HyperArcTM volumetric modulated arc therapy for hypopharyngeal cancer with solitary recurrence in the cervical vertebra: A case report and literature review.

RATIONALE: It is difficult to reirradiate head and neck cancers because of the toxicity from previous radiation dose delivery. Conventional volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy often have poor target coverage. The new HyperArcTM VMAT (HA-VMAT) planning approach reportedly has better target coverage, higher conformity, and can spare normal organs compared to conventional VMAT; however, research on recurrent head and neck cancers is limited. Here, we report the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence in the first cervical vertebra (C1). PATIENT CONCERNS: A 52-year-old Asian male was diagnosed with a hypopharyngeal cancer. The patient received concurrent chemoradiotherapy with a radiation dose of 70 Gy in 33 fractions and achieved complete clinical response. Two years later, solitary recurrence was observed in the C1 vertebra. DIAGNOSES: Solitary recurrence in the C1 vertebra. INTERVENTIONS: Owing to concerns regarding the toxicity to adjacent organs, we decided to use HA-VMAT to achieve better tumor coverage and critical organ sparing. OUTCOMES: Tumor regression was observed on the imaging. At 9 months follow-up, the patient was disease-free and had no late toxicities. LESSONS: This is the first report regarding the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence over the C1 vertebra. HA-VMAT achieves highly conformal dose distribution and excellent sparing of critical organs. There was a favorable initial clinical response with no toxicity. Long-term follow-up is essential in such cases.

The role of adjuvant radiotherapy for intracranial malignant meningiomas: analysis of a nationwide database.

PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.

Orodental malformations associated with human MSX1 sequence variants.

BACKGROUND: MSX1 sequence variants have been known to cause human tooth agenesis (TA) with or without orofacial clefts. However, their roles during the whole processes of tooth development are not fully understood. This study aimed to characterize a 4-membered family with TA carrying a novel MSX1 pathogenic variant and investigate the disease mechanism. METHODS: The authors conducted whole exome analysis to define the disease-causing sequence variant. They performed microcomputed tomography, morphometric analyses, transcriptome profiling, and molecular characterization to study the affected teeth and the gene variant. RESULTS: The authors identified an MSX1 pathogenic variant, p.Glu232∗, in affected family members with TA and concomitant orodental anomalies, namely, prominent maxillary labial frenum, central incisor diastema, median maxillary anterior alveolar cleft, tooth fusion, mandibular molar dysmorphology, thin dentin layer, and slender dental roots. MSX1-defective teeth were not apparently microdontic but had thin dentin layers. The mandibular molars showed a homeotic transformation to maxillary counterparts. Genes involved in extracellular matrix organization and dentinogenesis, such as DMP1 and MMP20, were downregulated in dental pulp tissues of MSX1-defective teeth. The p.Glu232∗-truncated MSX1 properly localized to the nucleus but partially lost its transactivation ability. Analyzing reported cases indicated that truncation sequence variants within the homeobox domain of MSX1 caused a more severe TA phenotype than those outside of the homeobox domain, probably due to dominant negativity compared with haploinsufficiency. CONCLUSIONS: This study provides in vivo evidence that MSX1 contributes to developmental processes of various orodental tissues in humans. PRACTICAL IMPLICATIONS: Clinically, hypertrophic labial frenum, incisor diastema, and median maxillary anterior alveolar cleft might be considered diagnostic for MSX1-associated TA.

Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis.

BACKGROUND: Genetic and epigenetic factors are strongly associated with the autoimmune disease rheumatoid arthritis (RA). Cyclic AMP response element modulator (CREM), a gene related to immune system regulation, has been implicated in various immune-mediated inflammatory processes, although it remains unknown whether CREM is involved in RA. METHODS: This study enrolled 278 RA patients and 262 controls. Three variants [rs12765063, rs17499247, rs1213386] were identified through linkage disequilibrium and expression quantitative trait locus analysis, and CREM transcript abundance was determined by quantitative real-time polymerase chain reaction. The identified variants were genotyped using the TaqMan Allelic Discrimination assay, and CREM promoter methylation was assessed by bisulphite sequencing. Differences between groups and correlations between variables were assessed with Student's t-tests and Pearson's correlation coefficients. Associations between phenotypes and genotypes were evaluated with logistic regression. RESULTS: Rheumatoid arthritis patients exhibited increased CREM expression (p < .0001), which was decreased by methotrexate (p = .0223) and biologics (p = .0001), but could not be attributed to CREM variants. Interestingly, rs17499247 displayed a significant association with serositis (p = .0377), and rs1213386 increased the risk of lymphadenopathy (p = .0398). Furthermore, seven CpG sites showed decreased methylation in RA (p = .0477~ p < .0001). CONCLUSIONS: Collectively, our results indicate that CREM hypomethylation and CREM upregulation occur in RA and that CREM variants are involved in the development of serositis and lymphadenopathy in RA. This study highlights the novel roles of CREM in RA pathophysiology.

Mucin 1 and interleukin-11 protein expression and inflammatory reactions in the intestinal mucosa of necrotizing enterocolitis children after surgery.

BACKGROUND: Necrotizing enterocolitis (NEC) of the newborn is a frequently occurring clinical disease in infants. The mortality rate of NEC in premature infants is as high as 50%, and the morbidity rate is on the rise. NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families. AIM: To investigate the expression and significance of mucin 1 (MUC1) and interleukin-11 (IL-11) in the intestinal mucosa of infants with neonatal NEC after surgery. METHODS: Forty-eight postoperative intestinal mucosal specimens from children with NEC (NEC group) and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia (control group) were collected in our hospital. Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups. The serum levels of tumor necrosis factor-α (TNF-α) and IL-1ß in the two groups were measured by enzyme-linked immunosorbent assay, and the relationship between MUC-1 and IL-11 protein expression and serum TNF-α and IL-1ß levels was analyzed by the linear correlation method. RESULTS: The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group, and the difference was statistically significant (P < 0.05). The levels of serum TNF-α and IL-1ß in the NEC group were significantly higher than those in the control group (P < 0.05). The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-α and IL-1ß levels (P < 0.05). There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-α and IL-1ß in the NEC group. CONCLUSION: The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery. This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.

Challenges of BCLC stage C hepatocellular carcinoma: Results of a single-institutional experience on stereotactic body radiation therapy.

In this study, we evaluated the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).This retrospective study evaluated 139 patients with BCLC stage C HCC who underwent CyberKnife SBRT between January 2009 and September 2017. All patients had BCLC-C, Child-Turcotte-Pugh score A-B. In-field control, overall survival (OS), progression free survival (PFS), and prognostic factors were evaluated.An objective response rate was achieved in 81.5% patients (complete response, 36.2%, partial response, 45.3%). The median survival was 15.44 months, and the 1-, 3-, 5-year OS rates were 56%, 28%, and 20%, respectively. The median PFS was 6 months, the PFS rate at 1-, 3-, and 5-year were 35%, 14%, and 10%, respectively. In-field control of 1 to 2 years was achieved in 85.1% of patients. The major pattern of failure was out-field intrahepatic failure which comprised 42.9% of patients. Multivariate analysis revealed that the Child-Turcotte-Pugh score, macrovascular invasion, advance stage (III-IV), and tumor response rate were independent predictors of OS.The result of our study shows that SBRT is a safe and effective therapeutic option for BCLC stage C HCC lesions that are unsuitable for standard loco-regional therapies, Moreover, SBRT has acceptable local control rates and low-treatment toxicity.

Hydrophobicity-Tuned Periodic Mesoporous Organo-Silica Nanoparticles for Photodynamic Therapy.

Since their invention, periodic mesoporous organosilicas (PMOs), an innovative class of materials based on organic as well as inorganic hybrid nanocomposites, have gathered enormous interest owing to their advantageous physicochemical attributes over the pristine mesoporous silica nanoparticles (MSNs). To further increase the interactions with the therapeutic guest species and subsequent compatibility as well as the physicochemical properties of PMOs, we demonstrate the post-hydroxylation of benzene-bridged PMO-based nanoparticles for photodynamic therapy (PDT). Initially, the hydrophobic benzene group in the PMO framework is modified through electrophilic substitution-assisted hydroxylation mediated by Fenton as well as Fenton-like reactions utilizing divalent and trivalent metal salts, respectively. These post-grafted PMOs with tuned hydrophobicity resulted in improved biocompatibility as well as drug loading efficiency through governing the interactions in host-guest chemistry by changing the physicochemical properties of the PMO frameworks. Furthermore, the photosensitizer, protoporphyrin IX (PpIX) molecules, encapsulated in the PMO frameworks showed a significant PDT effect in colon carcinoma (HT-29 cell line) and Gram-negative bacterial strain, Escherichia coli (E. coli). Furthermore, the light-induced cytotoxic properties in vitro are confirmed by various tests, including lactate dehydrogenase (LDH) assay for cell membrane damage and caspase assay for apoptosis determination. Indeed, the delivered PpIX molecules from PMOs generated deadly singlet oxygen species intracellularly under visible light irradiation, resulting in cell death through concomitantly triggered apoptotic caspases. Together, our findings demonstrate that this post-modified PMO design is highly advantageous and can be used as an effective PDT platform.

Induction Chemotherapy Improved Long Term Outcomes in Stage IV Locoregional Advanced Nasopharyngeal Carcinoma.

Purpose: We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). Methods: From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC added to CCRT or CCRT as the upfront treatment in all LANPC stage III and LANPC IV patients. The failure free survival (FFS), overall survival (OS), local relapse free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), first failure site, and other prognostic factors were analyzed. Results: The median follow-up time of all treated LANPC patients was 59 months. For all LANPC patients, there was a significant difference only in the DMFS favoring IC group (91.5% vs 79.4%, p=0.013). In the subgroup study, for the stage III group, there was no significant difference between the groups for overall OS (IC group 71.3% vs CCRT group 78.7%), FFS (71.5% vs 62.4%) and RRFS (91.9% vs 90.9%). However, inferior LRLS (71.7% vs 91.5%; p = 0.03) was noted for the IC group. In contrast, for stage IV, there were significantly longer OS (75.8% vs 52.6%), FFS (66.8% vs 46.8%), and DMFS (86.0% vs 69.6%; p = 0.02, p = 0.04, and p = 0.03, respectively) rates in the IC group. Conclusion: Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT.

Comparison of stereotactic body radiation therapy with and without sorafenib as treatment for hepatocellular carcinoma with portal vein tumor thrombosis.

Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for unresectable hepatocellular carcinoma (HCC) patients. However, the treatment outcomes for patients with portal vein tumor thrombosis (PVTT) remain poor. In this study, we evaluate the efficacy of SBRT with and or without sorafenib for advanced HCC with PVTT.Fifty four HCC patients with PVTT treated with SBRT using the Cyberknife system was retrospectively analyzed between January 2009 and June 2016. Of these, sorafenib combined with SBRT was administered to 18 patients and SBRT alone was administered to 36 patients. SBRT was designed to target the liver tumor and tumor thrombosis, with a radiation dose of 36 to 45 Gy (median 40 Gy) given in 3 to 5 fractions.The mean follow-up period for SBRT with sorafenib and SBRT alone was 13.22 ±â€Š10.07 months and 15.33 ±â€Š22.01 months, respectively. The response rate was comparable in both groups. Complete response and partial response rates were 77.77% for SBRT with sorafenib and 75.00% without sorafenib (P = .43). The median progression-free survival rate was 6 months (2-11 months) versus 3 months (2-5.6 months) (P = .24) and the 1- and 2-year progression-free survival rates were 25.7% and 15.2% versus 11.1% and 8.3% (P = .1225). The median, 1- and 2-year overall survival rates (OSR) were 12.5 months, 55.6% and 17.7% versus 7 months (5-13.5 months), 33.3% and 11.1% (P = .28), for SBRT with sorafenib versus SBRT alone groups, respectively.The result of our study shows that SBRT with sorafenib administered group resulted in a higher median, progression-free, and OSR for HCC patients with PVTT. However, the trends did not attain statistical significance. A large-scale randomized study is needed to assess the benefits of SBRT with sorafenib administration for patient with PVTT.

A seven-year experience of using moderate deep inspiration breath-hold for patients with early-stage breast cancer and dosimetric comparison.

We present our seven-year experience of using moderate deep inspiration breath-hold (mDIBH) with an active breathing control (ABC) device for patients with early-stage breast cancer and dosimetric comparison to evaluate the benefit of mDIBH on the heart, lung, and liver.We retrospectively reviewed all patients with newly diagnosed breast cancer and having clinical stage Tis, I, or II disease treated between November 2010 and October 2017. Among the 369 patients included in this study, 107 patients were treated with mDIBH and 262 patients were treated with free breathing (FB). Dosimetric analysis was performed to compare dose distribution in the heart, lung, and liver between the two treatment groups. The chi-square test was used to compare the distribution of stage and tumor site between the two groups. The independent samples t-test was used to compare the remaining parameters between the two groups.For all 369 patients, there was a significantly lower ipsilateral lung V5 (relative volume receiving ≧5 Gy), ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V5, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, and mean heart dose in the mDIBH group. For 184 patients with a left-sided breast tumor, significantly lower ipsilateral lung V5, ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, and mean heart dose were observed in the mDIBH group. For 185 patients with a right-sided breast tumor, significantly lower ipsilateral lung V5, ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V5, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, mean heart dose, liver V30, and mean liver dose were observed in the mDIBH group.For early-stage breast cancer patients, mDIBH reduces not only the heart dose but also the lung and liver doses. The routine integration of mDIBH using an ABC device may decrease radiation-induced toxicity in the heart, lung, and liver.

Role of Salivary Immune Parameters in Patients With Primary Sjögren's Syndrome.

BACKGROUND: Several factors, including clinical manifestations and laboratory data, have been used to evaluate the disease activity of Sjögren's syndrome (SS). We investigated saliva indicators of disease activity in primary SS patients. METHODS: We enrolled 138 Taiwanese patients with primary SS and 100 Taiwanese normal controls. Interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha (TNF-α), and rheumatoid factor (RF)-IgA levels in saliva samples were measured using ELISA or fluorescent enzyme-linked immunoassay. Serum IgG, IgA, and IgM levels were measured by nephelometry. Erythrocyte sedimentation rate (ESR) was measured with an automatic ESR analyzer. The t-test and Pearson correlation test were used. RESULTS: IL-6 level was higher in primary SS patients than in normal controls (14.23±14.77 vs 9.87±7.32, P=0.012), but there were no significant differences in IL-17A, TNF-α, and RF-IgA levels. In primary SS patients, IL-6 level correlated weakly with ESR and IgG levels (r=0.252, P=0.015, and r=0.248, P=0.017, respectively), and TNF-α level correlated weakly with IgG level (r=0.231, P=0.024). CONCLUSIONS: IL-6 may play a role in SS pathogenesis. Saliva IL-6 might be an indicator of disease activity in primary SS patients.

Evaluating the optimal radiation dose for definitive chemoradiotherapy for esophageal squamous cell carcinoma: A single institution experience.

The optimal radiation dose for definitive chemoradiotherapy in inoperable esophageal squamous cell carcinoma (ESCC) has been long debated. In this study, we evaluated the effect of doses greater than the conventional radiation dose (50.4 Gy) on tumor control, tumor response, overall survival (OS), and disease-free survival (DFS).The database of patients diagnosed with inoperable ESCC from 2007 to 2015 was obtained from the cancer registry of Chi-Mei Medical Center. All categorical variables were compared using Chi-squared test. The risk of OS and DFS were estimated using Cox proportional hazards regression, and Kaplan-Meier plots presented the trend of OS and DFS with log-rank tests used to compare differences. All significance levels were set at P < .05.A total of 84 patients were retrospectively analyzed, with 42 (50%) receiving >50.4 Gy and 42 (50%) receiving ≤50.4 Gy (50%) concurrently with chemotherapy. Univariate and multivariate analysis revealed no significant differences between higher dose and conventional dose in OS (P = .21) and DFS (P = .26). Further dose analysis of <50, 50 to 50.4, 51 to 60, and >60 Gy showed no significant differences in OS or DFS. Higher doses conveyed no significant benefit on the failure pattern, either local regional failure or distant failure (P = .42). Major prognostic factors associated with better OS on multivariate analysis were stages I and II patients (P = .03) and radiation technique using arc therapy (P = .04). No acute toxicity of grade III or higher was recorded.The results of our study show that providing higher than conventional radiation doses concurrent with chemotherapy for inoperable ESCC does not impact OS or DSF, nor does it improve locoregional failure or distant failure. Although tumor response might be improved by radiation doses >50.4 Gy, the impact on OS and DFS remain to be studied.

[The Relationship Between Pain and Demoralization in Cancer Patients].

BACKGROUND: While patients with cancer commonly experience bodily pain, their perceptions of this pain may differ. Continually experiencing pain elicits a sense of helplessness and pessimism in these patients and exacerbates their perception of interpersonal alienation, which may cause the demoralization syndrome. In Taiwan, the rate of demoralization among patients with cancer is substantially higher than that in other countries. PURPOSE: The meaning of cancer pain is used as the mediating variable to investigate the relationship between the pain that is experienced by patients with cancer and their demoralization. METHODS: Sixty cancer patients were surveyed using convenience sampling. Data were collected using the Taiwanese version of the Brief Pain Inventory, the Mandarin version of the Demoralization Scale, and the Perceived Meanings of Cancer Pain Inventory. The primary statistical analysis method used was path analysis. RESULTS: (1) The extent to which pain disrupted the daily life of the participants directly affected their demoralization and perceived meanings of pain. (2) For the patient group that experienced the least pain, the extent to which pain disrupted daily life increased their demoralization scores, with this increase mediated by their perceived meaning of pain as "being threatened." (3) For the patient group that experienced the most pain, the extent to which pain disrupted daily life and to which they perceived the meaning of pain as "a challenge" indirectly affected their demoralization scores. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Cancer care should not only alleviate patient pain but also emphasize the effect of pain on disrupting the daily life of patients and eliciting their sense of demoralization. This enables the early diagnosis of the demoralization syndrome. Care may be provided in accordance with the various meanings of pain that are perceived by cancer patients. When patients perceive pain as a challenge, they are unlikely to be demoralized. However, when patients perceive pain as a threat, attention should be paid to their sense of demoralization.

Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma.

Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor size on treatment outcomes after SBRT.Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4-<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed.A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival.SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate.

Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology. METHODS: Between 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models. RESULTS: The median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 %(54-71.5 %) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 %(33.0-52.2 %) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3-16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2-91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out-field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 %(38.9-59.2 %), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (≤4 cm vs >4-9 cm /≥10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable. CONCLUSIONS: Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment.

F11R mRNA expression and promoter polymorphisms in patients with rheumatoid arthritis.

AIM: Although F11 receptor (F11R), also named junctional adhesion molecular A (JAM-A), participates in leukocyte migration, its role in autoimmune diseases has not been specifically disclosed. In this study, we examined the association of F11R expression with the development and clinical manifestations of rheumatoid arthritis (RA). METHOD: RNA from peripheral blood mononuclear cells (PBMCs) and DNA from the peripheral blood in RA patients and a healthy control group were extracted. F11R messenger RNA (mRNA) expression was determined by quantitative real-time polymerase chain reaction. The F11R polymorphisms were determined by the TaqMan genotyping assay. RESULTS: There was more F11R mRNA expression in the PBMCs of RA patients than those of the control group (P = 0.018). In F11R promoter -688 A > C, C carriers have lower titers of the anticyclic citrullinated peptide (anti-CCP) antibodies (P = 0.002) and fewer positive rates of Schirmer's tests (P = 0.009). The effect is independent of the existence of HLA-DR4. Different genotypes in F11R promoter -688 A > C and -436 A > G do not lead to changes of the gene expression in RA patients. CONCLUSION: RA patients have higher mRNA expression of F11R. In RA patients, F11R -688 C may be a protective factor for the development of anti-CCP antibodies and positive rates of Schirmer's tests.

The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities.

BACKGROUND AND AIM: To evaluate the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients with unresectable huge hepatocellular carcinoma (HCC) unsuitable of other standard treatment option. METHODS: Between 2009 and 2011, 22 patients with unresectable huge HCC (≧10 cm) were treated with SBRT. dose ranged from 26 Gy to 40 Gy in five fractions. Overall survival (OS) and disease-progression free survival (DPFS) were determined by Kaplan-Meier analysis. Tumor response and toxicities were also assessed. RESULTS: After a median follow-up of 11.5 month (range 2-46 months). The objective response rate was achieved in 86.3% (complete response (CR): 22.7% and partial response (PR): 63.6%). The 1-yr. local control rate was 55.56%. The 1-year OS was 50% and median survival was 11 months (range 2-46 months). In univariate analysis, Child-Pugh stage (p = 0.0056) and SBRT dose (p = 0.0017) were significant factors for survival. However, in multivariate analysis, SBRT dose (p = 0.0072) was the most significant factor, while Child-Pugh stage of borderline significance. (p = 0.0514). Acute toxicities were mild and well tolerated. CONCLUSION: This study showed that SBRT can be delivered safely to huge HCC and achieved a substantial tumor regression and survival. The results suggest this technique should be considered a salvage treatment. However, local and regional recurrence remain the major cause of failure. Further studies of combination of SBRT and other treatment modalities may be reasonable.

Prenatal diagnosis of proximal femoral focal deficiency: a case report and literature review.

OBJECTIVE: To present a rare case of fetal nonfamilial proximal femoral focal deficiency (PFFD) diagnosed as early as 21 weeks' gestation. CASE REPORT: A 32-year-old woman was referred to our hospital at 21 weeks' gestation. An ultrasound examination revealed isolated unilateral short femur (right femur = 27.3 mm and left femur = 37.9 mm). The measurements of all the remaining long bones were within the normal range. The facial profile was unremarkable. Results of amniocentesis revealed a normal 46,XX female karyotype. A follow-up ultrasound 2 weeks later demonstrated further discrepancy in femoral length. A diagnosis of PFFD was made. The parents were well informed about the treatment options and after counseling they decided to terminate the pregnancy. A postmortem X-ray examination confirmed the diagnosis of PFFD. CONCLUSION: We have to measure both sides of extremities according to the ultrasound scan guidelines so as not to overlook any possible case of skeletal dysplasia. An advanced three-dimensional (3D) and 4D ultrasound evaluation of the bony structures and carefully observing the range of mention of the affect limbs will provide proper information to formulate a further therapeutic plan.

Utilization and patterns of community healthcare services for senior residents in long-term care facilities in Taiwan: a nationwide study.

BACKGROUND: Community healthcare is one of the many important services used to care for the disabled elderly in aging societies. The aim of this study was to evaluate the utilization and patterns of community healthcare services used by senior residents in long-term care facilities (LTCFs) in Taiwan. METHODS: Secondary data analyses were conducted of the Taiwan National Health Insurance Research Database for 9338 LTCF senior residents receiving community healthcare services throughout the 2004 calendar year. The community healthcare services used by male and female LTCF senior residents were also compared by Chi-square testing. Descriptive statistics are used to present the patterns of professional visits and services by contracted healthcare facilities. RESULTS: About one-third of those senior residents living in LTCFs in Taiwan in 2004 received community healthcare services. Female residents received a higher percentage of community healthcare services than males in all age groups (p<0.001). Community home nursing care institutions provided 67% of healthcare visits and professional visits. Of those services provided to patients, the majority of the skilled nursing services were attributable to replacement of nasogastric tube (55%) and urinary catheter (38%). CONCLUSION: Whether or not the replacement of nasogastric tubes and urinary catheters among the LTCF senior resident population is an appropriate use of time and targeted medical resources needs further investigation. When addressing concerns about the community healthcare needs of senior residents of LTCFs, policymakers should carefully consider the current shortage of professional healthcare workers as they assess strategies to best meet the needs of the elderly in Taiwan.

Do transition-metal substitutions dope carriers in iron-based superconductors?

We investigate the currently debated issue concerning whether transition-metal substitutions dope carriers in iron-based superconductors. From first-principles calculations of the configuration-averaged spectral function of BaFe2As2 with disordered Co or Zn substitutions of Fe, important doping effects are found beyond merely changing the carrier density. While the chemical potential shifts suggest doping of a large amount of carriers, a reduction of the coherent carrier density is found due to the loss of spectral weight. Therefore, none of the change in the Fermi surface, density of states, or charge distribution can be solely used for counting doped coherent carriers, let alone presenting the full effects of the disordered substitutions. Our study highlights the necessity of including disorder effects in the studies of doped materials in general.