PURPOSE: Most tests developed for the determination of the HER2 status still require validation, although identification of the HER2 status is important for predicting the response to specific systemic therapy in breast cancer. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed for the HER2 expression on the tissue microarray (TMA) from primary breast cancers to validate the feasibility of IHC for HER2 assay. METHODS: A TMA was constructed from 134~231 primary breast cancers. FISH and IHC were repeated more than twice, and the results were analyzed. Three kinds of primary antibody for IHC were used and compared. RESULTS: The HER2 was amplified by FISH in 24~28% of breast cancer with a concordance between multiple assays of 92~100% (kappa=0.994-0.965), while the HER2 was overexpressed in 21~27% by IHC. The HER2 was amplified in 70~100% of the IHC 3+ cases, but was observed in only 45~78% and 5~12% of the IHC 2+ and IHC 0~1+ cases, respectively. The results from the IHC, using 3 different primary antibodies to HER2, were in good agreement each other at 88~92% (kappa=0.902-0.799). CONCLUSION: The results of the FISH appeared to be more reproducible than those of the IHC in the current study. The results of the IHC were not different from each other according to primary antibody used. However, a considerable proportions of the IHC positive cases were not confirmed by the FISH. This report indicates a need to improve the laboratory quality control measures when using the IHC for the HER2 assay, including the periodic testing for the concordance with FISH.
Antibodies ; Breast Neoplasms* ; Breast* ; Fluorescence* ; Immunohistochemistry* ; In Situ Hybridization* ; Quality Control

PURPOSE: Biologic characteristics of the tumors could be altered after chemotherapy. Accurate assessment of tumor biology before treatment is important for selecting treatment modalities. Current study was designed to investigate whether multiple molecular markers could be accurately assayed on the fine needle aspirates from the breast carcinoma. METHODS: Immunocytochemical assays (ICA) for p53, cyclin D1, and cathepsin D were performed on cytologic samples from 76 primary breast carcinomas, 37 ductal carcinoma in situ (DCIS), and 36 benign ductal hyperplasia. ICA for 3 molecules was also performed on the histologic sections from the matching tumor blocks, and the results were compared. RESULTS: Three molecular markers were successfully detected in cytologic samples from the breast carcinomas; p53 in 71.1% (54/76), cyclin D1 in 73.7% (56/76), and cathepsin D in 44.7% (34/76). Their expression was rarely observed in benign hyperplasia; p53 in 0/36, cyclin D1 in 7/36, and cathepsin D in 4/36. Increase of expression frequency of 3 molecules was apparent through the progress of the disease. Results of ICA for each molecules were well correlated between cytologic and histologic samples; concordance was 93.4% (71/76) for p53, 81.6% (62/76) for cyclin D1, and 73.7% (56/76) for cathepsin D. When 3 molecular markers were integrated to the preoperative diagnosis, positive predictive value was 90.6% for malignant breast disease. CONCLUSION: Three molecular markers were successfully assayed on cytologic samples and well correlated with the results from the histologic sections. The results indicate that the biologic information from the fine needle aspirates can be reliably integrated to patients treatment.
Biology ; Breast Diseases ; Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Cathepsin D* ; Cathepsins* ; Cyclin D1* ; Cyclins* ; Diagnosis ; Drug Therapy ; Humans ; Hyperplasia ; Needles ; Population Characteristics

Breast conserving surgery is increasingly performed in early stage breast cancer patients. A certain propotion of these patients are at substantial risk for systemic metastasis. However, there is no valid consensus about optimal sequencing of chemotherapy and radiation therapy. We conducted a randomized prospective study to investigate whether concurrent chemotherapy and radiation therapy after breast conservation surgery are associated with increased toxicity. Fifty-seven patients with stage I or II breast cancer were randomly assigned to receive CMF chemotherapy either simultaneously (n=37) or before (n=20) radiation therapy. Moist desquamation was the most common adverse effect which occurred in 46% (16/37) treated with concurrent chemotherapy and radiation therapy while 8 patients (38%) treated with sequential regimen had the finding. Difference between two groups was not statistically significant. Incidence of severe neutropenia (WBC>1,800) or abnormal elevation of liver enzymes was also not influenced by sequencing of adjuvant therapies. Arm edema was observed in 2 patients of concurrent group and was observed in 2 patients treated with sequential regimen. Two patients treated with concurrent regimen did not complete 6 cycles of chemotherapy while one patient with sequential regimen did not complete. Incidence of toxicity during chemotherapy was not altered by timing of radiation therapy. In conclusion, chemotherapy and radiation therapy can be given concurrently after breast conservation surgery in stage I or II breast cancer patients without increase of serious toxicity.
Arm ; Breast Neoplasms* ; Breast* ; Consensus ; Drug Therapy* ; Edema ; Humans ; Incidence ; Liver ; Mastectomy, Segmental ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies

Solid and papillary epithelial neoplasm of the pancreas(SPENP) is an uncommon low grade malignant tumor histologically distinct from the usual ductal adenocarcinoma and amenable to cure by surgical excision. The main features of SPENP are a peculiar morphology, favorable prognosis, and prediction for women 10 and 40 years of age. In men, the occurrence of SPENP seems to be exceedingly rare. The tumor is usually large at the time of presentation, and surgical excision is the treatment of choice. Gross pathologic examination revealed apparent encapsulation, cystic degeneration, and hemorrhagic necrosis. Microscopically, the tumor was characterized by distinctive solid and papillary patterns. This benign or low-grade malignant epithelial tumor is composed of monomorphous cells variably expressing epithelial, mesenchymal, and endocrine markers. The tumor is known to have good prognosis; although local invasion and infiltration of the capsule may occur. Despite growing recognition of this tumor, its histogenesis remains a matter of controversy i.e. pancreatic ductal cell origin, acinar cell origin, pluripotential cell origin. A 44-year-old male presented with an one-year history of postprandial abdominal pain. Following abdominal ultrasonography, computed axial tomography and angiography, a SPENP suspected. The patient underwent exploratory laparotomy. The tumor was located in the head of pancreas. And thus the patient underwent a pylorus-preserving pancreaticoduodenectomy. His postoperative course was uneventful, and he remains well.
Abdominal Pain ; Acinar Cells ; Adenocarcinoma ; Adult* ; Angiography ; Carcinoma ; Female ; Head ; Humans ; Laparotomy ; Male* ; Necrosis ; Neoplasms, Glandular and Epithelial* ; Pancreas* ; Pancreatic Ducts ; Pancreaticoduodenectomy ; Prognosis ; Ultrasonography

PURPOSE: Incidental parathyroidectomy is the most common and unexpected consequence of a total thyroidectomy. It can cause hypocalcemia symptoms such as muscle cramping and even seizures. We conducted this study to compare several factors including the preservation rate of parathyroid glands during both a bilateral axillo-breast approach endoscopic thyroidectomy (BABA) and a conventional open thyroidectomy (CT) for papillary thyroid carcinomas. METHODS: We retrospectively reviewed the medical records of 299 papillary thyroid cancer patients who had a total thyroidectomy between January 2008 and December 2011. We grouped the patients into two groups: BABA (n=70) and CT (n=229). We analyzed age, tumor size, operation time, the number of preserved and removed parathyroid glands, amount and duration of seroma drainage, pain score, hypocalcemia symptoms, and serum total calcium level in both the BABA and CT groups. RESULTS: We observed a younger age (under 45 years old) (P=0.000), smaller tumor size (P=0.000), longer operation time (P=0.000), larger amount of drainage (P=0.000), longer duration of drainage (P=0.007), and larger pain score (P=0.000) in the BABA group. Of the 70 patients that received an endoscopic thyroidectomy, we preserved all four parathyroid glands in 56 patients (78.6%). Of the 229 patients that received an open thyroidectomy, we preserved all four parathyroid glands in 141 patients (61.6%, P=0.004). CONCLUSION: BABA results in more extensive tissue damage over a longer period of time than CT. However, BABA was an excellent method for preserving parathyroid glands when compared with CT for thyroid carcinoma. Thus, it seems to be feasible performing BABA when it matches the indications.
Calcium ; Drainage ; Humans ; Hypocalcemia ; Hypoparathyroidism ; Medical Records ; Methods ; Muscle Cramp ; Parathyroid Glands* ; Parathyroidectomy ; Retrospective Studies ; Seizures ; Seroma ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy*

Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) uptake is known to be increased in breast cancer because of increased blood flow from angiogenesis and heightened metabolism. We performed a 99mTc-MIBI scan in a patient with mammary Paget's disease. The patient had underlying invasive cancer in the same side of the breast. 99mTc-MIBI scan exhibited a scintigraphic image of the uptake from the invasive cancer lesion located deeply in the breast toward the epidermis. 99mTc-MIBI showed an uptake in the deeply located invasive cancer lesion as well as nipple lesion. Especially, the delayed phase of Tc-MIBI scan demonstrated the tumor site more accurately. In conclusion, 99mTc-MIBI scan could be a useful adjunct to clinical decision making in the management of Paget's disease of the breast.
Breast Neoplasms/radionuclide imaging* ; Breast Neoplasms/pathology ; Case Report ; Female ; Human ; Middle Age ; Nipples/pathology ; Paget's Disease, Mammary/radionuclide imaging* ; Paget's Disease, Mammary/pathology ; Skin/pathology ; Technetium Tc 99m Sestamibi/diagnostic use*

PURPOSE: The purposes our study was to find out any histologic factors associated with negative conversion of axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC). We also evaluated the association between the decrease in size of primary breast tumor and negative conversion of ALN. METHODS: From January 2012 to November 2014, we included 133 breast cancer patients who underwent NAC and who had ALN metastases which were confirmed on fine-needle aspiration or core needle biopsy at initial diagnosis. All 133 patients underwent initial magnetic resonance imaging (MRI) at the time of diagnosis and preoperative MRI after completion of NAC. We measured the longest dimension of primary breast cancer on MRI. RESULTS: Of 133 patients, 39 patients (29%) showed negative conversion of ALN and of these 39 patients, 25 patients (64%) showed pathologic complete remission of primary breast. On univariate analysis, mean percent decrease in longest dimension, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status and histologic grade were significantly associated with the ALN status after NAC (p<0.001, p=0.001, p< 0.001, p=0.001, p=0.002, respectively). On multivariate logistic regression analysis, percent decrease in longest dimension (odds ratio, 1.026; 95% confidence interval [CI], 1.009-1.044) and histologic grade (odds ratio, 3.964; 95% CI, 1.151-13.657) were identified as being independently associated with the ALN status after NAC. The area under the receiver operating characteristic curve was 0.835 with the best cutoff value of 80% decrease in longest dimension. Combination of high histologic grade and more than 80% decrease in longest dimension showed 64% sensitivity and 92% specificity. CONCLUSION: High histologic grade and more than 80% decrease in primary tumor dimension were associated with negative conversion of ALN after NAC.
Biopsy, Fine-Needle ; Biopsy, Large-Core Needle ; Breast Neoplasms* ; Breast* ; Diagnosis ; Drug Therapy* ; Estrogens ; Humans ; Logistic Models ; Lymph Nodes* ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; ROC Curve ; Sensitivity and Specificity

PURPOSE: The optimal sequence of chemotherapy (CT) and radiotherapy (RT) remains uncertain although both can reduce breast cancer recurrence after breast-conserving surgery (BCS). The current study was performed to evaluate whether concurrent RT with CT increases chemotherapy-associated toxicities. METHODS: Two hundred and thirty-eight patients with stage I and II breast cancers were prospectively allocated concurrent CT and RT (N=133) or sequential CT and RT (N= 105) after BCS. In the sequential group, the RT was started after completion of 3 cycles of CT with an additional 3 cycles of CT delivered after the RT. All patients underwent intravenous CMF chemotherapy composed of cyclophosphamide (500 mg/m2), methotrexate (50 mg/m2) and 5-FU (500 mg/ m2), every 3 weeks for 6 cycles following surgery. RESULTS: There were no significant differences between the two groups with regard to the grade 3 or 4 hematologic toxicities during chemotherapy or in abnormal liver enzyme elevation. Radiation related adverse effects, such as moist desquamation and pneumonitis symptom, were no different between the two groups. During the median 42 month follow-up period, range 16- to 60 months, 18 (13.5%) and 20 (19.1%) patients in the concurrent and sequential groups had systemic recurrences of breast cancer. The disease-free survival and local recurrence rates were no different between the two groups. CONCLUSION: Concurrent CT and RT were not associated with an increased toxicity and reasonable cosmetic results were achieved in this current study. The current study indicates that concurrent RT with CT after BCS is a feasible treatment modality, with the advantage of a shortening treatment time.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant* ; Cyclophosphamide ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Follow-Up Studies ; Humans ; Liver ; Mastectomy, Segmental* ; Methotrexate ; Pneumonia ; Prospective Studies ; Radiotherapy* ; Recurrence

BACKGROUND: Periampullary cancer is a relatively common malignancy, and its incidence is increasing. Prognosis in these patients depends upon resection of the tumor because surgery is the only effective treatment for irradicating the disease. There has, therefore, been a renewed interest in the role of serological markers early diagnostic tools for periampullary cancer. The potential role of serological markers is not limited only to early detection, but may also be of assistance in the difficult clinical dilemma of differentiating periampullary cancer from other diseases. Furthermore, serological markers of periampullary cancer might be used in follow-up patients after treatment, particularly after surgical resection, in order to select those with minimal disease likely to respond better to adjuvant treatment and/or radiotherapy. METHODS: From March 1989 to May 1997, 54 patients were admitted to Sanggye Paik Hospital, InJe University, and had pathologically confirmed periampullary cancer. Of those, 28 patients underwent a biliary bypass or a drainage procedure [Group I], and the others received resection procedures (Whipple's operation or pylorus-preserving pancreatoduodenectomy)[Group II]. Preoperative and postoperative serum levels of bilirubin, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9(CA19-9) were measured in all patients. We evaluated the relation of the postoperative increase or decrease in those tumor markers to survival, and we discuss the usefulness of those markers as prognostic indicators in periampullary cancer. In this study, we focused on the changes in the CEA and the CA19-9 levels as function of the serum bilirubin concentration change. RESULTS: The bilirubin, CEA, and CA19-9 concentrations decreased significantly in Groups I and II after operation. The correlation between the decreases of the bilirubin and the CEA levels was statistically significant, but that between the bilirubin and CA19-9 had no statistical significance, in spite of the fact that the preoperative and the postoperative tumor marker concentrations had changed markedly. The reason for the statistical insignificance of the CA19-9 result may be the its relatively small sample size and the wide standard variation. The overall median and mean survival time of Group I were 4 months and 11 months, respectively, and those of Group II were 17 months and 21 months. CONCLUSION: We found that the serum the CEA and the CA19-9 levels could be used as a useful prognostic indicator change according to the serum bilirubin concentration even after a biliary drainage procedure and a biliary bypass. We conclude that various biliary bypass and drainage procedures can be effective treatments in periampullary cancer. However, because it is thought that many tumor markers are greatly affected by hyperbilirubinemia, liver dysfunction or cholestasis, further studies of the exact mechanism for the decrease or the increase in the tumor marker level as a function of the serum bilirubin concentration are mandatory. Precise information obtained by using multivariate analysis of large samples is essential for more accurate evaluation.
Biomarkers, Tumor ; Bilirubin* ; Carcinoembryonic Antigen ; Cholestasis ; Drainage* ; Humans ; Hyperbilirubinemia ; Incidence ; Liver Diseases ; Multivariate Analysis ; Pancreaticoduodenectomy* ; Prognosis ; Pylorus* ; Radiotherapy ; Sample Size ; Survival Rate

BACKGROUND: Periampullary cancer is a relatively common malignancy, and its incidence is increasing. A pancreaticoduodenectomy is the procedure of choice in patients with periampullary cancer. However, leakage of the pancreaticojejunal anastomosis has been a major complication after a pancreaticoduodenectomy, with a frequently reported incidence of 5 percent to 25 percent. The ideal management of the pancreatic stump has not yet been determined. Thus we tried to find a safe and effective pancreatic stump management technique and to monitor the security of the pancreatic stump anastomosis by using the body fluid amylase level. PATIENTS AND METHODS: Forty six (46) consecutive patients who had undergone a pancreaticoduodenectomy, between January 1990 and January 1998, were evaluated retrospectively. Before June 1997, we did 36 pancreaticojejunostomies without long stent insertion into the pancreatic duct (group 2). After that, we did 10 P-Jstomies with long stent insertion (group 1). A long silicone stent was used for intubation of the anastomosis. Also the amount of pancreatic juice drainage from the long pancreatic duct tube was checked daily. We placed two Penrose drains and one Jackson-Pratt drain near the anastomosis. Patients were monitored for clinical evidence of a pancreatic fistula by evaluation of the amylase concentration in serum and the peritoneal drainage at postoperative day 7. The normal range of body fluid amylase was defined to be within five times of the normal serum amylase level. Cholangiography, which was obtained through a T-tube or a percutaneous transhepatic catheter, was performed on postoperative day 7 and was used to assess to leakage from or the obstruction at any of the three reconstructive anastomoses. RESULTS: In group 1, there was no leakage from the P-Jstomy site. The daily mean pancreatic juice amount and body fluid amylase level were 76.6 ml/day (range, 0.4-137.4 ml/day) and 147.4 U/L (range,44-323 U/L). In group 2, there were 4 cases of leakage at the P-Jstomy site (11.1%). CONCLUSION: An external long pancreatic duct stent insertion is an effective and safe method for management of a pancreatic remnant. We could check the amount of the daily pancreatic juice precisely. Effective decompression of the P-Jstomy was achieved by long stent insertion. We could monitor the security of the pancreatic stump anastomosis by the body fluid amylase level. We suggest that our method, which monitors the body fluid amylase level, is effective in early detection and treatment of P-Jstomy site leakage. The effort to find the best method for management of the pancreatic remnant should be continued.
Amylases ; Body Fluids ; Catheters ; Cholangiography ; Decompression ; Drainage ; Humans ; Incidence ; Intubation ; Pancreatic Ducts* ; Pancreatic Fistula ; Pancreatic Juice ; Pancreaticoduodenectomy ; Pancreaticojejunostomy* ; Reference Values ; Retrospective Studies ; Silicones ; Stents*