Purpose: There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. Materials and Methods: Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. Results: 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. Conclusion Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Objectives: Treatment guidelines or an algorithm can help clinicians implement better practices and clinical decisions. Therefore, the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) was revised again through a consensus of expert opinion. The diagnosis and treatment of mixed features are not simple, and there are many things to discuss. We describe the preferences and recommendations from KMAP-BP 2022 for the treatment of mood episodes with mixed features. Methods: We revised the KMAP-BP 2018 questionnaire and conducted the survey with expert clinicians. Out of ninety-three members of the review committee, eighty-seven completed the survey. We analyzed the answers, discussed the data, and held a clinician hearing. Results: In first-step strategies for mixed features with more manic symptoms, a combination of a mood stabilizer and an atypical antipsychotic is the treatment of choice. Mood stabilizer monotherapy and atypical antipsychotic monotherapy are preferred strategies. For mixed features with more depressive symptoms, a combination of mood stabilizer and atypical antipsychotic, a combination of atypical antipsychotic and lamotrigine (LMT), atypical antipsychotic monotherapy, a combination of mood stabilizer and LMT, and mood stabilizer monotherapy are preferred. For mixed features with similar manic symptoms and depressive symptoms, a combination of mood stabilizer and atypical antipsychotic, atypical antipsychotic monotherapy, and mood stabilizer monotherapy are preferred. Conclusion For mixed features, a combination of mood stabilizer and atypical antipsychotic is generally preferred, and LMT is preferred for depressive symptoms. Compared with KMAP-BP 2018, more diverse strategies and drugs are being attempted for the treatment of mixed features.

Objectives: After the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002, its fifth revision was completed in 2022 to reflect the recent rapid developments and research into bipolar disorder and its psychopharmacology. Methods: According to the methodology for previous versions, the depressive episode section of KMAP-BP 2022 was revised based on a survey consisting of 11 questions. Among ninetythree experts, eighty-seven members of the review committee (93.5%) completed the survey.The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence. Results: Overall, the results from this study showed little change in comparison with previous versions of KMAP-BP. However, there have been significant changes in recommendations over the span of about 20 years. The preferences for lamotrigine and atypical antipsychotics, especially aripiprazole, quetiapine, and olanzapine, have shown a tendency to continuously increase, but the preferences for risperidone and ziprasidone have not increased, but have decreased. Moreover, the preference for typical antipsychotics has significantly decreased. Additionally, concerns over the use of antidepressants in bipolar depression have been raised, and their use is not recommended in KMAP-BP 2022 as a first-line treatment. Conclusion Pharmacotherapy for acute depressive episodes with various clinical progressions and various subtypes still shows diversity, compared to pharmacotherapy for mania. We look forward to the development of bipolar depressive, episode-specific therapeutic drugs in the future, and hope the fifth update of KMAP-BP will be a complementary option for clinicians and their patients with bipolar disorder.

Objectives: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is a consensus-based medication guideline. To reflect advances in pharmacotherapy for bipolar disorders, we updated KMAP-BP to provide more timely information for clinicians. Methods: We conducted a survey using a questionnaire on treatments formanic/hypomanic episodes. Eighty-seven members among ninety-three members of the review committee (93.5%) completed the survey. Each treatment strategy or treatment option for manic/hypomanic episodes was evaluated with an overall score of 9, and the resulting 95% confidence interval treatment options were categorized into three recommendation levels (primary, secondary, and tertiary). The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence. Results: The combination of a mood stabilizer and an atypical antipsychotic, monotherapy with a mood stabilizer, or monotherapy with an atypical antipsychotic were recommended as the firstline pharmacotherapeutic strategy for the initial treatment of mania without psychotic features. The mood stabilizer and atypical antipsychotic combination was the treatment of choice, and atypical antipsychotic monotherapy was the first-line treatment for mania with psychotic features. When initial treatment fails, a combination of mood stabilizer+atypical antipsychotic and switching to another first-line agent is recommended. For hypomania, monotherapy with either mood stabilizer or atypical antipsychotic is the recommended first-line treatment, but the mood stabilizer+atypical antipsychotic combination is recommended as well. Conclusion It is notable that there were changes in the preferences for the use of individual atypical antipsychotics, and the preference for the use of mood stabilizer increased for treatment-resistant mania.

Objectives: The pharmacotherapy of bipolar disorder is complex. A treatment guideline or algorithm can help clinicians implement better practices and clinical decisions. Therefore, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was revised through expert consensus on pharmacotherapy for bipolar disorder. Methods: We revised the KMAP-BP 2018 questionnaire and conducted a survey of expert clinicians. Out of ninety-three members of the review committee, eighty-seven completed the survey. We analyzed the answers, discussed the data, and held a clinician hearing. Here, we report the results from KMAP-BP 2022. Results: The preferred first-step strategies for acute euphoric mania are a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. For psychotic mania, an MS and AAP combination, and AAP monotherapy are preferred. For hypomania, MS monotherapy and AAP monotherapy are preferred. The first-step strategies for mild to moderate bipolar depression are MS monotherapy, lamotrigine (LMT) monotherapy, AAP monotherapy, an MS+AAP combination, and an AAP+LMT combination. For non-psychotic severe depression, the MS+AAP combination, the AAP+LMT combination, and the MS+LMT combination are preferred. For psychotic severe depression, MS+AAP and AAP+LMT are preferred. Conclusion We obtained expert consensus and developed KMAP-BP 2022. Compared with KMAP-BP 2018, we can figure out clinicians’ preferences and decisions in real clinical situations more clearly. The preference for AAP increased, and that of MS and an antidepressant decreased. We hope KMAP-BP 2022 is helpful for clinicians who treat patients with bipolar disorder.

Objective: We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder. Methods: The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts. Results: For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state. Conclusion The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Objectives: This study revised the Korean Medication Algorithm Project for Bipolar Disorder 2018 for rapid cycling. Methods: Questionnaires to survey the expert opinion of medication for rapid cycling were completed by a review committee consisting of 87 Korean expert psychiatrists. The experts’ opinions were classified into three categories based on the lowest category in which the confidence interval fell (6.5≤ for first-line, 3.5≤ for second-line, and 3.5> for third-line treatment). Results: The first-line treatments were a combination of mood stabilizers and atypical antipsychotics, atypical antipsychotics monotherapy, or mood stabilizer monotherapy. Furthermore, a mood stabilizer with lamotrigine therapy and an atypical antipsychotic with lamotrigine combinations was the first-line treatment for a depressive episode. The first-line medications in all episodes were valproate, lithium, quetiapine, olanzapine, and aripiprazole. Risperidone was the first-line medication in manic episodes and mixed states, and lamotrigine was the first-line medication for treating depressive episodes. Conclusion Compared to the surveys in 2018, the preference for atypical antipsychotics and lamotrigine has increased, and the modalities as a second-line treatment are more diversified.

Objectives: The objective of this study was to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) 2022: children and adolescents. Methods: We performed a survey, using a questionnaire comprising 23 questions according to various situations facing children and adolescents with bipolar disorders. A total of 40 of the 60 experts in child and adolescent psychiatry responded to the survey. Results: The first-line pharmacotherapeutic strategies for manic and depressive episodes in children with bipolar disorders were a combination of mood stabilizer (MS) and atypical antipsychotics (AAP). The first-line medications selected for these children were aripiprazole (treatment of choice, TOC) and risperidone. The first-line pharmacotherapeutic strategies for manic episodes in adolescents were a combination of MS and an AAP (TOC), monotherapy with MS, and monotherapy with an AAP. Lithium, valproate, aripiprazole, risperidone, and quetiapine were selected as first-line medications for these adolescents. First-line pharmacotherapeutic strategies for depressive episodes in adolescents were a combination of MS and an AAP, monotherapy with MS, and monotherapy with an AAP. The first-line pharmacotherapeutic strategies for the depressive episodes in adolescents at high risk for bipolar disorder were a combination of MS and AAP and monotherapy with an AAP. Lithium, valproate, aripiprazole (TOC), quetiapine, and risperidone were selected as first-line medications for the treatment of depressive episodes in adolescents with bipolar disorder. Conclusion It is expected that the present KMAP-BP 2022: children and adolescents will give the direction and be usefully applied by clinicians to treat children and adolescents with bipolar disorders.