NOTCH1 Pathway is Involved in Polyhexamethylene Guanidine-Induced Humidifier Disinfectant Lung Injuries

0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.

The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma In Situ / 한국유방암학회지

Purpose@#Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. @*Methods@#RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. @*Results@#Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. @*Conclusion@#Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.

The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma In Situ / 한국유방암학회지

Purpose@#Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. @*Methods@#RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. @*Results@#Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. @*Conclusion@#Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.

Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Extranodal extension (ENE) is closely associated with the aggressiveness of both colon and rectal cancer. This study evaluated the clinicopathologic significance and prognostic impact of ENE in separate populations of patients with colon and rectal cancers. MATERIALS AND METHODS: The medical records of 2,346 patients with colorectal cancer (CRC) who underwent curative surgery at our institution between January 2003 and December 2011 were clinically and histologically reviewed. RESULTS: ENE was associated with younger age, advanced tumor stage, lymphovascular invasion (LVI), and perineural invasion (PNI) in both colon and rectal cancer. ENE rates differed significantly in patients with right colon (36.9%), left colon (42.6%), and rectal (48.7%) cancers (right vs. left, p=0.037; left vs. rectum, p=0.009). The 5-year disease-free survival (DFS) rate according to ENE status and primary tumor site differed significantly in patients with ENE-negative colon cancer (80.5%), ENE-negative rectal cancer (77.4%), ENE-positive colon cancer (68.6%), and ENE-positive rectal cancer (64.2%) (p<0.001). Multivariate analysis showed that advanced tumor stage, ENE, LVI, PNI, and absence of adjuvant chemotherapy were independently prognostic of reduced DFS in colon and rectal cancer patients. CONCLUSION: ENE is closely associated with the aggressiveness of colon and rectal cancers, with its frequency increasing from the right colon to the left colon to the rectum. ENE status is a significant independent predictor of DFS in CRC patients irrespective of tumor location. ENE might be more related with distally located CRC.

Androgen receptor as a prognostic biomarker and therapeutic target in uterine leiomyosarcoma / 부인종양

OBJECTIVE: To investigate the expression of androgen receptor (AR) and its correlation with disease status and survival outcome in uterine leiomyosarcoma with other hormone receptors. METHODS: The medical records and paraffin blocks of 42 patients were reviewed. The immunohistochemical expression of AR, estrogen receptor (ER), progesterone receptor (PR), gonadotropin releasing hormone (GnRH), and cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) were assessed using tissue microarray. RESULTS: In total, AR expression was observed in 11 patients (26.2%). International Federation of Gynecology and Obstetrics (FIGO) stage and AR were independent factors for disease-free survival (DFS) in multivariate regression analysis (odds ratio [OR]=5.8; 95% confidence interval [CI]=1.2–28.4 and OR=0.2; 95% CI=0.05–0.90; p=0.029 and 0.032, respectively). There were no deaths in the AR expression group, whereas the 5-year overall survival (OS) was 54.8% in the no expression group (p=0.014). Co-expression of ER and/or PR with AR was associated with significantly better 5-year DFS and OS than those with negative AR (72.7% vs. 28.6% and 100% vs. 64.3%; p=0.020 and 0.036, respectively). AR may be an independent prognostic marker regardless of ER/PR. CONCLUSION: AR can be a potential prognostic biomarker in uterine leiomyosarcoma.

Gastric Cancer Caused by Adenoma: Predictive Factors Associated with Lesions Other Than the Expanded Indications

BACKGROUND/AIMS: We aimed to investigate whether the current indications for curative endoscopic resection (ER) of gastric cancer (GC) can be applied to GC caused by adenoma. Additionally, we attempted to identify factors predictive of lesions subsequently found in addition to the expanded indications for ER. METHODS: We retrospectively analyzed 342 patients diagnosed with GC caused by adenoma who underwent ER at a single tertiary center between February 2011 and December 2014. The gross whole tumor size was measured using the endoscopically resected specimen. The microscopic whole tumor size was measured using mapping paper. The estimated cancer size was calculated using the microscopic whole tumor size and the square root of the carcinoma component. RESULTS: A gross whole tumor size ≥3 cm, carcinoma component ≥35%, and gross ulceration were predictive of lesions other than the expanded indications for ER. The overall rate of lymph node metastasis was 0.3% (1/327), which only occurred in one patient with a lesion other than the expanded indications (4.5%, 1/22). CONCLUSIONS: The current indications for curative ER in GC can be applied to GC caused by adenoma. In cases suspected of having lesions other than the expanded indications, patients should be cautiously selected for ER to reduce the risk of an inappropriate procedure.

Clinical Outcomes of Cryopreserved Arterial Allograft Used as a Vascular Conduit for Hemodialysis

This single center cohort study aimed to test the hypothesis that use of a cryopreserved arterial allograft could avoid the maturation or healing process of a new vascular access and to evaluate the patency of this technique compared with that of vascular access using a prosthetic graft. Between April 2012 and March 2013, 20 patients underwent an upper arm vascular access using a cryopreserved arterial allograft for failed or failing vascular accesses and 53 using a prosthetic graft were included in this study. The mean duration of catheter dependence, calculated as the time interval from upper arm access placement to removal of the tunneled central catheter after successful cannulation of the access, was significantly longer for accesses using a prosthetic graft than a cryopreserved arterial allograft (34.4 ± 11.39 days vs. 4.9 ± 8.5 days, P < 0.001). In the allograft group, use of vascular access started within 7 days in 16 patients (80%), as soon as from the day of surgery in 10 patients. Primary (unassisted; P = 0.314) and cumulative (assisted; P = 0.673) access survivals were similar in the two groups. There were no postoperative complications related to the use of a cryopreserved iliac arterial allograft except for one patient who experienced wound hematoma. In conclusion, upper arm vascular access using a cryopreserved arterial allograft may permit immediate hemodialysis without the maturation or healing process, resulting in access survival comparable to that of an access using a prosthetic graft.

Clinical Outcomes of Cryopreserved Arterial Allograft Used as a Vascular Conduit for Hemodialysis

This single center cohort study aimed to test the hypothesis that use of a cryopreserved arterial allograft could avoid the maturation or healing process of a new vascular access and to evaluate the patency of this technique compared with that of vascular access using a prosthetic graft. Between April 2012 and March 2013, 20 patients underwent an upper arm vascular access using a cryopreserved arterial allograft for failed or failing vascular accesses and 53 using a prosthetic graft were included in this study. The mean duration of catheter dependence, calculated as the time interval from upper arm access placement to removal of the tunneled central catheter after successful cannulation of the access, was significantly longer for accesses using a prosthetic graft than a cryopreserved arterial allograft (34.4 ± 11.39 days vs. 4.9 ± 8.5 days, P < 0.001). In the allograft group, use of vascular access started within 7 days in 16 patients (80%), as soon as from the day of surgery in 10 patients. Primary (unassisted; P = 0.314) and cumulative (assisted; P = 0.673) access survivals were similar in the two groups. There were no postoperative complications related to the use of a cryopreserved iliac arterial allograft except for one patient who experienced wound hematoma. In conclusion, upper arm vascular access using a cryopreserved arterial allograft may permit immediate hemodialysis without the maturation or healing process, resulting in access survival comparable to that of an access using a prosthetic graft.

Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. MATERIALS AND METHODS: A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped. RESULTS: In univariate survival analysis, tumor grade (p 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. CONCLUSION: From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

Case of a Metastatic Solitary Fibrous Tumor Presenting as Gastrointestinal Bleeding / 대한내과학회지

Metastatic cancers of the stomach are rare. Metastatic diseases of the stomach can occur with melanoma and other primary tumors of the breast, lung, ovary, liver, colon, and testis; however, breast cancer is the most common. Other rare malignant tumors that can involve the stomach include Kaposi's sarcoma, myenteric schwannoma, glomus tumor, small cell carcinoma, and parietal cell carcinoma. On the other hand, solitary fibrous tumors of the pleura are rare soft tissue sarcomas, and most are benign; however, 13 to 36% may be malignant. Metastases may occur in extrathoracic sites, such as the liver, central nervous system, spleen, adrenal gland, and bone. We herein report a case of a 75-year-old man with previously diagnosed brain and liver metastases. He developed a stomach metastasis from a malignant solitary fibrous tumor and presented with gastrointestinal bleeding symptoms.

Histopathologic Analysis of BI-RADS Category 4a Breast Lesions Diagnosed by Ultrasonography / 한국유방암학회지

PURPOSE: We analyzed the histopathologic findings of the patients with ultrasongraphic Breast Imaging Reporting and Data System (BI-RADS) Category 4a breast lesions to determine which patient can be excluded from any invasive, diagnostic procedure in the future. METHODS: Of the 180 cases of BI-RADS Category 4a breast lesions that were diagnosed with ultrasonography during a 6 month-period, 132 cases were pathologically confirmed and these were analyzed retrospectively. Four benign cases that did not undergo any further procedure after fine needle biopsy and 6 malignant cases (4.5%) were excluded from this study. RESULTS: Of the 122 cases, 77 cases (63.1%) showed homogeneous benign finding, and 45 cases (36.9%) showed heterogeneous finding that was made up of two or more different pathologic lesions. Fibroadenoma (55.8%) was the most frequent pathologic finding in the cases with homogeneous finding, followed by fibrocystic change (14.3%), and fibrosis (7.8%). The cases with heterogeneous finding presented fibrocystic change (55.5%), microcalcification (48.8%), ductal hyperplasia (42.2%), and fibroadenoma (31.1%) in the order of frequency. CONCLUSION: Lesion with heterogeneous histopathologic nature was the most frequent finding defined as category 4a in breast ultrasonography, followed by fibrodenoma, fibrocystic change, microcalcification, and ductal hyperplasia. Refining more specific ultrasonographic findings of these lesions would guarantee that radiologists exclude more benign lesions from category 4a.

Expression of the Markers for the Mammary Stem Cells and the Cellular Lineages of the Mammary Gland on Ductal Carcinoma In Situ / 한국유방암학회지

PURPOSE: Breast Cancer is an inter-tumoral and intra-tumoral heterogeneous disease. It remains unclear whether this heterogeneity results from different target cells or from different subsets of genetic abnormalities, otherwise from both. We postulated that in addition to genetic cloning, a variety of cells that exist during the defined developmental stages of the human mammary gland could give rise to the heterogeneity of breast cancer. To verify this postulation, we have analyzed pure ductal carcinoma in situ (DCIS) for the expression of the biomarkers that represent the mammary stem cell, the early progenitor cells, and the glandular and myoepithelial cells of the mammary gland. METHODS: We investigated the relationship between the immnuohistochemical expression of the mammary development-associated biomarkers {cytokeratin-18 (CK18), cytokeratin-6 (CK6), alpha-smooth muscle actin (SMA), Wnt-1, Notch 3} and some other factors {the menopausal status, the estrogen receptor (ER) status, the progesterone receptor (PR) status, c-erbB-2, and the number of tumor foci} in 26 cases of DCIS. RESULTS: All 26 cases included in this study showed the positive expressions of CK18 and SMA. The expression of all the markers was not correlated with the menopausal status. The positive expression of CK6 had a statistically significant relationship with a negative estrogen receptor (p=0.014), positive c-erbB-2 (p=0.048), high nuclear grade (p=0.001), and single focus of DCIS (p=0.017). The expression of Wnt-1 and Notch 3 did not have significant correlation with any factors. However, the positive expression of Wnt-1 showed a tendency of a negative ER (p=0.061) and the positive expression of Notch 3 also showed a tendency of a negative ER (p=0.086) and a high nuclear grade (p=0.086). CONCLUSION: The CK6 positive tumor is thought to originate from the more primitive cells compared to the CK6 negative tumor. Unifocality of the CK positive tumor might result from the arrest of differentiation of the original cell after disease affection. DCISs could be categorized into the CK6 positive and negative groups.

Jarcho-Levin syndrome: a report of an autopsy case with cytogenetic analysis

Jarcho-Levin syndrome (JLS) is a condition manifested by malformations of vertebral bodes and related ribs. There are two major subtypes spondylocostal dysostosis and spondylothoracic dysostosis, with different survival rates, associated malformations, and inheritance patterns. We have experienced an autopsy case of a premature female fetus with multiple congenital anomalies. She was 30 weeks of gestational age, born as the second baby of twins and expired shortly after birth. A post-mortem examination revealed multiple abnormalities including cervicothoracic hemivertebrae, a diminished number of right-sided ribs, and pulmonary hypoplasia with left diaphragmatic hernia. In addition, there were anomalous rotation of the foregut, unfused pancreas and anomalous drainage of the superior vena cava. Chromosomal analysis showed 46, XX, del(4)(q ter).