Neutrophil to Lymphocyte Ratio after Treatment Completion as a Potential Predictor of Survival in Patients with Triple-Negative Breast Cancer / 한국유방암학회지

Purpose@#Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. @*Methods@#In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). @*Results@#In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Twothirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. @*Conclusion@#Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying highrisk patients with TNBC.

Meeting Highlights: The First Korean Breast Cancer Treatment Consensus Conference / 한국유방암학회지

The first Korean Breast Cancer Treatment Consensus Conference Expert Panel reviewed and endorsed new evidence on aspects of local and regional therapies and diagnostic procedures that support the conservative application of results from recent clinical trials. This conference clarified the barriers that limit the application of recent clinical trial results, such as questions about level of evidence, differences between the setting of clinical trials and that of daily clinical practice, and medical necessities and environment. Detailed decisions recommended for the treatment and diagnosis, according to the from the consensus conference, are recorded including details of the votes. These recommendations differed in the degree of support for clinical consideration of disease extent and host factors, medical necessities, and environment.

Longer Survival in Patients with Breast Cancer with Cyclin D1 Over-Expression after Tumor Recurrence: Longer, but Occupied with Disease / 한국유방암학회지

PURPOSE: The effect of cyclin D1 overexpression on breast cancer outcomes and prognosis is controversial, even though amplification of the cyclin D1 gene, CCND1, has been shown to be associated with early relapse and poor prognosis. In this study, we examined the relationship between cyclin D1 overexpression and disease-specific survival (DSS). We also analyzed survival in patients who experienced recurrence. METHODS: We retrospectively analyzed data from patients diagnosed with ductal carcinoma between April 2005 and December 2010. We examined clinicopathologic factors associated with cyclin D1 overexpression and analyzed the influence of cyclin D1 on recurrence-free survival and DSS. RESULTS: We identified 236 patients diagnosed with primary breast cancer who completed all phases of their primary treatment. Cyclin D1 overexpression was significantly associated with longer DSS (5-year DSS, 89.9% in patients without cyclin D1 overexpression vs. 98.9% in patients with cyclin D1 overexpression; p=0.008). Multivariate analysis also found that patients with cyclin D1 overexpressing tumors had significantly longer disease-specific survival than patients whose tumors did not overexpress cyclin D1, with a hazard ratio for disease-specific mortality of 7.97 (1.17-54.22, p=0.034). However, in the group of patients who experienced recurrence, cyclin D1 overexpression was not significantly associated with recurrence-free survival. Cyclin D1 overexpression was significantly associated with increased survival after disease recurrence, indicating that cyclin D1 overexpression might be indicative of more indolent disease progression after metastasis. CONCLUSION: Cyclin D1 overexpression is associated with longer DSS, but not recurrence-free survival, in patients with breast cancer. Longer postrecurrence survival could explain the apparent inconsistency between DSS and recurrence-free survival. Patients with cyclin D1-overexpressing tumors survive longer, but with metastatic disease after recurrence. This information should spark the urgent development of tailored therapies to cure these patients.

ROS1 Expression in Invasive Ductal Carcinoma of the Breast Related to Proliferation Activity

PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.

Usefulness of Pretreatment Neutrophil to Lymphocyte Ratio in Predicting Disease-Specific Survival in Breast Cancer Patients / 한국유방암학회지

PURPOSE: The purpose of this study was to investigate the prognostic impact of pretreatment neutrophil to lymphocyte ratio (NLR) on breast cancer in view of disease-specific survival and the intrinsic subtype. METHODS: We retrospectively studied patients diagnosed with primary breast cancer that had completed all phases of primary treatment from 2000 to 2010. The association between pretreatment NLR and disease-specific survival was analyzed. RESULTS: A total of 442 patients were eligible for analysis. Patients with higher NLR (2.5 < or =NLR) showed significantly lower disease-specific survival rate than those with lower NLR (NLR <2.5). Higher NLR along with negative estrogen receptor status and positive nodal status were independently correlated with poor prognosis, with hazard ratio 4.08 (95% confidence interval [CI], 1.62-10.28), 9.93 (95% CI, 3.51-28.13), and 11.23 (95% CI, 3.34-37.83), respectively. Luminal A subtype was the only intrinsic subtype in which higher NLR patients showed significantly poor prognosis (87.7% vs. 96.7%, p=0.009). CONCLUSION: Patients with an elevated pretreatment NLR showed poorer disease-specific survival than patients without elevated NLR, most evident in the luminal A subtype. Further validation and a feasibility study are required before it can be considered for clinical use.

The diagnostic values of preoperative laboratory markers in children with complicated appendicitis / 대한외과학회지

PURPOSE: Accurate diagnosis and optimal management of acute appendicitis, despite being the most common surgical emergency encountered in emergency departments, is often delayed in pediatric patients due to nonspecific symptoms and communication barriers, often leading to more complicated cases. The aim of this study is to investigate the diagnostic significance of common laboratory markers. METHODS: A total of 421 patients aged 15 and younger underwent surgical treatment for acute appendicitis. We conducted a retrospective analysis for white blood cell (WBC), C-reactive protein (CRP) and bilirubin. All patients were classified into simple or complicated appendicitis groups based on postoperative histology. RESULTS: The mean age of the patients in the complicated appendicitis group was younger than that in the simple group (P = 0.005). WBC, CRP and bilirubin levels were significantly higher in the complicated appendicitis group (P < 0.001, <0.001, 0.002). The relative risk for complicated appendicitis was calculated using age, WBC, CRP and bilirubin. Elevated CRP levels were associated with the highest risk for complicated appendicitis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.38 to 4.65) followed by WBC (HR, 2.42; 95% CI, 1.07 to 5.46) and bilirubin (HR, 2.04; 95% CI, 1.09 to 3.82). The most sensitive markers for diagnosing complicated appendicitis were WBC (95.2%) and CRP (86.3%). Bilirubin levels showed the highest specificity at 74.8%. CONCLUSION: The risk of complicated appendicitis was significantly higher in patients younger than 10 years old. Preoperative WBC, CRP and bilirubin have clinical value in diagnosing complicated appendicitis with a HR of 2.0 to 2.5. Our results suggest that the utilization of WBC, CRP, and bilirubin can assist in the diagnosis of complicated appendicitis in pediatric patients, allowing prompt diagnosis and optimal management.

HDAC1 Expression in Invasive Ductal Carcinoma of the Breast and Its Value as a Good Prognostic Factor

BACKGROUND: Histone deacetylase 1 (HDAC1) is associated with the expression and function of estrogen receptors and the proliferation of tumor cells, and has been considered a very important factor in breast tumor progression and prognosis. Several studies have reported an association between HDAC1 expression and poorer prognosis in cancers including breast cancer, with a few exceptions. However, because of the dearth of studies on HDAC1 expression in breast cancer, its significance for breast cancer prognosis has not been well defined. Therefore, we examined HDAC1 expression in invasive ductal carcinoma (IDC), the most common breast cancer, and investigated its potential prognostic significance. METHODS: We used 203 IDC tissue samples. Immunohistochemical stains for HDAC1 and real-time polymerase chain reaction for HDAC1 mRNA were performed and the results were compared to generally well-established prognostic factors in breast cancer and patient survival rates. RESULTS: HDAC1 expression was significantly reduced in proportion to higher histologic grade, higher nuclear pleomorphism score, and higher mitotic counts, and with lower estrogen receptor expression. Furthermore, it was significantly associated with the survival rate. CONCLUSIONS: HDAC1 expression is a good prognostic indicator in IDC.

Expressional Difference of RHEB, HDAC1, and WEE1 Proteins in the Stromal Tumors of the Breast and Their Significance in Tumorigenesis

BACKGROUND: Fibroadenoma (FA) and phyllodes tumor (PT) are stromal tumors of breast and are histologically similar. There are no established differences in tumorigenesis and oncogene expression among them. Ras homolog enriched in brain (RHEB) plays an important role in cell growth and cell-cycle control, histone deacetylase 1 (HDAC1) is an important factor in breast tumor progression and prognosis, and WEE1 homolog (WEE1) functions as a tumor suppressor. No studies on the expressional differences of these proteins in FA and PT have been reported to date. METHODS: The expression of these proteins in FA, PT, and normal breast was compared. We used 102 cases of FA and 25 cases of benign PT. RESULTS: In epithelial cells, the expression of RHEB, HDAC1, and WEE1 was lowest in PT, higher in FA, and most enhanced in normal breast. In addition, the expression of RHEB and HDAC1 was higher in the stromal cells of PT than in FA and normal breast. CONCLUSIONS: Both epithelial and stromal cells of FA and PT express these proteins, which indicates that epithelial cells play an important role in the development of stromal tumors. In addition, the expressional differences of these proteins may be associated with the tumorigenesis of breast stromal tumors.

Giant Meckel's Diverticulum Associated with a Congenital Diaphragmatic Hernia

Giant Meckel's diverticulum is a very rare lesion and its association with a congenital diaphragmatic hernia has not been reported previously. We report a case of newborn with a giant Meckel's diverticulum and congenital diaphragmatic hernia. A large round atypical air-filled bowel segment was found by chest radiography preoperatively, and a giant Meckel's diverticulum was located within the left hemithorax during surgery.

Acute Gastric Dilatation and Calculous Cholecystitis in Duchenne's Muscular Dystrophy

With Duchenne's muscular dystrophy, there are many descriptions from the view of skeletal muscle disorders. However, the functional impairment of smooth muscle can cause fatal problems. A case of a 13-year-old boy, with Duchenne's muscular dystrophy, who present with severe abdominal pain from acute gastric dilatation and acute calculous cholecystitis, is reported. The case is discussed, with a review of the literature.

The Prognostic Factors in Multiple Traumas in Children

PURPOSE: Trauma is the leading cause of death among children age 1 to 15 years. The initial assessment of injured children is also important for the adequate treatment and transfer of these patients when required. A number of trauma scoring systems have been applied to the pediatric trauma population, with the Pediatric Trauma Score (PTS) being specifically developed as a triage tool for specifically for children. The ability of the PTS to predict the severity of an injury and mortality, and the value of the PTS were evaluated. METHODS: Seventy patients younger than 16 years of age, with multiple organ injuries, were assessed for 5 years, from January 1, 1997 to December 31, 2001. The demographic and clinical variables were retrospectively analyzed and the PTS assessed. RESULTS: Motor vehicle related injuries caused the majority of the multiple organ injuries the children, with liver injuries accounting for the greatest numbers. The survivals showed differences in relation to age, sex, number of injured organs and PTS, but no statistical significance was proved from a univariate analysis. From the multivariated analysis, only the PTS showed statistical significance. There were 5 deaths where the PTS was more than 9 points, was accounting for 55% of all mortalities. CONCLUSION: The PTS is an important triage for injured children, but could not reflect the prognosis of the injured patients when the clinical appearances were not reflected.

The Role of Interstitial Cells of Cajal in Congenital Megacolons and Idiopathic Megacolons

The etiology of several motility disorders, including persistent megacolon after definitive surgery for Hirschsprung's disease, meconium ileus which is not associated with cystic fibrosis and idiopathic megacolon, is still unclear. Interstitial cells of Cajal (ICC) are thought to modulate gut motility as gastrointestinal pace maker cells. The aim of this study was to evaluate the role of ICC in the bowel walls of the patients (n=15) who had variable motility disorders. The ICC were identified by immunohistochemical staining using an anti-C-Kit antibody and the results were compared with control specimens (n=2). The control group (G1) showed evenly distributed ICC in their bowel walls. The second group (G2, n=5) who had normal bowel movements after Duhamel procedures and the third group (G3, n=4) who had persistent megacolon after Duhamel procedures showed absent or scarcely distributed ICC in their aganglionic bowels. The ICC were identified by immunohistochemical staining using an anti-C-Kit antibody and the results were compared with control specimens (n=2). The control group (G1) showed evenly distributed ICC in their bowel walls. The second group (G2, n=5) who had normal bowel movements after Duhamel procedures and the third group (G3, n=4) who had persistent megacolon after Duhamel procedures showed absent or scarcely distributed ICC in their aganglionic bowels. Whereas ICC were evenly distributed in the ganglionic bowels of G2, they were not seen or scarecely distributed in the ganglionic bowels of G3. Two patients (G4) who suffered from idiopathic megacolon showed absence or decrease of ICC in spite of presence of ganglion cells in their colons. Four neonates (G5) who underwent ileostomy because of meconium obstruction showed absent or markedly decreased ICC in the colon at the time of ileostomy and the distribution of ICC was changed to a normal pattern at the time of ileostomy closure between 39-104 days of age and their bowelmotility were restored after that. The results suggest that lack of ICC caused reduce motility in the ganglionic colons and it may be responsible for the development of various motility disorders. Delayed maturity of ICC may also play a role in the meconium obstruction of neinates.

The Impacts of the Prenatal Ultrasonogram on the Pediatric Surgery

PURPOSE: Prenatal diagnosis of congenital anomalies provides the information for the perinatal treatment, which can be beneficial to the patients. Yonsei University is one of the largest tertiary referral centers in Korea and its achievement in pediatric surgery is representative figure of pediatric surgery in Korea. This achievement is used to assess the impacts of prenatal ultrasonograms on the doutcomes of prenally diagnosed anomalies in the neonates. METHODS: Between 1991 and 2000, 41,458 prenatal ultrasonograms were performed on the pregnant women and the fetal abdominal abnormalities were suspected in 165 fetuses. Of these, 87 fetuses were delivered and the abnormalities were finally confirmed. Theses 87 fetuses was the basis of this study in terms of their prenatal and final diagnosis with the outcomes. RESULTS: Among 87 fetuses, 17 cases were terminated in relation to the maternal health or multiple anomalies. Of the remaining 70 fetuses, 55 patients survived. Among the prenatal diagnoses of 87 fetuses, final diagnosis were made from 75 fetuses and the accuracy of the prenatal diagnosis was found to be 60.0% (45/75). Surgical correction was necessary in 44 cases to confirm the diagnosis and of these, 40 patients survived after the surgical correction. CONCLUSION: Prenatal diagnosis of the congenital anomalies will improve postnatal outcomes by proper surgical management. However, it can affect the rate terminations of pregnancies even though its accuracy is not so high. To advance the knowledge of the fetal pathophysiology, pediatric surgeons must play an important role in the prenatal diagnosisin relation to the postnatal treatment of the anomalies.

Laparoscopic Meckel's Diverticulectomy in Children

Meckel's diverticulum is one of the common causes of gastrointestinal bleeding in the pediatric patient requiring laparotomy. Two children with Meckel's diverticulum have been successfully treated by laparoscopic excision. Both patients recovered without incident and were discharged at 3 and 5 days after surgery. The authors believe that laparoscopic diverticulectomy is a safe, effective, and minimal invasive treatment of Meckel's diverticulum in children.

A Case of Successful Hepatic Resection after Local Radiotherapy with Combined Transarterial Chemoinfusion in Hepatoblastoma

It has been widely accepted that complete surgical resection of hepatoblastoma is essential for long-term survival. But unfortunately less that 50% of hepatic tumors in children can be totally removed at the time of diagnosis. This report is to present the experience of successful resection of hepatoblastoma after concurrent radiotherapy with transarterial chemoinfusion in a child. We believe this modality of treatment enables complete resection of unresectable hepatoblastoma, which is resistant to the systemic chemotherapy.

The Usefulness of Magnetic Resonance Cholangiography in the Diagnosis of Biliary Atresia

PURPOSE: To evaluate the usefulness of magnetic resonance cholangiography(MRC) for the diagnosis of biliary atresia in infantile cholestatic jaundice. METHODS: Fifty consecutive infants with cholestatic jaundice underwent single-shot MRC for 3 years. The radiologic diagnosis of non-biliary atresia with MRC was based on visualization of the common bile duct and common hepatic duct. The diagnosis of biliary atresia was based on non-visualization of either the common bile duct or common hepatic duct. The final diagnosis of biliary atresia or non-biliary atresia was made with operations or clinical follow-up until jaundice resolved. RESULTS: MRC could clearly visualized the gallbladder, cystic duct, common hepatic duct, common bile duct, both intrahepatic ducts and second order intrahepatic ducts in small neonates and infants. MRC had accuracy of 98%, sensitivity of 100% and specificity of 96% for diagnosis of biliary atresia as the cause of infantile cholestatic jaundice. CONCLUSIONS: MRC is a very reliable noninvasive imaging study for diagnosis of biliary atresia in infants with cholestatic jaundice.

Expression of Neural Cell Adhesion Molecule (NCAM) and Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Aganglionic Bowel of Hirschsprung's Disease

The pathophysiology of Hirschsprung's disease (HD) is not fully understood, but recent studies have disclosed that neural cell adhesion molecule (NCAM) and glial cell line-derived neurotrophic factor (GDNF) play important roles in the formation of aganglionic bowel of Hirschsprung's disease. To evaluate the roles of NCAM and GDNF in HD, immunohistochemical analysis was performed using formalin-fixed and paraffin-embedded tissue sections. On the basis of the results, we tried to evaluate them as diagnostic markers. The specimens were obtained from 7 patients with HD who underwent modified Duhamel operation. The diagnosis was based on the clinical findings and the absence of ganglion cells in the nerve plexuses by routine microscopy. NCAM immunoreactivity was found in the nerve plexuses and scattered nerve fibers in the smooth muscle layers of ganglionic segments. In aganglionic segments, the number of NCAM positive nerve fibers in the smooth muscle layers was significantly reduced compared with ganglionic segments. In two cases the nerve plexuses in aganglionic segments, NCAM was negligible. The smooth muscle cells showed diffuse immunoreactivity for GDNF and the staining intensity was not different in the aganglionic and ganglionic segments. However, higher expression of GDNF in the nerve plexus of the ganglionic segments was noted comparing to aganglionic segments. These data suggest that both NCAM and GDNF may play important roles in pathogenesis of Hirschsprung's disease and immunohistochemical staining for NCAM can be used as an ancillary diagnostic tool for HD.

The results of combined therapeutic modalities for hepatoblastoma

In hepatoblastoma, encouraging cure rates have been achieved with recent advances in chemotherapy and surgical techniques. The aim of this study is to evaluate the role of combined therapeutic modalities and surgical resection in hepatoblastoma. Fifteen cases of hepatoblastoma were treated from January 1993 to August 2000. Six patients had resectable tumors at initial diagnosis. All underwent surgical resection and in four patients postoperative adjuvant chemotherapy was needed. Nine out of 15 patients had unresectbale tumors at initial diagnosis, and preoperative chemotherapy was applied. There was one operative mortality and 14 patients showed good prognosis after surgery. Although various treatment modalities should be combined for the unresectable hepatoblastoma, surgical resection remains the major curative procedure.

A Successful Slide Cricotracheoplasty in Congenital Cricotracheal Stenosis

Slide tracheoplasty, as a treatment for congenital tracheal stenosis, has been recently reported to have good results and quite a number of advantages as compared with conventional tracheoplasties. The aim of this study is to report a new surgical technique modified from the slide tracheoplasty, "the slide cricotracheoplasty" for the congenital cricotracheal stenosis. A girl was born by Cesarean section and the diagnosis of esophageal atresia (Gross type C) and cricotracheal stenosis (30% of total length of trachea) was established. Esophageal atresia was successfully corrected at the 8th day of life. At the 31st day of life, corrective surgery for congenital cricotracheal stenosis, the slide cricotracheoplasty, was performed with success. Slide cricotracheoplasty is almost the same procedure as slide tracheoplasty except for two technical features. First the cricoid cartilage was split on its anterior surface. Second the split cricoid cartilage was fixed to pre vertebral fascia to maintain enough space to accommodate the sliding caudal segment of trachea because of the stiffness of the cricoid cartilage. We believe that the sliding cricotracheoplasty is a new surgical technique for congenital cricotracheal stenosis that has similar results and advantages as the sliding tracheoplasty.

Arterial Embolization for the Ruptured Splenic Artery Pseudoaneurysm in a Child

Pseudoaneurysm of splenic artery may arise from a vascular erosion by the inflammatory processes around the splenic artery, particularly in acute pancreatitis and chronic pancreatitis, which may cause rupture of pseudoaneurysm and life threatening hemorrhage. Collective experience with this massive hemorrhage is attended by a high mortality rate even with prompt therapy, and conservative management is associated with an almost 100 per cent of mortality rate. Identification of the bleeding site at laparotomy may be exceedingly difficult, which makes the preoperative detection of bleeding source desirable. Peripancreatic vascular lesions can be identified by angiography, and in selected cases the risk of urgent operation to control massive hemorrhage may be obviated by embolization. The authors have recently experienced a case of ruptured splenic artery pseudoaneurysm combined with a pancreatic pseudocyst in a 6 years old boy. A bolus enhanced CT scan and angiography were essential to confirm these complications of pancreatic pseudocyst. We managed this child successfully with an urgent procedure of transcatheter arterial embolization and another elective surgery of pancreatic pseudocyst.