J.S. Heo

Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist's view

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Paraquat Prohibition and Change in the Suicide Rate and Methods in South Korea

The annual suicide rate in South Korea is the highest among the developed countries. Paraquat is a highly lethal herbicide, commonly used in South Korea as a means for suicide. We have studied the effect of the 2011 paraquat prohibition on the national suicide rate and method of suicide in South Korea. We obtained the monthly suicide rate from 2005 to 2013 in South Korea. In our analyses, we adjusted for the effects of celebrity suicides, and economic, meteorological, and seasonal factors on suicide rate. We employed change point analysis to determine the effect of paraquat prohibition on suicide rate over time, and the results were verified by structural change analysis, an alternative statistical method. After the paraquat prohibition period in South Korea, there was a significant reduction in the total suicide rate and suicide rate by poisoning with herbicides or fungicides in all age groups and in both genders. The estimated suicide rates during this period decreased by 10.0% and 46.1% for total suicides and suicides by poisoning of herbicides or fungicides, respectively. In addition, method substitution effect of paraquat prohibition was found in suicide by poisoning by carbon monoxide, which did not exceed the reduction in the suicide rate of poisoning with herbicides or fungicides. In South Korea, paraquat prohibition led to a lower rate of suicide by paraquat poisoning, as well as a reduction in the overall suicide rate. Paraquat prohibition should be considered as a national suicide prevention strategy in developing and developed countries alongside careful observation for method substitution effects.

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder

BACKGROUND Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. METHODS We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. RESULTS Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. LIMITATIONS TSH was only measured at baseline. CONCLUSIONS Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD.

The outcomes after surgical resection in pancreatic endocrine tumors: An institutional experience

AIM Sporadic pancreatic endocrine tumors (PET) can be managed surgically with excellent outcomes. The aim of this study was to analyze surgical outcomes and factors influencing survival. METHODS Between 1995 and 2007, 96 patients with sporadic PET who underwent surgery at our institution were retrospectively reviewed for clinicopathologic variables and outcomes according to the World Health Organization (WHO) classifications. RESULTS Thirty-nine patients had well-differentiated tumors (WDT) with benign behavior, 23 had uncertain behavior, 27 had low-grade carcinoma, and 7 were diagnosed with high-grade carcinoma. R0 resection was performed in 84 patients. No recurrence was observed in WDT regardless of its behavior or curability but 16 of 34 patients with carcinoma had recurrence. Five-year overall survival (OS) for R0-resected patients with carcinoma was 57%, and OS at 3 years for R1/R2-resected patients was 23% (P = 0.012). The WHO classification and R0 resection were independent prognostic factors in multivariate analysis. CONCLUSIONS This single institutional experience demonstrated that surgical resection is curative for WDT and recurrences are frequent in spite of curative resection for malignant PET. The WHO classification and R0 resection remained independent prognostic factor.

Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: a 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study.

Abstract Although many patients with major depressive disorder (MDD) complain of neurocognitive impairment, the effects of antidepressant medications on neurocognitive functions remain unclear. This study compares neurocognitive effects of tianeptine and escitalopram in MDD. Patients with MDD (N = 164) were randomly assigned in a 1:1 ratio to either tianeptine (37.5 mg/d) or escitalopram (10 mg/d) for 12 weeks. Outcome measures included clinical improvement, subjective cognitive impairment on memory and concentration, the Mini–Mental State Examination, the Continuous Performance Test, the Verbal Learning Test, and the Raven Progressive Matrices, assessed every 4 weeks. After 12 weeks, the tianeptine group showed significant improvement in commission errors (P = 0.002), verbal immediate memory (P < 0.0001), Mini–Mental State Examination (P < 0.0001), delayed memory (P < 0.0001), and reasoning ability (P = 0.0010), whereas the escitalopram group improved in delayed memory and reasoning ability but not in the other measures. Both groups significantly improved in subjective cognitive impairment in memory (P < 0.0001) and concentration (P < 0.0001). Mixed effects model repeated measures analyses revealed that the tianeptine group had a significant improvement in scores of commission errors (F = 6.64, P = 0.011) and verbal immediate memory (F = 4.39, P = 0.038) from baseline to 12 weeks, compared with the escitalopram group, after controlling for age, sex, education years, baseline scores, and changes of depression severity. The treatment of MDD with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram, after controlling for changes in depression severity. Both drugs improved subjective cognitive impairment of memory and concentration.

Childhood trauma, parental death, and their co-occurrence in relation to current suicidality risk in adults: a nationwide community sample of korea

Abstract Although previous studies have suggested that childhood trauma and parental death are strongly associated with suicidality in adulthood, it is still unclear how these factors interact within the same population. A total of 1396 adults were recruited through nationwide multistage probability sampling in South Korea. Subjects were evaluated through face-to-face interviews using the Suicidality Module of the Mini-International Neuropsychiatric Interview and the Early Trauma Inventory Self Report-Short Form. Among the 1396 adults, the group that experienced both childhood trauma and parental death had the highest current suicidality risks (F = 12.16, p < 0.0001) and lifetime suicide attempt (&khgr;2 = 35.81, p < 0.0001) compared with the other groups, which were only childhood trauma, only parental death, and neither. Multivariate logistic regression analyses revealed that middle-to-high current suicidality risk and lifetime suicide attempt were significantly associated with concurrent childhood trauma and parental death (odds ratio, 3.64; 95% confidence interval, 1.99–6.65) as well as with only childhood trauma (odds ratio, 1.95; 95% confidence interval, 1.33–2.87), after adjusting for age, sex, education, marital status, household monthly income, and living area. Emotional abuse was the only type of childhood trauma significantly associated with higher current suicidality scores in those who experienced childhood parental death than in those who did not (F = 3.26, p = 0.041). Current suicidality risk and lifetime suicide attempt are associated with experiencing both parental death and trauma, especially emotional abuse, in childhood, whereas experiencing only childhood parental death is associated with neither.

Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder

Objective Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD). Methods A total of 709 patients who were newly diagnosed with MDD were recruited. Anxiety levels of participants were evaluated using the Anxiety/ Somatization subitem of the Hamilton Depression Rating Scale. The association between WBC subset fraction and anxiety was evaluated. Results Basophil and eosinophil sub-fractions showed significant negative correlations with HAM-D anxiety/somatization factor scores (basophils: r=-0.092, p=0.014 and eosinophils: r=-0.075, p=0.046). When an anxiety score (a sum of somatic and psychic anxiety) was entered as a dependent variable, only basophils showed significant negative association with the anxiety scores after adjusting for all other WBC subset counts and demographic factors (t=-2.57, p=0.010). Conclusion This study showed that anxious depression had a decreased basophil subfraction, which might be associated with involvement of inflammation in development of anxious depression.

Review of Cohort Studies for Mood Disorders

This paper aimed to review currently available cohort studies of subjects with mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD). Using the PubMed and KoreaMed databases, we reviewed eight major cohort studies. Most studies recruited participants with MDD and BD separately, so direct comparison of factors associated with diagnostic changes was difficult. Regular and frequent follow-up evaluations utilizing objective mood ratings and standardized evaluation methods in a naturalistic fashion are necessary to determine detailed clinical courses of mood disorders. Further, biological samples should also be collected to incorporate clinical findings in the development of new diagnostic and therapeutic approaches. An innovative cohort study that can serve as a platform for translational research for treatment and prevention of mood disorders is critical in determining clinical, psychosocial, neurobiological and genetic factors associated with long-term courses and consequences of mood disorders in Korean patients.

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine.

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

Objective Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients. Methods Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D). Results The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group. Conclusion Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.