer. We aimed to examine whether regular ICS use was associated with a reduced risk for future malignancy in patients with newly diagnosed adult-onset asthma.
Methods: We used a population-based cohort study between 2001 and 2008 with appropriate person-time analysis. Participants were followed up until the first incident of cancer, death, or to the end of 2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer development. Kaplan–Meier cancer-free survival curves of two groups were compared.
Results: The exposed group of 2,117 regular ICS users and the nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5 years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation 2.4) person-years of follow-up for the ICS users and the comparator group of non-ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated at 1.33 with 95% confidence interval (CI), 1.00–1.76, P=0.0501. The Kaplan–Meier curves for overall cancer-free proportions of both groups were not significant (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular ICS use was conducted using “ICS-negative and chronic obstructive pulmonary disease (COPD)-negative” as the reference. The aHR for the group of “ICS-positive, COPD-negative” did not reach statistically significant levels with aHR at 1.38 (95% CI, 0.53–3.56). There was a statistically significant synergistic interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78 (95% CI, 2.10–6.81).
Conclusion: The protective effect of regular ICS use in the studied East Asian patients with adult-onset asthma was not detectable, contrary to reports of previous studies that ICS might prevent the occurrence of future cancer.

Background: The use of compassionate extubation (CE) to alleviate suffering by terminating mechanical ventilation and withdrawing the endotracheal tube requires professional adherence and efficiency. The Hospice Palliative Care Act, amended on January 9, 2013, legalizes the CE procedure in Taiwan.
Methods: From September 20, 2013 to September 2, 2014, the hospice palliative care team at a community hospital received 20 consultations for CE. Eight cases were excluded because of non-qualification. Following approval from the Ethics Committee, the medical records of the remaining 12 patients were reviewed and grouped by the underlying disease: A, “terminal-stage cancer”; B, “non-cancer out-of-hospital cardiac arrest”; and C, “non-cancer organ failure”. Time to extubation using a cut-off at 48 hours was assessed.
Results: The mean ages of patients (standard deviation) in groups A, B, and C were 66.3 (14.9) years, 72 (19.1) years, and 80.3 (4.0) years, respectively. The mean number of days of intubation at consultation were 6.8 (4.9), 7.3 (4.9), and 179.3 (271.6), respectively. The mean total doses of opioids (as morphine-equivalent dose) in the 24 hours preceding CE were 76 (87.5) mg, 3.3 (5.8) mg, and 43.3 (15.3) mg. The median times from extubation (range) to death were 97 (0.2–245)
hours, 0.3 (0.2–0.4) hours, and 6.1 (3.6–71.8) hours. Compared to those requiring 48-hour preparatory time, patients requiring 48 hours to the moment of CE were younger (62.8 years vs
75.5 years), required a mean time of 122 hours (vs 30 hours) to CE (P=0.004), had shorter length of stay (33.3 days vs 77.8 days), required specialist social worker intervention in 75% of cases (vs 37.5%), and had a median duration of intubation of 11.5 days (vs 5.5 days).
Conclusion: CE was carried out according to protocol, and the median time from extubation to death varies determined by the underlying disease which was 0.3 hour in patients admitted after out-of-hospital cardiac arrest and 97 hours in patients with advanced cancer.

OBJECTIVE:

Recent studies report a link between endometriosis and ovarian cancer (OC). Using a population-based cohort study to confirm the association between endometriosis and cancer is desirable. We thus examined the magnitude of the risks of OC, endometrial cancer (EC), breast cancer, colorectal cancer (CRC), and other cancers in women with newly diagnosed endometriosis or adenomyosis (internal endometriosis).

METHODS/MATERIALS:

Women older than 20 years with claims data between 2003 and 2005 were identified from the Longitudinal Health Insurance Dataset containing 1 million individuals randomly sampled from the National Health Insurance Research Database. Those with preexisting malignancies, hysterectomy, or oophorectomy were excluded. The endometriosis cohort (n = 2266, including 768 cases of pure adenomyosis) and comparison cohort (n = 9064), formed by 1:4 matching, were followed up until incidence cancer, dropout, or December 31, 2008. Outcome measures included cancer incidence and adjusted hazard ratio by Cox model adjusted for age group, comorbidities, and endometriosis medication use.

RESULTS:

With 9842 person-years of follow-up in endometriosis cohort and 36,274 person-years of follow-up in comparison cohort, there were increased risks of all cancers (adjusted hazard ratio, 1.8; 95% confidence interval, 1.4-2.4), OC (4.56, 1.72-12.11), and EC (4.05, 1.20-13.66). The ovarian endometriosis group was associated with increased risk of subsequent OC (4.37, 1.07-17.83). The adenomyosis group was strongly associated with both OC (5.50, 1.95-15.50) and EC (5.13, 1.36-19.40). Increased risk of subsequent CRC was observed in women with adenomyosis with coexistent endometriosis at other sites (13.04, 2.21-77.04). However, no statistically significant increased risk of breast or other cancers was observed.

CONCLUSIONS:

Having limitations such as lacking of parity information which may affect the magnitude of risk estimates, this study demonstrates that ovarian endometriosis has a 4-fold increased risk of OC. Adenomyosis may associate with a 4- to 5-fold increased risk of OC and EC, and unexpectedly, a 13-fold increased risk of CRC.

The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US
Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin) over two to five minutes on days 1
and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated.