Factors That Influence Attitudes toward Advance Directives among Female Cancer Patients / 한국호스피스완화의료학회지

Purpose@#This study aimed to identify attitudes toward advance directives (ADs) among female cancer patients and factors related to ADs. @*Methods@#The study was conducted at a university hospital in Seoul from September 19, 2020, to January 20, 2021. The participants were 153 patients diagnosed with gynecological cancer or breast cancer. Data were collected using questionnaires and included general characteristics, disease- and AD-related characteristics, knowledge and attitudes about ADs, and attitudes about dignified death.Data were analyzed using the t-test, analysis of variance, and multiple regression analysis. @*Results@#Only 2% of the participants completed ADs. The mean score for attitudes toward ADs was 3.30, indicating a positive knowledge and attitude toward dignified death. Thefactors related to attitudes toward ADs were attitudes toward dignified death (β=0.25, P=0.001), experience discussing life-sustaining treatment (β=0.17, P=0.037), preferred time to have a consultation about ADs (β=0.19, P=0.046), intention to write ADs (β= 0.15, P=0.038), and Eastern Cooperative Oncology Group Performance Status (β=-0.37, P＜0.001). The explanatory power of these variables for attitudes toward ADs was 38.5%. @*Conclusion@#Overall, patients preferred to have a consultation about ADs when they were still active, mentally healthy, and able to make decisions. Education about ADs should be provided to patients on the first day of hospitalization for chemotherapy or while awaiting treatment in an outpatient setting so patients can write ADs and discuss them with family and friends.

Perceived Social Support of Family Caregivers for People with Dementia:Concept Analysis

Purpose@#Most of the currently used concepts and measurements of social support have been relevant for general population. The main purpose of this study is to conduct the concept analysis of perceived social support(PSS) of family caregivers for people with dementia. @*Methods@#This study adopted the Walker and Avant concept analysis methodology. @*Results@#Findings from this concept analysis suggested four defining attributes of PSS of family caregivers for people with dementia: 1) PSS is help or assistance that family caregivers perceive as available when needed; 2) PSS is offered through socio-ecological structure; 3) PSS has a specific function to meet the needs of family caregivers; and 4) PSS includes quality aspects where family caregivers choose, use, or evaluate it. Borrowing from the socio-ecological model, this study proposed the structural aspects of PSS. This study also identified functional aspects of PSS, such as emotional support, informational support, appraisal support, and practical support. Finally, this study assessed quality aspects of PSS, such as satisfaction, timeliness, usefulness, accessibility, and coordination. @*Conclusion@#Focusing on family caregivers for people with dementia, we proposed a new model of PSS. The present study helped refine and clarify the concept of PSS of family caregivers for people with dementia. The results of this study may also contribute to promoting the development of more effective instruments for the concept.

Subcutaneous Panniculitis-Like T-Cell Lymphoma with Hemophagocytic Syndrome in a Child: A Successful Treatment with the BFM-NHL-90 Protocol / 임상소아혈액종양

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a distinct cutaneous lymphoma subtype that is characterized by pleomorphic T-cell infiltration of the subcutaneous tissue. SPTCL is usually associated with indolent clinical course. However, it can be complicated by hemophagocytic syndrome (HPS), which leads to worse prognosis. Childhood SPTCL is rare and there is no standardized treatment regimen of SPTCL with HPS. Here we report a pediatric case of SPTCL with HPS who responded favorably with multi-agent chemotherapy of the BFM (Berlin‐Frankfurt‐Münster)-NHL (non-Hodgkin lymphoma)-90 protocol.

Mutations of the Epidermal Growth Factor Receptor Gene in Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: Epidermal growth factor receptor (EGFR) is considered a potential therapeutic target for anti-EGFR therapy in triple-negative breast cancer (TNBC). However, the frequency of EGFR gene mutation in TNBC is low and varies with ethnicity. This study aimed to investigate the incidence of EGFR gene mutation in TNBC. METHODS: EGFR protein expression was evaluated by immunohistochemistry in tissue microarrays of 493 TNBC cases using four different primary antibodies, which included mutation-specific antibodies. For cases with an immunoreactivity level ≥1+, we performed pyrosequencing analysis for EGFR gene mutation. A case was considered mutation-positive when its mutation frequency minus its limit of detection (LOD) was >10%. Cases with mutation frequency higher than LOD were assessed for EGFR gene mutation status using the Cobas assay and by peptide nucleic acid-mediated polymerase chain reaction (PNA-clamping). RESULTS: Among 493 TNBCs, 148 (30.0%) exhibited staining ≥1+ for EGFR, including 78 with 1+, 49 with 2+, and 21 with 3+. Positive EGFR expression (≥2+) was significantly associated with lymphovascular invasion (p=0.010), but not with overall survival (p=0.444) or disease-free survival (p=0.388). None of the 493 TNBCs harbored an EGFR gene mutation. Among 148 cases with an EGFR staining result ≥1+, five (3.4%) showed mutation frequencies (4.4%–10.9%) higher than LOD (2.6%–4.3%) in exons 19 (L747_P753>Q) or 21 (L858R and L861Q) as determined by pyrosequencing. However, Cobas and PNA-clamping failed to detect the presence of EGFR gene mutation in these five cases. CONCLUSION: No activating mutation of EGFR gene of clinical significance was observed in 148 TNBC cases using three commercially available methods. Thus, EGFR gene mutation appears to be an extremely rare event in patients with TNBC.

Neuronal Differentiation of a Human Induced Pluripotent Stem Cell Line (FS-1) Derived from Newborn Foreskin Fibroblasts

Isolation of induced pluripotent stem cells (iPSCs) from fully differentiated somatic cells has revolutionized existing concepts of cell differentiation and stem cells. Importantly, iPSCs generated from somatic cells of patients can be used to model different types of human diseases. They may also serve as autologous cell sources that can be used in transplantation therapy. In this study, we investigated the neuronal properties of an iPSC line that is derived from human neonatal foreskin fibroblasts (FS-1). We initially examined the morphology and marker expression of FS-1 cells at undifferentiated stage. We then spontaneously differentiated FS-1 cells in suspension culture and examined the expression of markers representing three germ layers. We finally differentiated FS-1 cells into neuronal lineages by co-culturing them with PA6 stromal cells, and found that, under the conditions we used, they have a tendency to differentiate into more forebrain-type neurons, suggesting that FS-1 iPSC-derived neural cells will be useful to be used in cell therapy of stroke or Huntington's disease, among others. Taken together, FS-1 cells derived from human neonatal fibroblasts exhibit very similar properties with human ES cells, and can provide useful sources for cell therapy and various other applications.

Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status / 한국유방암학회지

PURPOSE: This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer. METHODS: We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status. RESULTS: Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2. CONCLUSION: CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.

Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status / 한국유방암학회지

PURPOSE: This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer. METHODS: We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status. RESULTS: Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2. CONCLUSION: CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach: A Case Report

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described mesenchymal tumor of the stomach. We report the first case of PAMT in Korea. A 52-yr-old man underwent esophagogastroduodenoscopy due to dyspepsia for 2 yr. There was a submucosal mass with small mucosal ulceration in the gastric antrum. The tumor measured 3.5 x 2.3 cm in size and showed multinodular plexiform growth pattern of bland-looking spindle cells separated by an abundant myxoid or fibromyxoid matrix rich in small thin-walled blood vessels. The tumor cells were negative for CD117 (c-KIT), CD34 and S-100 protein, but diffusely positive for smooth muscle actin consistent with predominant myofibroblastic differentiation. The patient is doing well without recurrence or metastasis for 5 months after surgery. Although there have been limited follow-up data, PAMT is regarded as a benign gastric neoplasm with histological and immunohistochemical charateristics distinguished from gastrointestinal stromal tumor and other mesenchymal tumors of the stomach.

HER2-Positive Breast Carcinomas with Co-amplification or Gain of Chromosome 17 Centromere Locus: Report of Three Cases and an Impact on HER2 Testing

Recently we experienced three cases of human epidermal growth factor receptor 2 (HER2)-amplified invasive breast carcinomas associated with co-amplification or gain of chromosome 17 centromere (CEP17) in silver-enhanced in situ hybridization (SISH) analysis. These cases revealed 2+ or 3+ staining for HER2 immunohistochemistry and >6 HER2 copies per cell on SISH analyses. However, the calculated HER2/CEP17 ratios were low (6 per cell vs HER2/CEP17 ratio>2.2). We recommend reporting raw SISH or fluorescence in situ hybridization data, including number of cells counted, average numbers of HER2 and CEP17 signals, and the calculated HER2/CEP17 ratio to prevent underreporting of HER2 amplification.

HER2 Status in Gastric Adenocarcinomas Assessed by Immunohistochemistry, Automated Silver-Enhanced In Situ Hybridization and Fluorescence In Situ Hybridization

BACKGROUND: Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas. METHODS: Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2. RESULTS: IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%. CONCLUSIONS: HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas. Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas.

Usefulness of DOG1 Expression in the Diagnosis of Gastrointestinal Stromal Tumors

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Expression of KIT protein (CD117) is an important diagnostic criterion of GIST. However, about 5% of GISTs are CD117 negative. Discovered on GIST 1 (DOG1) was introduced recently as a promising marker for GIST. We tested this new antibody in 105 GISTs tissue specimens, including 6 cases of metastatic GISTs, to determine the usefulness of DOG1 expression in the diagnosis of GISTs. METHODS: We performed immunohistochemical (IHC) staining for DOG1 and CD117 on tissue microarrays that included 70 gastric GISTs, 29 small intestinal GISTs, 6 metastatic GISTs, 14 gastric leiomyomas and 16 gastric schwannomas. RESULTS: DOG1 was positive in 98.1% (103/105) of GISTs and CD117 was positive in 97.1% (102/105) of GISTs. Only 1 case was negative for both markers. Two (66.7%) out of 3 GISTs tested CD117 negative were tested DOG1 positive. All leiomyomas and schwannomas were negative for both DOG1 and CD117. CONCLUSIONS: DOG1 was highly expressed in GIST including CD117 negative cases. Adding DOG1 testing to the IHC panel for diagnosing GIST will help to identify GIST patients who are CD117 negative but may otherwise benefit from targeted therapy.

Gastric Adenocarcinoma with Coexistent Hepatoid Adenocarcinoma and Neuroendocrine Carcinoma: A Case Report

This report represents a very rare case of a gastric adenocarcinoma that was coexistent with hepatoid adenocarcinoma and neuroendocrine carcinoma. A 77-year-old man was admitted to our hospital due to a huge ulcerofungating mass identified at the proximal body of the stomach. After a pathological diagnosis of the tumor as a poorly differentiated adenocarcinoma was made, the patient underwent a total gastrectomy with lymph node dissection. Microscopically, the tumor consisted of three morphologically distinct components-tubular adenocarcinoma, hepatoid adenocarcinoma and neuroendocrine carcinoma. The hepatoid adenocarcinoma component resembled a hepatocellular carcinoma and produced alpha-fetoprotein. The neuroendocrine carcinoma component was positive for chromogranin and synaptophysin immunostains. This is an example of the diverse morphological and immunophenotypical differentiation of gastric carcinomas.

The Usefulness and Limitations of Intraoperative Frozen Section Analysis of Sentinel Lymph Nodes in Patients with Breast Cancer / 한국유방암학회지

PURPOSE: Intraoperative frozen sectioning (FS) of sentinel lymph nodes (SLNs) is widely used to determine whether total axillary lymph node dissection should be performed in patients with breast cancer. We evaluated the usefulness and limitations of the FS protocol, which has been used in our institution for the intraoperative SLN examination. METHODS: We analyzed the FS results of SLNs in 807 invasive breast carcinoma patients who underwent intraoperative SLN biopsy between January 2005 and December 2007. Lymph nodes larger than 5 mm were sliced at 2 mm intervals and all the slices were submitted for FS. The remaining tissue of the SLN was formalin-fixed and paraffin-embedded for permanent sectioning (PS). If the FS result was negative for tumor cells, then immunohistochemical stain for pancytokeratin was performed. The metastatic SLNs were graded according to the AJCC cancer staging manual (6th edition). The results of FS and PS were compared with regard to the pathologic diagnosis. RESULTS: The average number of SLNs was 2.9 per patients. A total of 204 (25.3%) patients were reported to have a metastatic SLN(s) on the FS. Among the 603 patients with negative FS results, 34 (5.6%) patients showed metastasis on the PS. Another 10 (1.7%) patients who had negative results on FS showed isolated tumor cells on the PS or on the cytokeratin immunohistochemistry. Twenty-nine of the 34 (85.3%) false negative cases showed micrometastasis on the PS. Ten (29.4%) false negative results were caused by interpretation errors and 24 (70.6%) were caused by technical problems. CONCLUSION: The false negative rate of our protocol for FS of a SLN was low. The failure of FS was largely caused by the failure to detect micrometastasis. FS is a reliable method for an intraoperative SLN examination if a very stringent protocol is used.

Epithelial-myoepithelial Carcinoma Arising in the Nasal Cavity-Immunohistochemical and Electron Microscopic Study / 대한이비인후과학회지

Epithelial-myoepithelial carcinoma is a very rare malignant tumor accounting for less than one percent of sa1ivary gland neoplasms. Histologically, the tumor consists of a mixture of trabecular structure with double-layered arrangement of inner ductal cells and outer myoepithelial cells. Immunohistochemistry and electron microscopy confirm dual differentiation toward myoepithelial and ductal cells. We report a 22-year-old man with epithelial-myoepithelial carcinoma arising from nasal cavity, one of the most unusual locations.

A Case of Nonvenereal Sclerosing Lymphangitis of the Penis

The patient was a 41-year-old healthy man, who developed a tender, cord-like serpiginous mass just proximal to the coronal sulcus for two weeks. He was a sexually active, non-promiscuous, married man. We had taken a biopsy, and noticed the subsiding of the lesion without further treatment. Nonvenereal sclerosing lymphangitis of the penis is a rare self-limiting peculiar disorder involving the lymphatics of the penile sulcus. Clinically, it presents as a cord-like nodular penile lesion with characteristic cartilaginous firmness. Histologically, it is described as hypertrophy and sclerosis of the lymphatic vessel walls with mild inflammatory cellular infiltration, and occasional obstruction of the lymphatic vessel. But, because such features including sclerosis varies according to the time when the biopsy was taken, they are not attributable to all cases. Our case shows the same clinical and pathological features of ‘benign transient lymphangiectasis’. Except for the painful cases, no specific treatments are usually warranted.