Therapeutic Decision-Making Using Endoscopic Ultrasonography in Endoscopic Treatment of Early Gastric Cancer

Background/Aims

We evaluated the effectiveness of an endoscopic ultrasonography (EUS)-based treatment plan compared to an endoscopy-based treatment plan in selecting candidates with early gastric cancer (EGC) for endoscopic submucosal dissection based on the prediction of invasion depth.

Methods

We reviewed 393 EGCs with differentiated histology from 380 patients who underwent EUS from July 2007 to April 2010. The effectiveness of the EUS-based and endoscopy-based plans was evaluated using a simplified hypothetical treatment algorithm.

Results

The numbers of endoscopically determined mucosal, indeterminate, and submucosal cancers were 253 (64.4%), 56 (14.2%), and 84 (21.4%), respectively. Overall, the appropriate treatment selection rates were 75.3% (296/393) in the endoscopy-based plan and 71.5% (281/393) in the EUS-based plan (p=0.184). For endoscopic mucosal cancers, the appropriate treatment selection rates in the endoscopy-based plan were 88.1% (223/253), while the use of an EUS-based plan significantly decreased this rate to 81.4% (206/253) (p=0.036). For endoscopic submucosal cancers, the appropriate selection rates did not differ between the endoscopy-based plan (46.4%, 39/84) and the EUS-based plan (53.6%, 45/84) (p=0.070).

Conclusions

EUS did not increase the likelihood of selecting the appropriate treatment in differentiated-type EGC. Therefore, EUS may not be necessary before treating differentiated-type EGC, especially in endoscopically presumed mucosal cancers.     

Comparison of 1-Year Colectomy Risk Between the US and Korean Patients with Acute Severe Ulcerative Colitis: A Propensity Score Matching Analysis

Digestive Diseases and Sciences - Colectomy risk after acute severe ulcerative colitis (ASUC) has not been compared between Eastern and Western countries. We compared the 1-year colectomy risk...     

Decreased Serum Epinephrine in Children With Positive Skin Prick Test

Objectives

To evaluate the association between catecholamine levels and skin prick test results among children.

Methods

Two hundred eight first grade children from one elementary school were invited to participate in this study. Skin prick test (SPT) for six allergens (2 house dust mites, cat, dog, mugwort, and pollen mixture) was performed, and patient demographic information was recorded. The parents were surveyed using questionnaires about rhinitis-related symptoms. Finally, venous blood sampling was done to measure catecholamine levels (epinephrine, norepinephrine, and dopamine) by high-performance liquid chromatography.

Results

Out of 208 children, 174 (106 boys and 68 girls) enrolled in this study. Ninety-six of the children (55%) had negative SPT (nonsensitization group), while 78 (45%) had a positive SPT to at least one of six allergens (sensitization group). The diagnosis of chronic rhinitis was more prevalent in the sensitization group (35.9%) than nonsensitization group (26.0%), however the finding was not significant (P=0.186). Epinephrine levels were decreased between the sensitization group compared to the nonsensitization group (P=0.004). There was no difference in norepinephrine and dopamine levels (P>0.05).

Conclusion

Epinephrine levels are lower in children with positive SPT compared to controls, however, the level of the catecholamine was not associated with the presence or absence of rhinitis symptoms.     

Practice-Based Research Priorities for Palliative Care: Results From a Research-to-Practice Consensus Workshop

We employed the research-to-practice consensus workshop (RTP; workshops held in New York City and Tompkins County, New York, in 2013) model to merge researcher and practitioner views of translational research priorities in palliative care. In the RTP approach, a diverse group of frontline providers generates a research agenda for palliative care in collaboration with researchers. We have presented the major workshop recommendations and contrasted the practice-based research priorities with those of previous consensus efforts. We uncovered notable differences and found that the RTP model can produce unique insights into research priorities. Integrating practitioner-identified needs into research priorities for palliative care can contribute to addressing palliative care more effectively as a public health issue.Over the past 2 decades, palliative care has become established as a promising approach for addressing the needs of individuals with life-threatening illnesses from a holistic, interdisciplinary perspective. For this project, we defined palliative care as an approach that improves the quality of life of patients and families facing the problems encountered in life-threatening illness by preventing and relieving suffering. Core components of palliative care include providing relief from pain and other distressing symptoms, affirming dying as a normal process, integrating psychological and spiritual aspects of care, enhancing the quality of life of patients, and offering support systems to patients and their families to help them live as fully as possible until death occurs.Research suggests that palliative care results in positive patient outcomes, greater patient and family satisfaction, and significant cost savings.1,2 The American Public Health Association, the World Health Organization, and the Institute of Medicine3–6 have identified the development of a robust palliative care delivery system as a key public health issue because of the documented ability of palliative care to deliver effective and efficient patient- and symptom-focused care to a growing population in need.In its 2013 report the American Public Health Association specifically detailed the public health implications of palliative care, acknowledged the growing burden of advanced chronic illness and disease in older adults, and recommended key steps to address the problem. This policy statement called for federal, state, and local efforts to promote effective symptom management in populations with serious illness or at the end of life. Other recommended initiatives included the development of a palliative care workforce, educational programs to improve uptake and use of palliative and hospice care, and research funding to support the expansion of palliative care initiatives. Achieving these goals will require moving beyond traditional medical practices to include both policies and initiatives at the public health level.Despite the potential of palliative care to address the mental and physical health needs of individuals with advanced illness, significant knowledge gaps impede its reach and effectiveness. Reports from scientific bodies and consensus workshops have highlighted weaknesses in the literature and called for more research on palliative care and improved research methods.7–10 Thus, although both interest in and demand for palliative care are increasing, reviews of the knowledge base continue to lament the lack of research on many key issues.11,12Especially urgent is a research agenda that fits most closely with the needs of providers who deliver palliative care. The systematic engagement of community practitioners in a consensus process can lead to particularly useful and actionable recommendations for research,13–15 which are greatly needed at this stage in the development of the field. Therefore, to shed new light on research priorities in palliative care, we used a structured, participatory method designed to solicit practitioner input on research priorities: the research-to-practice consensus workshop (RTP) model.16We employed the RTP approach to identify knowledge gaps and types of studies that should be conducted to improve providers’ ability to deliver palliative care most effectively. This model harnesses practice wisdom by engaging clinicians, agency staff, and other practitioners with researchers in a process of articulating and refining research questions and research priorities that honors scientific expertise and practice wisdom.     

Macrolides increase the expression of 11β‐hydroxysteroid dehydrogenase 1 in human sinonasal epithelium,contributing to glucocorticoid activation in sinonasal mucosa

Background and Purpose

The anti‐inflammatory and immunomodulatory effects of macrolides include the ability to decrease mucus secretion and inhibit inflammatory mediators in chronic rhinosinusitis. Nevertheless, their mechanisms of action remain to be determined. Here we have investigated the effects of macrolide antibiotics (clarithromycin, azithromycin and josamycin; representating the 14‐, 15‐ and 16‐membered macrolides) on endogenous steroids in human sinonasal epithelial cells and mouse nasal mucosa.

Experimental Approach

The effects of macrolides on the expression of steroid‐converting enzymes [11β‐hydroxysteroid dehydrogenase (11β‐HSD1 and 11β‐HSD2)], steroid‐synthesizing enzymes (3β‐HSD, CYP21, CYP11B1 and CYP11A1) and cortisol levels were assessed in cultured human epithelial cells. In control and adrenalectomized mice , these enzymes and corticosterone levels were evaluated in nasal mucosa and serum after administration of macrolides.

Key Results

The expression levels of 3β‐HSD, CYP21, 11β‐HSD1 and CYP11B1 increased in human epithelial cells treated with clarithromycin and azithromycin, whereas the expression levels of 11β‐HSD2 and CYP11A1 were not affected. Josamycin had no effects on the expression of these enzymes. Cortisol levels increased in epithelial cells treated with clarithromycin or azithromycin. The expression of 3β‐HSD, CYP11A1, CYP21, CYP11B1 and 11β‐HSD1 was upregulated in nasal mucosa of mice treated with clarithromycin or azithromycin, but not in adrenalectomized mice.

Conclusions and Implications

This study provides evidence that 14‐ and 15‐membered macrolide antibiotics may affect the expression of steroid‐synthesizing and steroid‐converting enzymes in human sinonasal epithelial cells and mouse nasal mucosa, increasing the endogenous cortisol levels in sinonasal mucosa.

Abbreviations

11β‐HSD1

11β‐hydroxysteroid dehydrogenase 1

11β‐HSD2

11β‐hydroxysteroid dehydrogenase 2

3β‐HSD

3β‐hydroxysteroid dehydrogenase

CYP21A1

cytochrome P450, family 21, subfamily A, polypeptide 1

CYP11B1

cytochrome P450, family 11, subfamily B, polypeptide 1

CYP11A1

cytochrome P450, family 11, subfamily A, polypeptide 1

CRS

chronic rhinosinusitis

PBS‐T

phosphate‐buffered saline‐Tween 20

PF

915275, N‐(6‐amino‐2‐pyridinyl)‐4''‐cyano‐[1,1''‐biphenyl]‐4‐sulfonamide

siRNA

small interfering RNA

     

Clinical significance of CT-defined minimal ascites in patients with gastric cancer

AIM: To study the clinical significance of minimal ascites, which was only defined by the CT and whose nature was not determined preoperatively, in the relationship with the peritoneal carcinomatosis. METHODS: The medical records and the dynamic CT films of 118 patients with gastric cancer were reviewed. Factors associated with peritoneal carcinomatosis were analyzed in 40 patients who had CT-defined ascites of which the nature was surgically confirmed. RESULTS: Only 12.5-25% of the CT-defined minimal ascites, whose volume was estimated to be less than 50 mL, were associated with peritoneal carcinomatosis. When the estimated CT-defined ascitic volume was 50 mL or more, peritoneal carcinomatosis was identified in 75-100%. When CT-defined lymph node enlargements were not found beyond the regional gastric area, perigastric invasions were not suspected, and the size of tumor was less than 3 cm, peritoneal carcinomatosis seemed significantly less accompanied at the univariate analysis. However, except for the minimal volume of CT-defined ascites in comparison with the mild or more, other factors were not confirmed multivariately. CONCLUSION: In the patients with gastric cancer, CT-defined minimal ascites alone is rarely associated with peritoneal carcinomatosis, if it does not accompany other signs suggestive of malignant seeding. Therefore, consideration of active curative resection should not be hesitated, if CT-defined minimal ascites is the only delusive sign.     

Adult patients with t(8;21) acute myeloid leukemia had no superior treatment outcome to those without t(8;21): a single institution’s experience

Clinical features and treatment outcome of 31 patients over 16 years of age with t(8;21) acute myeloid leukemia (AML) were compared with 60 patients without t(8;21). Among 31 patients with t(8;21), 15 patients were classified as AML-M2 and 11 and 5 patients as AML-M4 and M1, respectively. Of these patients, 28 patients (90.3%) achieved complete remission and 22 patients received consolidative treatment: intermediate-dose cytarabine (IDAC) 11, high-dose cytarabine (HDAC) 6, and allogeneic bone marrow transplantation (BMT) 5. When compared with patients without t(8;21), we could not demonstrate better treatment outcome for t(8;21) AML [median event-free survival (EFS) and overall survival (OS) 10.3 and 12.5 months in AML with t(8;21) vs 11.5 and 15.6 months in AML without t(8;21)]. In the t(8;21) AML group, patients who received HDAC consolidation did not show superior treatment outcome to those who received other consolidative treatment [median EFS: IDAC 11.9 months vs HDAC 9.2 months vs allogeneic BMT 38.1 months (P=NS) and median OS: IDAC 17.8 months vs HDAC 12.0 months vs allogeneic BMT 47.3 months (P=NS)]. Similar treatment outcome between patients with and without t(8;21) and non-superior treatment outcome of HDAC consolidative chemotherapy in the t(8;21) AML group in our study is contradictory to previous reports.These two authors equally contributed to this study: K.-W. Lee and I. S. ChoiSupported by a grant CRI-01-07 from the Cancer Research Institute, Seoul National University College of Medicine, and a grant 05-2001-002 from the S.N.U.H. Research Fund     

Telomerase activity in acute myelogenous leukaemia: clinical and biological implications

We examined telomerase activity in myeloid leukaemic cell lines, normal haemopoietic cells, and leukaemic blasts from acute myelogenous leukaemia (AML) patients. Normal bone marrow mononuclear (BMNC) cells expressed low telomerase activity. Higher telomerase activity was detected in 10 myeloid leukaemic cell lines compared to normal BMNC cells. Treatment with 1,25(OH)₂D₃, and vitamin D₃ analogues, EB1089 and KH1060, reduced telomerase activity in vitamin D₃-sensitive HL-60 cells, whereas vitamin D₃ insensitive K562 cells did not change its activity. This down-regulation of telomerase activity by EB1089 was associated with induction of p21 protein. The rank order of telomerase activity was leukaemic CD34⁻ cells > leukaemic CD34⁺ cells > normal CD34⁻ cells > normal CD34⁺ cells. Telomerase activity was positive in all of the AML patients tested; however, heterogeneity of telomerase activity was found amongst this group. Therefore we compared telomerase activity with clinical response. Unexpectedly, we found that a higher rate of complete remission was noted in AML patients with higher telomerase activity. No association between telomerase activity and biological parameters including percentage of S-phase, cytotoxicity to cytosine arabinoside and percentage of CD34⁺ cells in AML blasts was found. These results suggest that telomerase activity in AML patients is detected with high frequency, but is heterogenous. Expression level of telomerase activity may have a clinical implication in AML patients regarding clinical response.