Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. @*Materials and Methods@#Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. @*Results@#A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. @*Conclusion@#We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Prognosis according to the timing of recurrence in breast cancer

Purpose@#Clinically, breast cancer can be divided into 4 subtypes based on the presence of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67. Because the pattern and time of recurrence vary according to the subtype, we evaluated whether there was a difference in overall survival (OS) among the subtypes according to the time and type of recurrence. @*Methods@#A total of 2,730 patients who underwent breast cancer surgery were analyzed. Early and late recurrence were defined as recurrence within and after 5 years of diagnosis, respectively. Recurrence type was categorized as locoregional recurrence or systemic recurrence. @*Results@#Hormone receptor-positive tumors were significantly more frequent in the late recurrence group than in the early recurrence group (estrogen receptor positive, 47.8% [early] vs. 78.7% [late]). However, there was no difference in the rate of HER2 overexpression (HER2+, 38.1% [early] vs.39.0% [late]). In subgroup analysis, early recurrence was a significant prognostic factor for OS in all subtypes. However, late recurrence was a significant prognostic factor for OS only in the luminal B subtype (hazard ratio of 4.30). In addition, the luminal B type had the highest proportion in late recurrence patients (63.2%). @*Conclusion@#The luminal B subtype had a high rate of late recurrence, and late recurrence was a poor prognostic factor for OS only in this subgroup. Therefore, further targeted treatments for luminal B breast cancer are needed and patients with this subtype require close long-term surveillance.

PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. @*Materials and Methods@#We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. @*Results@#Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. @*Conclusion@#Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Intraoperative Neuromonitoring during Thyroid Surgery

Intraoperative neuromonitoring is a well-established method used to prevent intraoperative nerve damage, and many studies have been performed in thyroid surgery. We introduced the basic concept and practical application of intraoperative neuromonitoring, as well as its standardized techniques and detailed contents. In addition, the contents of this still yet relatively unknown field, such as its application in transoral robotic thyroidectomy and its application to the external branches of the superior laryngeal nerve, were summarized by referring to many previous studies.

Intraoperative Neuromonitoring during Thyroid Surgery

Intraoperative neuromonitoring is a well-established method used to prevent intraoperative nerve damage, and many studies have been performed in thyroid surgery. We introduced the basic concept and practical application of intraoperative neuromonitoring, as well as its standardized techniques and detailed contents. In addition, the contents of this still yet relatively unknown field, such as its application in transoral robotic thyroidectomy and its application to the external branches of the superior laryngeal nerve, were summarized by referring to many previous studies.

Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. @*Materials and Methods@#The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. @*Results@#The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. @*Conclusion@#L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

Transoral Robotic Thyroidectomy: The Overview and Suggestions for Future Research in New Minimally Invasive Thyroid Surgery

PURPOSE OF REVIEW: This journal introduces a overview in depth about the evolution of transoral robotic thyroidectomy, which has been encountering major confrontations in expanding its indications. RECENT FINDINGS: Transoral robotic thyroidectomy (TORT) is one of the newest approaches and draws attention because of its cosmetic excellence. The major advantage of TORT is comparatively smaller flap dissection area than other remote-access methods. The other advantage of TORT is that the wounds of lips fades out over time, and leaves concealed scar near axilla. SUMMARY: TORT can be done safely to the appropriately selected patients by surgeon expertise in robotic thyroidectomy. It might be a potential alternative surgical approach for thyroidectomy to surgeons who are experienced in remote-access robotic surgery.

Neoadjuvant Chemotherapy and Prognosis of Pregnancy-Associated Breast Cancer: A Time-Trends Study of the Korean Breast Cancer Registry Database / 한국유방암학회지

PURPOSE: Pregnancy-associated breast cancer (PABC) is rare, and its cause and prognosis are not well known. Additionally, treatment is limited with respect to the risk to the fetus. The purpose of this study was to investigate the characteristics and treatment trends of PABC and the survival rate according to the treatment. METHODS: In the Korean Breast Cancer Society Registry database, women younger than 50 years and who were diagnosed with breast cancer from 1996 to 2015 were included. PABC was defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. RESULTS: We examined 411 patients with PABC and 83,381 patients with non-PABC. Over time, the proportions of patients undergoing breast-conserving surgery and sentinel lymph node biopsy increased, and neoadjuvant chemotherapy and radiation therapy administration rates also increased. In the past, the overall survival of patients with PABC was poorer than that of patients with non-PABC, but there was no difference in overall survival rates in more recent years. There was no difference in overall survival rates between patients who received neoadjuvant chemotherapy (hazard ratio [HR], 1.28; 95% confidence interval [CI], 0.66–2.49; p=0.459), but PABC conferred poorer prognosis than non-PABC in patients receiving adjuvant chemotherapy (HR, 1.63; 95% CI, 1.27–2.08; p < 0.001). CONCLUSION: There was no difference in the prognosis between patients with PABC and those with non-PABC receiving neoadjuvant chemotherapy. The increase in neoadjuvant chemotherapy according to current treatment guidelines is expected to improve the survival rate of patients with PABC.

Follow-up Outcomes of Benign Pathology Initially Assigned as Breast Imaging Reporting and Data System Category 4A and 3 / 한국유방암학회지

PURPOSE: This retrospective study investigated if the initially assigned category 4A or 3 in concordant benign lesions, after ultrasound (US)-guided core needle biopsy, could affect follow-up compliance. METHODS: Eight hundred thirty-eight concordant benign lesions, after core needle biopsy (674, initial category 4A group and 164, category 3 group) and follow-up US, were included in our study. If an immediate surgical excision—a surgical excision before the next follow-up—exists, those cases with pathologic reports were collected. Statistical comparisons for the result of follow-up US compliance, additional biopsy, and malignant rates among 6-month, 12-month, and long-term intervals were performed by using the chi-square test. The log-rank test was used to compare compliance rates in the timing of first follow-up between the two groups, with a significance level of 0.05. RESULTS: The number of immediate surgical excision was higher in the category 4A group (11.1%) than in the category 3 group (6.1%); only one cancer was found in the category 4A group. The patients' compliance rate in a 6-month follow-up showed an increase (p=0.003) in the category 4A group. The additional biopsy rate was higher in the initial category 4A group (10.9%) than in the category 3 group (1.9%) with statistical significance (p=0.001); four cancers were found on additional biopsy in the category 4 group. No cancer was detected in the initial category 3 group, both on immediate surgical excision and follow-up. CONCLUSION: The initial category 4A or 3 of the Breast Imaging Reporting and Data System could be a significant factor that affects immediate surgical excision and follow-up compliance. Cancers were detected only in the initial category 4A group of concordant benign lesions. More attention should be paid to the concordant benign lesions from the initial category 4A group than from the category 3 group.

Erratum: Follow-up Outcomes of Benign Pathology Initially Assigned as Breast Imaging Reporting and Data System Category 4A and 3 / 한국유방암학회지

This article was initially published on the Journal of Breast Cancer with a misspelled the Institutional Review Board (IRB) approval number. The IRB number should be corrected as “NCC2014-0031”.

Menopause and Cognitive Function : Hospitalized Female Patients with Depression

OBJECTIVES: Although forgetfulness is a common complaint among menopausal depressed women, there is still a debate about the relationship between memory impairment and menopause. The aim of this study is to examine whether menopause is related to cognitive decline among women with depressive disorders. We hypothesized that postmenopausal depressed women show generally poorer performance than premenopausal depressed women on various cognitive function tests. METHODS: With a retrospective chart review, we identified a total of 87 female patients (45 premenopausal patients and 42 postmenopausal patients) who were hospitalized with depressive disorders from 2000 to 2016. Demographic and clinical variables and cognitive test results were compared between two groups. RESULTS: ducation year is longer in premenopausal group than postmenopausal group whereas clinical characteristics (illness duration, recurrence, and symptom severity) and mean Intelligence Quotient (IQ) were similar between two groups. The postmenopausal group took longer time for Bender-Gestalt Test (BGT) recall, Trail Making Test (TMT)-A, and TMT-B than the premenopausal group. After controlling for age and education, significant difference was remained for BGT recall (p = 0.029). CONCLUSIONS: Postmenopausal state may be related with decline of visuospatial memory function, in particular, among depressed female patients. Other areas of cognitive function including complex attention, verbal memory, auditory memory, and working memory might be interpreted while considering age and education level.

Primary Squamous Cell Carcinoma of the Remnant Stomach after Subtotal Gastrectomy

Primary squamous cell carcinoma (SCC) of the stomach is a very rare disease. However, the pathogenesis, clinical characteristics, and prognosis of gastric SCC are controversial and remain to be elucidated. Herein, we report a case of primary gastric SCC of the remnant stomach after subtotal gastrectomy. A 65-year-old man was admitted to our hospital due to epigastric discomfort and dizziness. He had undergone subtotal gastrectomy 40 years previously for gastric ulcer perforation. Endoscopy revealed a normal esophagus and a large mass in the remnant stomach. Abdominal computed tomography revealed enhanced wall thickening of the anastomotic site and suspected metachronous gastric cancer. Endoscopic biopsy revealed SCC. Total gastrectomy was performed with Roux-en-Y esophagojejunostomy. A 10-cm tumor was located at the remnant stomach just proximal to the previous area of anastomosis. Pathologic examination showed well-differentiated SCC extended into the subserosa without lymph node involvement (T3N0M0). The patient received adjuvant systemic chemotherapy with 6 cycles of 5-FU and cisplatin regimen, and he is still alive at the 54-month follow-up. According to the treatment principles of gastric cancer, early detection and radical surgical resection can improve the prognosis.

Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications. MATERIALS AND METHODS: We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed. RESULTS: Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2- tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2- tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2- throughout. The HR+/HER2- to TN group had significantly poorer recurrence-free survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2-showed improved comparable survival outcomes. CONCLUSION: Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.

SAPHO Syndrome in a Patient with Breast Cancer Mimicking Bone Metastasis: A Case Report

A 66-year-old woman was transferred to our hospital due to her right breast cancer. Preoperative breast MRI shows 1.9 cm malignancy on her right breast (cT1N0M0) and incidentally found osteosclerotic change of left coststernoclavicular region. Bone scintigraphy showed hot uptake and the possibility of bone metastasis was not excluded. However, because the bone metastasis is not common in early stage cancer and the costosternoclavicular region is not common site, other possibility should be considered. SAPHO syndrome can be diagnosed even in the absence of dermatosis when there is an axial or appendicular osteitis and hyperostosis, especially in costosternoclavicular region. Though breast imaging specialists are not accustomed to this disease entity, awareness and diagnosis of the SAPHO syndrome can help differentiate bone metastasis.

Analysis of the occupational stress of Korean surgeons: a pilot study / 대한외과학회지

PURPOSE: Surgeons serve one of the most challenging and stressful professions. Ineffective control of occupational stress leads to burnout of the surgeon. The aim of this study was to obtain preliminary data on the sources and the degree of stress of surgeons and to determine the feasibility of the survey. METHODS: A total of 63 surgeons in our three affiliated hospitals were enrolled in this study. Fifty-five questions were used to assess the demographics, characteristics and Korean occupational stress scale (KOSS), which were prepared and validated by the National Study for Development and Standardization of Occupational Stress. RESULTS: Forty-seven of the 63 surgeons participated in this study (74.6%). The mean KOSS score of the survey was 50.9 +/- 8.55, which was significantly higher than that of other professions (P < 0.01). Drinking and smoking habits were not related to the KOSS score. Doing exercise was related to a low KOSS score in terms of low KOSS total score (P < 0.01). Average duty hours (P < 0.01) and night duty days per week (P = 0.01) were strongly related to higher KOSS in the linear regression analysis. CONCLUSION: This is the first study to evaluate job stress of surgeons in Korea. This study showed that Korean Surgeons had higher occupational stress than other Korean professions. A larger study based on this pilot study will help generate objective data for occupational stress of Korean Surgeons by performing a survey of the members of the Korean Surgical Society.

The Efficacy of Discharge Instructions Provided by a Tablet Personal Computer for Aiding the Comprehension and Satisfaction of Patients with Ureteral Stones

PURPOSE: This study was conducted in order to evaluate the possibility of improving the comprehension and satisfaction of patients discharged after receiving discharge instructions using a tablet personal computer (tablet PC), compared with conventional discharge instructions. METHODS: A randomized, prospective, consecutive, exploratory study was conducted on patients with ureteral stones in an emergency department (ED). The patients' objective comprehension, satisfaction, and subjective comprehension regarding their discharge instructions were compared with regard to discharge instruction (traditional verbal method, N=53 versus tablet PC method, N=53). RESULTS: No statistically significant differences in age, gender, or level of education were observed between the two groups. The mean number of correct answers regarding ureteral stones on the questionnaire was 2.35+/-1.02 in the conventional group (CG) and 3.37+/-0.9 in the tablet PC group (TG) (p0.05). The subjective comprehension score was 7.42 in the CG and 7.8 in the TG (p>0.05). CONCLUSION: Objective comprehension of ureteral stones showed improvement in the group with discharge instructions provided by the tablet PC. However, satisfaction and subjective comprehension did not show improvement.

Multicenter Survey of Intoxication Cases in Korean Emergency Departments: 2nd Annual Report, 2009

PURPOSE: The purpose of this study was to examine the occurrence of toxic exposure cases in Korean emergency centers using a toxic exposure surveillance system-based report form and to provide guidelines for the prevention and treatment of toxic exposures. METHODS: We retrospectively reviewed the medical records of toxic exposure patients who had visited emergency centers from January 2009 to December 2009. Epidemiology data points for the toxic exposure cases included age, gender, type of exposure, number and kind of substances involved, reason and route of poison exposure, management of the patients in the emergency departments, and the clinical outcome. RESULTS: A total of 3,501 patients from 12 emergency departments were enrolled in the study. 50.0% of the total exposure patients were male and 63.0% of the total cases were fatal. Acute intoxication occurred in 91.3% of the total patients and suicidal intent was the most common (43.3%) reason for exposure. The most common route of exposure was ingestion (75.9%). Of the total cases, pesticides were involved in 26.3%, sedatives/hypnotics/antipsychotics were involved in 22.0%, and bites and envenomations were involved in 15.7%. CONCLUSION: We provided a database of patients who were admitted to emergency departments after poisoning incidents. We recommend that toxicology professionals develop a classification scheme for toxicants which is adequate for Korean domestic circumstances and initiate a toxic surveillance system for all types of exposures. With support of a psychiatric surveillance system for suicidal patients and establishment of social mediation for pesticide poisoning, major reductions in poison exposures can be achieved.

Toxicologic Review of the Dietary Supplements Glucosamine and Chitosan

Recently, westernized diet and lifestyles have led to obesity and various adult diseases resulting in a negative influence on the quality of life. There has been an increased interest in choosing proper diet and regular exercise in order to lead a healthy life. The number of people looking for dietary supplements has increased steadily. Dietary supplements are products intended to help maintain or improve the health of consumers. However, if customers take dietary supplements excessively, they may be harmful due to side effects, misuse, abuse and overdose. I performed a toxicologic review of the dietary supplements, glucosamine and chitosan, which are widely used in the country in order to provide the proper understanding of safety of these products.

Does Switching Rescuers Every 2 Minutes Improve the Quality of Chest Compression Provided in Cardiopulmonary Resuscitation?

PURPOSE: Effective chest compressions may improve the return of spontaneous circulation and positive neurologic outcomes in cardiac arrest victims. Out of concern for rescuer fatigue, guidelines for cardiopulmonary resuscitation (CPR) recommend that the individual applying chest compressions should be switched every 2 minutes, but there is little evidence to support this recommendation. In this study, we investigated whether or not changing the individual who is applying chest compressions every 2 minutes during cardiopulmonary resuscitation is appropriate or not. METHODS: We recruited health personnel working at one university hospital on a volunteer basis. On a randomly assigned day, we compared the effectiveness of the use of multiple rescuers following the 2 minute guideline, versus single rescuer (rescuer-limited) in performance of CPR. The resulting data was collected by use of CPR recording technology, and chest compression quality variables including compression rate, compression depth, proportion of adequate compression depth, and proportion of incomplete recoil were recorded. RESULTS: There were statistically significant improvements in the rescuer-limited trial outcome including average compression depth (p=0.013), proportion of adequate compression depth (p=0.027), and difference in reported fatigue (0.007). CONCLUSION: In this study, we found that a rescuer-limited method is more effective than the multiple rescuer method in terms of subjective fatigue and chest compression quality metrics.

Methylene Blue

Methylene blue is a very effective reducer of drug-induced methemoglobinemia. It has dose-dependent oxidation or reduction properties. In most cases, a dose of 1 to 2 mg/kg IV given over 5 minutes and immediately followed by a 15- to 30-mL fluid flush to minimize the local pain is both effective and relatively safe. The onset of action is quite rapid, and the effects are usually seen within 30 minutes. The dose may be repeated after 30 to 60 minutes and then every 2 to 4 hours as needed. The total dose should not exceed 7 mg/kg as a single dose or 15 mg/kg within 24 hours. Repeated treatment may be needed for treating compounds that have prolonged elimination or those compounds that undergo enterohepatic recirculation (e.g., dapsone). Methylene blue can cause dose-related toxicity. At high doses, methylene blue can also induce an acute hemolytic anemia and rebound methemoglobinemia. The reasons for treatment failure with methylene blue include ineffective GI decontamination, the existence of other forms of hemoglobin (e.g., sulfhemoglobin), a low or high dose of methylene blue and the toxicokinetics of some agents, such as aniline, benzocaine or dapsone.