Predictive Factors for Non-Response to Neoadjuvant Chemotherapy for Breast Cancer

Purpose@#Neoadjuvant chemotherapy (NAC) can effectively downstage locally advanced breast cancer; however, in some cases the cancer remains clinically stable and in others, there is disease progression. Although factors predictive of the response to NAC have been established, those for a non-response remain unknown. This study investigated factors predicting a stable or progressive disease course, and the extent of the response, after NAC based on anthracycline and cyclophosphamide (AC), with or without taxane. @*Methods@#Data were collected retrospectively by reviewing medical records of patients who received NAC for breast cancer using AC, with or without taxane between January 2013 and December 2017. Patients with clinically stable or progressive disease after NAC were compared statistically with those who achieved a partial or complete response. @*Results@#In total, 297 patients received NAC with AC and 196 patients received AC followed by taxane. Of these, 45 (15.2%) and 64 (32.6%) patients respectively, showed no response (i.e., stable or progressive disease). Factors related to non-response after AC included large pretreatment tumor size, clinical T3 status, and high histologic grade. Factors related to non-response after taxane included clinical T3 status and estrogen receptor or progesterone receptor positivity. @*Conclusion@#Clinical T3 stage, grade III histological grade, and estrogen or progesterone receptor positivity were predictors of no response to NAC for breast cancer.

Intraoperative Specimen Mammography for Margin Assessment in Breast-Conserving Surgery / 한국유방암학회지

Comparision of Needlescopic Appendectomy versus Conventional Laparoscopic Appendectomy in Children / 대한내시경복강경외과학회지

PURPOSE: This clinical study evaluated the feasibility of needlescopic appendectomy (NA) in young patients with acute appendicitis, and we compare the outcome of this new technique with that of conventional laparoscopic appendectomy (LA). METHODS: Two groups of young patients who underwent laparoscopic appendectomy at Sanggye Paik Hospital between January 2009 and December 2009 were studied. In the first group, a 2-mm instrument appendectomy was performed in 13 patients. These patients were compared with the second group, which were 21 patients who underwent conventional laparoscopic appendectomy. Statistical significance was set at p values<0.05. RESULTS: The patient demographics and operative findings were similar in both groups. There was no conversion to open appendectomy in either group. Postoperative ileus was occurred in 3 patients who underwent LA, but there was no statistical difference between the both groups (p=0.154). The needlescopic group had a shorter mean operative time (p=0.65), but there was no statistically significance. The mean hospital stay was significantly shorter (p=0.026) in the needlescopic group than that in the conventional laparoscopic group. CONCLUSION: According to our experience, needlescopic laparoscopic appendectomy is a safe and feasible procedure as compared with that of conventional laparoscopic appendectomy in young patients.

Prognostic Significance of p27(kip1) Expression in Node Negative Colorectal Carcinoma

PURPOSE: Dukes' A & B colorectal cancer patients are often excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, actually 20 ~ 30% of these patients suffer from recurrent disease, so it would be helpful for these patients of recurrent disease to be able to select a high risk group. METHODS: In 78 Dukes' A & B colorectal cancers, we investigated by immunohistochemistry the role of molecular markers, such as p27(kip1), p53, Ki-67, and Skp2, in identifying high-risk patients. RESULTS: Patients with low p27(kip1) expression showed poor overall survival compared to those with high p27(kip1) expressions (55.3 versus 66.7 months, P=0.018). The only significant factor associated with p27(kip1) expression was p53 expression. The low p27(kip1) expression and positive p53 expression group had poor overall survival (54.3 months, P=0.036). CONCLISIONS: In a node-negative colorectal carcinoma, the molecular marker p27(kip1) does not play an independent prognostic role, but it may have prognostic significance in correlation with other markers such as p53, Ki-67, and Skp2. The assessment of molecular alterations may be useful to node-negative colorectal patients in identifying the high risk group that may benefit from adjuvant chemotherapy.

Solitary Schwannoma in the Breast: A Case Report

Schwannoma (neurilemoma) is a benign nerve tumor derived from the nerve sheath. The most common locations are the flexor surfaces of the extremities, and the head and the neck. Schwannoma of the breast is unusual. To our knowledge, few studies have reported the radiologic appearance of schwannoma in the breast and there has been only one report from Korea (1-3). This tumor can be clinically and radiologically considered to be fibroadenoma, which is a common benign tumor of the breast. We describe the mammographic and sonographic findings of a case of schwannoma in the breast.

The Policy Proposal for Effective Prevention and Management of Breast Cancer / 한국유방암학회지

Breast cancer is the most common cancer in Korean women since 2001 and needs national interests. The incidence of breast cancer is increasing with new breast cancer cases reaching more than 10,000 cases annually. But, there are some difficulties in breast cancer control; first, the National Cancer Screening Program is ineffective and of low quality, second, the lack of psychosocial care for mastectomized patients, third, the lack of national care for terminal cancer patients. For effective breast cancer control, we need special support for breast cancer awareness campaign, activation of breast cancer registry, development of clinical practice guideline, development of hospice program, breast cancer research, and upgrading its guarantee on breast cancer treatment. The Korean Breast Cancer Society should have the leading role in solving the current problems, but moreover, we cannot overemphasize the need for national support.

The Clinical Significance of Cyclooxygenase 2 Expression in Colorectal Cancer

PURPOSE: Epidemiologic studies have indicated that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies have demonstrated the increased expression of cyclooxygenase-2 (COX-2) in human colorectal cancer tissues. However, the role of COX-2 in colorectal cancer has not been fully established. The aim of this study was to clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: We performed immunohistochemical straining for COX-2 expression in 124 human colorectal cancer specimens. COX-2 expression was then compared with clinicopathologic factors and survival outcomes. RESULTS: COX-2 was expressed in the cytoplasm of the cancer cells. COX-2 expression was noted in 86.3% of the cancer patients and significantly correlated with the histologic type. The depth of invasion, tumor size, lymph node metastasis and stage were not correlated with COX-2 expression. Multivariate analysis for the factors associated with survival showed that serum CEA, size, depth and lymph node involvement correlated with survival, but COX-2 expression had no correlation. CONCLUSION: These data suggest that COX-2 expression in primary lesion of colorectal cancer may not be a useful marker for evaluating prognosis. However, further studies are necessary for identification of the roles in colorectal carcinogenesis.

Expression of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in Colorectal Cancer

PURPOSE: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogeneous factors of human tumor progression. The aims of this study is to investigate the correlation between the expression of COX-2 and iNOS and to assess the clinicopathological significance of COX-2 and iNOS expression in patients with colorectal cancer. METHODS: One hundred and five patients, who underwent curative resection of colorectal cancer from 1994 to 1997 were analyzed retrospectively. The monoclonal antibody to the COX-2 and iNOS were used for the immunohistochemical analysis. RESULTS: In 105 patients the COX-2 and iNOS positive rate were 86.7% and 69.5% respectively. There was significant correlation between COX-2 and iNOS expression (r= 0.378, P<0.01), that is, the lesions which expressed high level of COX-2 also expressed iNOS highly. The proliferation index (Ki-67 labeling index) was correlated with iNOS (P=0.013), and the microscopic differentiation with COX-2 (P=0.004). However, the expression of COX-2 and iNOS proteins did not correlate with any other clinicopathological parameters including patient survival. CONCLUSIONS: Although the pattern of positive expression was similar in both enzymes, the expression of both enzymes was not related to prognosis in patients with colorectal cancer. But COX-2 and iNOS seems to have a role not only in carcinogenesis but also tumor cells proliferation. To evaluate the exact role of these enzymes, further studies of the apoptosis and cancer metastasis and of links between the cancer related factors of COX-2 and iNOS are warranted.

Clinical Value of the Change in the Serum Carcinoembryonic Antigen (CEA) Level after Curative Surgery in Colorectal Cancer

PURPOSE: This retrospective study was designed to evaluate the clinical value of changes in the serum carcinoembryonic antigen (CEA) level after curative surgery in colorectal cancer patients. METHODS: The clinical value of preoperative serum CEA and dCEA (postoperative 7-day CEA/preoperative CEA) in 115 patients with colorectal cancer, who underwent curative surgery at our Department of General Surgery from 1994 to 1997, was investigated. RESULTS: The preoperative CEA level was significantly associated with histologic differentiation (P=0.035) and reccurence (P=0.044), but not gender, tumor size, lymph node metastases, Duke's stage, and vascular invasion. dCEA was significantly associated with lymph-node metastases (P=0.017), histologic differentiation (P=0.024), Duke's stage (P=0.021), recurrence (P=0.008), and survival rate (P=0.0379). Especially, in the abnormal preoperative CEA level (>5 ng/mL) group, if dCEA was more than 0.5, these patients had a very poor prognosis (P=0.0003). CONCLUSIONS: dCEA was associated with more clinicopathologic prognostic factors than preoperative CEA, especially with survival rate. Therefore, we expect dCEA to be a more useful tool for predicting patient outcome.

Expression of Chk2 and P53 in Sporadic Breast Cancer / 한국유방암학회지

PURPOSE: In response to DNA damage, Chk2 (CHEK2) is involved in cell cycle checkpoint. Chk2 is activated by the upstream ATM kinase and then directly phosphorylate p53 at serine 20. Other substrates for Chk2 are BRCA1, Cdc25A, Cdc25C, mdm2. Germ line mutations of Chk2 have been identified in Li-Fraumeni syndrome with normal p53 alleles. There are few reports on somatic mutations of Chk2 in osteosarcoma, lung cancer, breast cancer, testicular germ cell tumor, ovarian cancer. In this study, we have analyzed 30 breast cancer specimens to understand the relationship of Chk2 and P53 in the pathogenesis of sporadic breast cancer. METHODS: We performed an immunohistochemical studies for Chk2, P53 in the specimens from 30 breast cancer patients. We designed entire intronic primers and searched for Chk2mutations in 7 cases by DNA sequence analysis of the entire coding region. RESULTS: Seven of 30 (23.3%) breast cancers had reduced immuno-expression of Chk2, one of them (1/7, 14.3%) showed a p53 immuno-expression and all of them revealed no Chk2 mutation. CONCLUSION: Expression of Chk2 protein more reduced in breast cancer with no abnormal p53 immuno-expression. No Chk2 mutation was found in all of Chk2 reduced expression, we hypothesize that there may be a posttranscriptional/ posttranslational mechanism (s) in breast caner to downregulate Chk2 protein expression.

Relationship between E2F1 Expression and Clinical Outcome in Node-Positive Breast Cancer / 한국유방암학회지

PURPOSE: This study was performed to investigate whether the E2F1 protein expression can be used as a prognostic factor in clinical breast cancer. METHODS: The expressions of E2F1 and retinoblastoma protein (pRB) were analyzed in 165 lymph node positive breast cancers. All patients underwent adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) after curative surgery. RESULTS: E2F1 was expressed in 43.6% and pRB was expressed in 46.1%. E2F1 expression was significantly increased in pRB-expressing tumors and was associated with S-phase fraction. By univariate survival analyses, E2F1 expression and ER were the significant prognostic factors for the disease recurrence and patient survival. E2F1 was the only significant prognostic factor for the patient outcome after FAC chemotherapy by multivariate analysis. CONCLUSION: Conclusion The results of the current study indicate that abnormal expression of E2F1 and pRB is prevalent and are intimately associated with each other in clinical breast cancer. A significant association between E2F1 expression and patient survival after FAC chemotherapy mondates a further validation study.

The Correlations between the Expression of Cyclin E and Clinical Features of the Primary Breast Cancer

PURPOSE: Cyclin E is a key regulatory protein in the G1-S transition during the cell cycle. The correlations between cyclin E protein and the clinical features of breast cancer were investigated in order to evaluate its clinical utility in invasive breast cancer. METHODS: An immunohistochemical assay for cyclin E was performed in 101 consecutive invasive breast cancers. The correlation between cyclin E expression and the clinicobiological parameters including patient survival was analyzed. RESULTS: Cyclin E expression was observed in 50 patients (49.5%). The scoring of the cyclin E expression level was divided into low (or=25%). In high nuclear grade tumors, cyclin E overexpression was much higher than that in low nuclear grade tumors (P=0.049). In the younger age group (<50 yrs), cyclin E expression was significantly higher than the older age group (P= 0.016). No significant correlation was observed between cyclin E and the tumor size, lymph node status, hormonal receptor status, histological grade, mitotic index and Ki67. In multivariate analysis, only the lymph node status was significantly associated with the patients' outcome (P= 0.002). CONCLUSION: Cyclin E overexpression did not have prognostic impact on the patients' survival rate in invasive breast cancer. In high nuclear grade tumors, the cyclin E expression level was much higher. The definite value of cyclin E as a clinicobiologic marker should be further investigated by prospective studies with other cell regulatory proteins.

Interrelation of Cyclin D1, Cyclin E, and p27Kip1 Expression on Tissue Arrays of Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the clinical impact of the altered expression of cell cycle regulators in stage I and II breast cancers. MATERIALS AND METHODS: The interaction between cyclin D1/E and p27Kip1 expressions were analyzed using tissue microarray (TMA) technology in 133 breast cancers. Data from the immunohistochemical assays of 3 molecules were merged, and analyzed, with a Ki67 labeling index of the same tumors. RESULTS: Cyclin D1 was expressed in 72 breast carcinomas (54.1%) and cyclin E in 60 (45.1%) out of the 133 breast carcinomas. Expressions of cyclin D1 and cyclin E were inversely related to each other, and significantly associated with the estrogen receptor (ER) expression and differentiation of the breast carcinoma. The expression of cyclin E was significantly decreased in tumors expressing cyclin D1 (p=0.022). There was a trend for cyclin D1 expression to increase in tumors expressing p27Kip1 (p=0.053), but the expression of cyclin E did not correlate with p27Kip1 expression. The Ki67 labeling index was markedly increased in tumors expressing cyclin E, whereas it was significantly decreased in the cyclin D1 or p27Kip1 expressing-tumors. From survival analysis, cyclin E expression was the only significant variable for the prediction of poor survival. CONCLUSION: The abnormal expressions of cell cycle regulatory molecules are prevalent, and interrelated with each other in breast cancer. Integration of TMA technology allowed a high-throughput analysis for correlating molecular the in situ findings, with the clinico-pathologic information. Among the three molecules studied, the cyclin E had a prognostic implication for stage I and II breast cancer.

Comparison of Tamoxifen and Toremifene as Adjuvant Treatment in Node-negative Postmenopausal Breast Cancer

PURPOSE: To evaluate the differences in therapeutic efficacy and toxicity profiles between adjuvant toremifene and tamoxifene in postmenopausal breast cancer patients. METHODS: Toremifene 40 mg (n=115) and tamoxifen 20 mg (n =116) were administered daily for more than 2 years after curative surgery for lymph node-negative breast cancer. Toxicity profiles were compared between the two groups and the patient survival rate was also analyzed. RESULTS: Sweating and hot flashes were the most common symptoms in the two groups (toremifene vs. tamoxifen= 47.8% vs. 49.1%). Increase of vaginal discharge (39.1% vs. 36.2%) and weight gain (21.7% vs. 24.1%) were the next following adverse effects. There was no significant difference in adverse effect between the two groups. During the median follow-up period of 25 months (range: 9~38 months), five (4.3%) and four (3.3%) patients treated by toremifene and tamoxifen, respectively, had recurrent disease. CONCLUSION: The clinical outcome and adverse effect profiles of toremifene were similar to those of tamoxifen. Toremifene at 40 mg/day seems to be as safe and effective as tamoxifen at 20 mg/day in the treatment of postmenopausal, node-negative, breast cancer. However, a longer follow-up study is needed to verify this.

Prognostic Factor of Congenital Esophageal Atresia

PURPOSE: This study was undertaken in order to analyze clinical data concerning cases of esophageal atresia cases we encountered to elucidate the risk factors that may more accurately predict a prognosis. METHODS: We retrospectively reviewed the medical charts of 19 infants with esophageal atresia diagnosed at Sanggye Paik Hospital from June 1991 to May 2000. RESULTS: The mean birth weight of the infants was 2.46 kg (0.97~3.99 kg). Associated anomalies occurred in 12 infants (63.2%), including cardiovascular anomalies in 10 (52.6%), anorectal anomaly in 1 (5.3%), renal anomaly in 1 (5.3%), skeletal anomaly in 1 (5.3%) and chromosomal anomaly in 1 (5.3%). We performed primary end-to-end anastomosis with one layer of interrupted suture in 12 infants. Primary repair was carried out in 7 infants, simultaneously with gastrostomy in 1, and gastrostomy & delayed end-to-end anastomosis was performed in 4. Postoperative complications included pneumonia in 8 (66.7%), leakage in 4 (33.3%), stricture in 4 (33.3%), sepsis in 2 (16.7%), wound infection in 1 (8.3%) and gastroesophageal reflux in 1 (8.3%). The postoperative mortality rate was 25.0% (3/12). Causes of death included sepsis (n=2) & heart failure (n=1). According to the Waterston criteria, 4 infants (21.1%) were classified as group A, 6 (31.6%) as group B, and 9 (47.3%) as group C. The postoperative survival rates of group A, B, and C were 100% (3/3), 80% (4/5), and 50% (2/4) respectively. The postoperative survival rates of class I and class II by Montreal classification were 88.9% (8/9) and 33.3% (1/3), respectively. CONCLUSION: Our data suggests that associated anomalies and general conditions are more important prognostic factors than birth weights in patients with esophageal atresia.

Safety and Effect of the Perigastric Devascularization with Transection of Esophagus for Treatment of Esophageal Varices

PURPOSE: There are a variety of approaches to the treatment of esophageal varix. This study evaluates the value of perigastric devascularization with transection of the esophagus, a non-shunt operation, for the management of bleeding esophageal varices. METHODS: We retrospectively analyzed the medical records of 16 patients with esophageal varix bleeding who had undergone perigastric devascularization with transection of the esophagus from 1990 through 2000. RESULTS: The mean age of the patients was 40.8 years and the most common underlying pathology was viral hepatitis. All patients had a history of previous variceal bleeding. Elective and prophylactic surgery was done in 8 and 5 patients respectively, and emergency surgery in 3 patients. One patient in Child group C and underwent emergency surgery, died after operation (mortality rate 6.3%). In the remaining 15 patients, two patients died of hepatocellular carcinoma. None of the patients demonstrated rebleeding or recurrence of the varix in the follow-up period. In 8 patients, the liver function, as measured by Child-Pugh classification, was improved following surgery as compared with measurements at the time of admission. CONCLUSION: According to this study, in spite of the small number of patients, we suggest that perigastric devascularization with transection of the esophagus is a very safe and effective treatment modality for esophageal varix bleeding, particularly if it can be done for an elective or prophylactic purpose. Furthermore, we propose that the operation should be carried out in an elective rather than in emergency manner following the improvement of liver function by non- invasive medical treatment.

Use of the Triple Test at the Breast Screening Center for Patients with Breast Mass

PURPOSE: Breast mass - the most common occurences in the breast must be managed by a method that provides both the best medical and cosmetic results. METHODS: Two hundred seventy-eight patients evaluated and managed for breast mass at our center between January 1998 and December 1999 were analysed. In this study, we compare the results of the triple test score (TTS; sum of physical examination, mammography, and fine needle aspiration cytology) with those from each separate diagnostic test according to a standard formula incorporating sensitivity, specificity, positive predictive value, and negative predictive value. The TTS was modified to substitute sonography for mammography-TTSs. The TTS was also compared to the TTS-2 that double weighted the results of fine needle aspiration (FNA), but was otherwise the same as the TTS. RESULTS: The sensitivity and specificity of breast sonography were 90% and 84% whereas those of mammography were 84% and 73%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the TTSm (triple test score-mammography) were 99%, 97%, 99% and 97% respectively. The scores of the TTSm-2 were 99%, 100%, 100% and 97%. And those of the TTSs were 100%, 100%, 100% and 100%. CONCLUSION: The TTS was more accurate than each of the elements separately in evaluating breast masses. The TTSs was also more effective than the TTSm. The TTS-2 was more useful than the TTS, being less likely to miss malignancy due to the high accuracy of FNA.

Expression of p27Kip1 Protein Associated with Poor Clinical Outcome in Human Gastric Cancer

PURPOSE: p27Kip1 protein is an inhibitor of cyclin-dependent kinases and is thought to be a potential prognostic indicator for numerous human cancers. We investigated the expression of p27Kip1 in gastric cancer in order to estimate its clinical utility. METHODS: Immunohistochemical assay for p27Kip1 protein was performed in 64 patients with primary gastric cancer. The correlation between p27Kip1 and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P=0.015) and was also reduced in tumors with a high S-phase fraction as compared with tumors showing a low S-phase fraction (86.7%, 26/30, 41.2%, 14/34; P=0.0002). In univariate analysis, the extent of the disease (P<0.001), and reduced expression of p27Kip1 (P=0.0006) were statistically significant to predict the patient's outcome, however depth of invasion (P=0.008) and pathologic stage (P=0.009) emerged as significant prognostic indicators in the multivariate analysis. CONCLUSION: The expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 appears to have potential as a prognostic marker in the management of gastric cancer patients.

Primary Experience with Oxaliplatin Chemotherapy for Recurrent and/or Metastatic Colorectal Cancer

PURPOSE: In the past 30 years, the chemotherapeutic approach to advanced colorectal cancer has remained major challenge. Fluorinated pyrimidine has been the main active drugs, and cisplatin was introduced under clinical conditions. Because of the renal and hematologic toxicity of cisplatin, oxaliplatin was developed. The purpose of this study was to assess the clinical response to and the side effects of oxaliplatin chemotherapy. METHODS: From January 1999, 11 patients who received oxaliplatin chemotherapy entered this study. There were 9 males and 2 females, and their ages varied from 40 to 71 years old. The mean ECOG scale was 1. According to TNM staging, 2 was stage 2 at diagnosis, 5 at stage 3, and 4 at stage 4. Totally, we performed 57 cycles of oxaliplatin chemotherapy. Labaratory data and toxicity were assessed for each cycle according to the WHO scale. Ten (10) patients have received follow-up CT since treatment. RESULTS: Grade 1 anemia occurred in 68% of the cycles, grade 2 in 20%, and grade 3 in 12%. Grade 1 thrombocytopenia occurred in 35% of the cycles and grade 2 in 14%. Grade 1 leukopenia and neutropenia occurred in 27% and 25% of the cycles, respectively. Grade 1 stomatitis occurred in 12% of the cycles and grade 2 in 2%. Grade 1 nausea occurred in 44% of the cycles. Grade 1 vomiting occurred in 14% of the cycles and grade 2 in 4%. Grade 1 diarrhea occurred in 10% of the cycles and grade 2 in 4%. Nephrotoxicity was absent, and typical oxaliplatin neurotoxicity was reported as grade 1 in 2% of the cycles. No complete response was observed, and oxaliplatin che motherapy induced one partial remission. CONCLUSION: There was a mild hematologic and alimentary side effect. There were no renal and few neurologic side effects, but the response to oxaliplatin was poor.

Myxoma of the Breast: A case report

A case of myxoma of the breast was reported. A 25-year-old woman showed a lump in the left breast which was suddenly enlarged after the delivery of a baby. A tumor measuring 73.53cm was located in the upper outer quadrant of the breast. Fine needle aspiration cytology revealed scattered benign spindle shaped mesenchymal cells with abundant myxoid material. On excision, the tumor was partly solid, partly cystic and multilocular. Each nodule consisted of an abundant mucoid material with a few spindle or stellate mesenchymal cells. Pleomorphism and mitosis were absent. The mesenchymal cells showed immunoreactivities for S-100 protein, smooth muscle actin, and CD34. The myxoid stroma was positively stained with alcian blue and mucicarmine. These findings suggest that constituent cells derive from totipotential primitive mesenchymal cells.