The Radiological Response Rate Pattern Is Associated With Recurrence Free Survival in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy / 한국유방암학회지

Purpose@#The aim of this study was to evaluate the radiological response rate patterns during neoadjuvant chemotherapy (NAC) in patients with breast cancer. @*Methods@#Patients who underwent NAC with two specific chemotherapy regimens (doxorubicin with cyclophosphamide or doxorubicin with docetaxel) and who underwent a response evaluation every two cycles were included in the study. The initial response ratio was defined as the ratio of the largest tumor diameter at diagnosis to that after two cycles of NAC. The latter response ratio was defined as the ratio between the tumor size after two cycles and that after four cycles of NAC. The radiological response rate pattern was divided into three groups: the fast-to-slow response group (F–S group, initial response ratio > latter response ratio + 20%), slow-to-fast response group (S–F group, latter response ratio > initial response ratio + 20%), and constant response group (less than 20% difference between the initial and latter response ratios). @*Results@#In total, 177 patients were included in the analysis. Forty-two (23.9%) patients were categorized into the F–S group, 26 (14.8%) into the S–F group, and 108 (61.2%) into the constant group. Clinicopathologic factors did not differ according to radiologic response rate patterns. The median follow-up period was 50 months (range, 3–112) months. In the univariate analysis, the F–S group had a significantly worse recurrence-free survival than the S–F and constant groups (hazard ratio [HR], 3.63; 95% confidence interval [CI], 1.05–12.46; p = 0.041). The F–S group also presented with significantly worse survival than the S–F group in the multivariate analysis (HR, 3.45; 95% CI, 1.00–11.89; p = 0.049). @*Conclusion@#The F–S group had a poorer survival rate than the S–F group. Radiological response rate patterns may be useful for accurate prognostic assessments, especially when considering post-neoadjuvant therapy.

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations / 한국유방암학회지

Purpose@#Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes;however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. @*Methods@#Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. @*Results@#Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. @*Conclusion@#As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2.A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations / 한국유방암학회지

Purpose@#Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes;however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. @*Methods@#Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. @*Results@#Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. @*Conclusion@#As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2.A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Liver transplantation in an adult patient with hepatocellular carcinoma following liver cirrhosis as a complication of the Fontan procedure -A case report-

Background@#Fontan-associated liver disease (FALD) is a hepatic disorder caused by hemodynamic changes and systemic venous congestion following the Fontan procedure. FALD includes liver cirrhosis and hepatocellular carcinoma (HCC), both of which may require liver transplantation (LT). However, the Fontan circulation, characterized by elevated central venous pressure and reduced cardiac output, is a challenging issue for surgeons and anesthesiologists.Case: We report a living-donor LT for the treatment of HCC. The patient was a 24-year-old male who underwent the Fontan procedure for pulmonary atresia and right ventricle hypoplasia. We focused on maintaining enough blood volume for cardiac output without causing pulmonary edema, as the patient is not well adapted to changes in volume. Owing to a multidisciplinary approach, the surgery was successfully performed without fatal adverse events. @*Conclusions@#To our knowledge, this is the first case of isolated LT in a recipient who became an adult after having undergone the Fontan procedure.

Adverse drug reactions

There are no drugs without the risk of potential adverse reactions. All pharmacologically active substances can cause adverse drug reactions (ADRs). This paper aims at introducing recent trends in pharmacosurveillance systems for ADRs, which can be broadly classified into type A and B reactions. Since type A reactions are associated with drug pharmacology, they are usually dose-dependent and predictable. Whereas, type B reactions occur in some susceptible individuals, regardless of the pharmacological action of drug. Drug hypersensitivity reactions are typical examples of type B reactions and are subclassified according to the underlying pathomechanism. Recent advancements in pharmacogenomics have enlightened the understanding of individual differences in drug efficacy and susceptibility to ADRs. Therefore, expectations for safe personalized medicines are higher than ever before. However, premarketing clinical trials are too small and too short to uncover rare but serious ADRs and detect long-standing ADRs. In the past, post-marketing surveillance systems mainly focused on passive ADR monitoring systems, based on spontaneous reports. Recently, the importance of active pharmacovigilance systems, which use big data, is growing with recent advancements in medical informatics. Thus, regarding ADRs, suspecting and detecting the causative drug using causality assessment based on data science may contribute to decrease suffering induced by ADRs.

Adverse drug reactions

There are no drugs without the risk of potential adverse reactions. All pharmacologically active substances can cause adverse drug reactions (ADRs). This paper aims at introducing recent trends in pharmacosurveillance systems for ADRs, which can be broadly classified into type A and B reactions. Since type A reactions are associated with drug pharmacology, they are usually dose-dependent and predictable. Whereas, type B reactions occur in some susceptible individuals, regardless of the pharmacological action of drug. Drug hypersensitivity reactions are typical examples of type B reactions and are subclassified according to the underlying pathomechanism. Recent advancements in pharmacogenomics have enlightened the understanding of individual differences in drug efficacy and susceptibility to ADRs. Therefore, expectations for safe personalized medicines are higher than ever before. However, premarketing clinical trials are too small and too short to uncover rare but serious ADRs and detect long-standing ADRs. In the past, post-marketing surveillance systems mainly focused on passive ADR monitoring systems, based on spontaneous reports. Recently, the importance of active pharmacovigilance systems, which use big data, is growing with recent advancements in medical informatics. Thus, regarding ADRs, suspecting and detecting the causative drug using causality assessment based on data science may contribute to decrease suffering induced by ADRs.

Laparoscopic surgery for left-sided colon cancer: Clinical and long-term oncologic outcomes

PURPOSE: Laparoscopic surgery for left-sided colon cancer is one of the most frequent procedures performed in laparoscopic colorectal surgery. In this study, we analyzed clinical and long-term oncological outcomes of left-sided colon cancer patients who underwent conventional laparoscopic surgery (CLS) and hand-assisted laparoscopic surgery (HALS).METHODS: A total of 172 CLS patients and 72 HALS patients for left-sided colon cancer from July 2001 to December 2011 were included in this study. The collected data included the clinical and oncological outcomes. We analyzed overall survival and disease-free survival by tumor, node, metastasis (TNM) stage.RESULTS: The mean age of the patients was 64 years, and male patients were predominant. The mean follow-up period was 58.1 months. The number of patients that belong in each TNM stage 0, I, II, III, and IV was as follows: 17 (7%), 47 (19.2%), 70 (28.7%), 80 (32.8%), and 30 (12.3%), respectively. Overall 5-year survival rate for TNM stage I, II, III, and IV was 87.1%, 82.8%, 82%, and 12%, respectively. Overall 5-year survival rate for CLS group and HALS group was 90.2% and 66.7%, 86.5% and 77%, 88.7% and 67.4%, and 18.9% and 0%, respectively. Disease-free 5-year survival rate for TNM stage I, II, and III was 97.7%, 90.7%, and 72.8%, respectively. Disease-free 5-year survival rate for CLS group and HALS group was 97.3% and 100%, 100% and 78.8%, and 81% and 55.1%, respectively.CONCLUSION: These data show the feasibility and safety of laparoscopic surgery for left-sided colon cancer in terms of long-term oncological outcomes.

The Change of Heart Rate Variability in Anxiety Disorder after Given Physical or Psychological Stress / 수면정신생리

OBJECTIVES: This study was designed to assess the change of heart rate variability (HRV) at resting, upright, and psychological stress in anxiety disorder patients. METHODS: HRV was measured at resting, upright, and psychological stress states in 60 anxiety disorder patients. We used visual analogue scale (VAS) score to assess tension and stress severity. Beck depression inventory (BDI) and state trait anxiety inventories I and II (STAI-I and II) were used to assess depression and anxiety severity. Differences between HRV indices were evaluated using paired t-tests. Gender difference analysis was accomplished with ANCOVA. RESULTS: SDNN (Standard deviation of normal RR intervals) and low frequency/high frequency (LF/HF) were significantly increased, while NN50, pNN50, and normalized HF (nHF) were significantly decreased in the upright position compared to resting state (p < 0.01). SDNN, root mean square of the differences of successive normal to normal intervals, and LF/HF were significantly increased, while nHF was significantly decreased in the psychological stress state compared to resting state (p < 0.01). SDNN, NN50, pNN50 were significantly lower in upright position compared to psychological stress and nVLF, nLF, nHF, and LF/HF showed no significant differences between them. CONCLUSION: The LF/HF ratio was significantly increased after both physical and psychological stress in anxiety disorder, but did not show a significant difference between these two stresses. Significant differences of SDNN, NN50, and pNN50 without any differences of nVLF, nLF, nHF, and LF/HF between two stresses might suggest that frequency domain analysis is more specific than time domain analysis.

Recent Updates on Acetaminophen Hepatotoxicity: The Role of Nrf2 in Hepatoprotection

Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

Expression and Characterization of alpha-Methylacyl CoA Racemase from Anisakis simplex Larvae

Larval excretory-secretory products of Anisakis simplex are known to cause allergic reactions in humans. A cDNA library of A. simplex 3rd-stage larvae (L3) was immunoscreened with polyclonal rabbit serum raised against A. simplex L3 excretory-secretory products to identify an antigen that elicits the immune response. One cDNA clone, designated as alpha-methylacyl CoA racemase (Amacr) contained a 1,412 bp cDNA transcript with a single open reading frame that encoded 418 amino acids. A. simplex Amacr showed a high degree of homology compared to Amacr orthologs from other species. Amacr mRNA was highly and constitutively expressed regardless of temperature (10-40degrees C) and time (24-48 hr). Immunohistochemical analysis revealed that Amacr was expressed mainly in the ventriculus of A. simplex larvae. The Amacr protein produced in large quantities from the ventriculus is probably responsible for many functions in the development and growth of A. simplex larvae.

Anisakis simplex Larvae: Infection Status in Marine Fish and Cephalopods Purchased from the Cooperative Fish Market in Busan, Korea

The infection status of marine fish and cephalopods with Anisakis simplex third stage larva (L3) was studied over a period of 1 year. A total of 2,537 specimens, which consisted of 40 species of fish and 3 species of cephalopods, were purchased from the Cooperative Fish Market in Busan, Korea, from August 2006 to July 2007. They were examined for A. simplex L3 from the whole body cavity, viscera, and muscles. A. simplex L3 were confirmed by light microscopy. The overall infection rate reached 34.3%, and average 17.1 larvae were parasitized per infected fish. Fish that recorded the highest infection rate was Lophiomus setigerus (100%), followed by Liparis tessellates (90%), Pleurogrammus azonus (90%), and Scomber japonicus (88.7%). The intensity of infection was the highest in Gadus macrocephalus (117.7 larvae per fish), followed by S. japonicus (103.9 larvae) and L. setigerus (54.2 larvae). Although abundance of A. simplex L3 was not seasonal in most of the fish species, 10 of the 16 selected species showed the highest abundance in February and April. A positive correlation between the intensity of L3 infection and the fish length was obvious in S. japonicus and G. macrocephalus. It was likely that A. simplex L3 are more frequently infected during the spring season in some species of fish. Our study revealed that eating raw or undercooked fish or cephalopods could still be a source of human infection with A. simplex L3 in Korea.