Leptin as a Potential Target for Estrogen Receptor-Positive Breast Cancer / 한국유방암학회지

PURPOSE: Leptin is a potent adipokine that plays a significant role in tumor development and the progression of breast cancer. The aim of this study was to evaluate whether leptin affects the response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancer cells. METHODS: Leptin, leptin receptor (Ob-R), and activation of signaling pathways were studied by Western immunoblotting. The effects of leptin on tamoxifen-dependent growth inhibition were studied in MCF-7 and T-47D cells. RESULTS: Leptin was expressed in MCF-7 and T-47D and had a proliferative effect on MCF-7 cells. Leptin significantly inhibited the antiestrogenic effect of tamoxifen in both cells only under beta-estradiol (E2) (20 nM) conditions. In MCF-7, the inhibitory effect against tamoxifen was a result from the activation of the ERK1/2 and STAT3 signal transduction pathway. CONCLUSION: Leptin interferes with the effects of tamoxifen under E2 stimulated conditions in ER-positive breast cancer cells. These results imply that inhibition of leptin is expected to enhance the response to tamoxifen in ER-positive breast cancer cells, and, therefore, could be a promising way to overcome endocrine resistance.

Factors Associated with Re-excision after Breast-Conserving Surgery for Early-Stage Breast Cancer / 한국유방암학회지

PURPOSE: Re-excisions after breast-conserving surgery (BCS) for breast cancer cause delays in the adjuvant treatment, increased morbidity, and leads to poor aesthetic results. Thus, efforts to reduce the re-excision rate are essential. This study aimed to conclusively determine the re-excision rate and the factors associated with re-excision after BCS. METHODS: We retrospectively reviewed the medical records and pathological reports of 711 cases that underwent BCS for early-stage breast cancer. Univariate and multivariate analyses were performed. RESULTS: Of the 711 cases of BCS, 71 (10.0%) required re-excision. Patients in the re-excision group were younger than those in the no re-excision group. Non-palpable lesions, the presence of non-mass-like enhancement at magnetic resonance imaging, multifocality, the presence of a ductal carcinoma in situ (DCIS) component, and an infiltrative tumor border were also significantly associated with re-excision. Multivariate analysis indicated that younger age, non-palpable lesions, multifocal lesions, and the presence of a DCIS component were factors which were independently associated with re-excision. Tumors located in the lower inner quadrant had a relatively high involved resection margin rate as well as a narrow resection margin width, especially at the superior and medial margins. Lateral margins showed a tendency toward a wider resection margin width. CONCLUSION: At our institution, the rate of re-excision was low despite the lack of an intraoperative frozen section. Patients with non-palpable or multifocal tumors, a DCIS component, or those who were younger than 50 years were more likely to require re-excision after BCS. These factors should be considered when planning surgical management of early-stage breast cancer. Positive resection margin rates and margin widths differed on a directional basis based on tumor location, and these differences were considerable.

Clinical Significance of Annexin A1 Expression in Breast Cancer / 한국유방암학회지

PURPOSE: The expression of Annexin A1 (ANXA1) is known to be reduced in human breast cancer; however, the role of ANXA1 expression in the development of breast cancer remains unclear. In this study, we determined the relationship between the expression features of ANXA1 and the prognostic factors of breast cancer. METHODS: Human breast tissues were obtained from patients specimens who had undergone breast surgery or core needle biopsies. The patterns of ANXA1 expression were analyzed by immunohistochemical staining in relation to histopathological diagnosis, clinical characteristics and outcomes. RESULTS: One hundred eighty-two cases were included and the mean age of the patients was 46.34 +/- 11.5 years. A significant loss of ANXA1 expression was noted in both ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal breast tissues (p<0.001) and benign breast diseases (p<0.001). There was a significant alteration in ANXA1 expression according to hormone receptor status (p<0.001), cancer intrinsic type (p<0.001), and nuclear grade (p=0.004) in invasive cancer. In a univariate analysis, ANXA1 positivity tended to be related with poor breast cancer-related survival (p=0.062); however, the same results was not realized in multivariate results (p=0.406). HER2 overexpression and TNM staging were significantly associated with relapse-free survivals (RFS) in the multivariate analysis (p=0.037, p=0.048, respectively). In particular, in node-positive patients (p=0.048), HER2 overexpressed patients (p=0.013), and non-triple negative breast cancer patients (p=0.002), ANXA1 overexpression was correlated with poor RFS. CONCLUSION: Although significant loss of ANXA1 expression was noted in breast cancer including DCIS and invasive carcinoma, in cases of invasive cancer, overexpression of ANXA1 was related to unfavorable prognostic factors. And these results imply that ANXA1 plays dualistic roles and is involved in variable mechanisms related to cancer development and progression.

The Change of Practice Patterns of the Hereditary Breast Cancer Management in Korea after the Korean Hereditary Breast Cancer Study / 한국유방암학회지

PURPOSE: The objective of this study was to evaluate the change in the practice patterns for managing hereditary breast and ovarian cancer (HBOC) among Korean physicians after the Korean Hereditary Breast Cancer (KOHBRA) study. METHODS: The first survey was performed from July to August 2007, at the initiation of the KOHBRA study, and the follow-up survey was conducted from July to December 2009. Members of the Korean Breast Cancer Society were invited to participate in the study by e-mail. The 2009 survey was conducted with a self-administered questionnaire concerning HBOC management and was identical to the previous questionnaire. RESULTS: According to the 2009 survey, most physicians (60.0%) tended to draw a pedigree (48.0% in 2007 survey). The rate of genetic test recommendations for patients at risk for HBOC was higher in the 2009 survey (84.0%) than that in the 2007 survey (64.0%). Physicians tended to select a BRCA genetic testing candidate more appropriately than in the previous survey (42.4% answered right in 2007 survey; 74.4% in 2009 survey). Fifteen of 25 participants (60.0%) provided genetic counseling before their patients underwent a genetic test, which was higher than that (40.0%) in the 2007 survey. According to the 2009 survey, half of the genetic counseling was being conducted by KOHBRA study research nurses; whereas most of the genetic counseling was conducted by physicians in 2007. CONCLUSION: The KOHBRA study has played an important role in the appropriate selection of candidates for genetic testing. However, more effort should be placed on improving the pre-test genetic counseling rate.

The Use of Absorbable Surgical Mesh after Partial Mastectomy for Improving the Cosmetic Outcome / 한국유방암학회지

PURPOSE: Partial mastectomy without immediate volume replacement can be associated with cosmetic failure. The aim of the present study was to assess cosmesis achieved in patients who underwent partial mastectomy and reconstruction using absorbable surgical mesh. METHODS: We used absorbable surgical mesh (Polyglactin 910, Vicryl(R)) to repair defects after performing partial mastectomy in 25 patients. Endoscopy-assisted partial mastectomy was performed with conservation of the whole skin of the breast and areola. A tailored fan-shape mesh was inserted into the postoperative defect. The cosmetic appearance was evaluated using a simplified five-grade for five-items scoring system at 3 and 6 months after the operation. RESULTS: An excellent or good cosmetic result was obtained in 82.6% of the patients (19/23) after 3 and 6 months, and no major complications were noted. CONCLUSION: This procedure can be easily performed by general surgeons. Insertion of an absorbable surgical mesh into the postoperative defect could be an effective modality for reconstructing a defect after breast surgery.

Metastasis of Non-Small Cell Lung Cancer to Ipsilateral Breast: A Case Report / 한국유방암학회지

Breast tissue is an unusual site for metastatic disease, particularly for non-small cell lung cancer (NSCLC). Aside from contralateral breast cancer, the most common tumors metastasizing to the breast are malignant melanoma and hematopoietic malignances. We recently experienced a case of a 49-year-old female patient with solitary metastasis of NSCLC to ipsilateral breast tissue. She was diagnosed as NSCLC of left lung and underwent left upper lobectomy in 2001. She was then treated with etoposide/cisplatin chemotherapy and radiation therapy. After 35 months, she was referred to our breast clinic because of a nodular opacity in the left breast revealed by screening breast ultrasound, which proved to be of pulmonary origin. She was treated by wide excision and with docetaxel/cisplatin chemotherapy. However, 37 months after breast surgery, a metastatic lesion developed in the same breast and she received modified radical mastectomy. We report this case with a review of the literature.

The Role and Significance of Preoperative Breast MRI in the Setting of Breast Cancer / 한국유방암학회지

PURPOSE: Accurate preoperative assessment of breast cancer is important to determine the extent of disease and the plan for surgery. The purpose of this study was to evaluate the efficacy of preoperative breast magnetic resonance imaging (MRI) in breast cancer patients. METHODS: Between January 2001 and October 2007, 457 consecutive patients who had undergone surgical treatment for breast cancer were retrospectively studied. We compared 303 patients from the non-preoperative MRI group (group A) to 154 patients from the preoperative MRI group (group B). The impact of preoperative MRI was evaluated for each patient with regard to changes in therapeutic intervention. RESULTS: MRI alone revealed 17 new lesions. The results of the MRI led to a change in 9.1% of the planned surgical procedures. Tumor size was more accurately defined in patients undergoing MRI than in those undergoing ultrasound imaging. CONCLUSION: Breast MRI could be recommended as a preoperative diagnostic procedure in patients allocated to receive breast conservation surgery, because MRI may reveal unsuspected multifocal or multicentric tumors or carcinoma infiltrations and may result in changes in therapy.

A Pig to Canine Auxiliary Hepatic Xenotransplantation Model: Prevention of Hyperacute Rejection via Blocking the Kupffer Cells and Regulating the Complement Family

PURPOSE: We designed a pig to canine liver xenotransplantation model to study the diverse immunologic and hemodynamic consequences that follow xenotransplantation and hyperacute rejection. METHODS: The animals were divided into two groups: the cobra venom factor and Gadolinium chloride treatment group (CVF+Gd group) (3 cases) and the control group (3 cases). The donor pig's whole liver was harvested, and then the harvested pig's whole liver was transplanted into a dog after the dog underwent left hepatectomy. After reperfusion of the graft, blood samples were taken 20, 40 and 60 minutes after reperfusion, and the liver, lung and kidney tissues were taken 1 hour after reperfusion. RESULTS: In the control group, the grafts showed a patchy hypoperfused liver surface and it felt rubbery solid compared to the CVF+Gd group. The serum total protein, albumin, fibrinogen and platelets decreased abruptly and there were no significant differences between the two groups. The serum PT, PTT and FDP were increased in both groups and the CVF+Gd group showed a more obtuse slope than the control group. We could not find any intravascular pathologic changes on the microscopic findings of the graft. Only scant intravascular fibrin deposition was found. Hepatocellular vacuolization and sinusoidal dilatation were also found. There were patches of necrosis without any zonal distribution, intrasinusoidal neutrophil sequestration and interstitial hemorrhage. These findings were milder in the CVF+Gd group. CONCLUSION: The pig to canine partial auxiliary liver xenotransplantation model is feasible and it is a good model before starting to perform pig to primate liver xenotransplantation. In the CVF+Gd group, pathologic findings like patch hepatocyte necrosis etc. were less severe. As there were no corresponding vascular pathologic findings, these findings are not the direct effect of CVF and gadolinium treatment, and so other factors like Ischemia- reperfusion injury should be considered.

The Usefulness of Endotoxin for Detection of Mucosal Injury in Intestinal Obstruction

PURPOSE: The treatment outcome of an intestinal obstruction depends on the early recognition and emergent operation of a strangulated intestinal obstruction. Endotoxin is a lipopolysaccharide component of the cell wall of gram negative bacteria that normally exist in the intestinal lumen. When a strangulated obstruction occurs, the endotoxin passes transluminally into the peritoneal cavity and blood stream. A disruption of the mucosal barrier is an important putative cause in this pathogenesis. This study investigated the relationship between the endotoxin level and progress of an intestinal obstruction to a strangulated obstruction. METHODS: 25 adult male Sprague-Dawley rats (200~250 g) were divided into 3 groups, the control group, simple obstruction group, and closed loop obstruction group. An intestinal obstruction was induced using a silk tie. Blood samples and obstructed bowel wall specimens were obtained at 24, 48 and 72 hours after surgery. The endotoxin and IL-6 levels were examined, and all specimens were reviewed by a pathologist for mucosal damage after H-E staining. RESULTS: In the obstruction groups, dilated bowel loops at the proximal end of the obstruction site was identified but there were no ischemic changes. The endotoxin and IL-6 levels were similar regardless of the obstruction types and times. There were no differences between the three groups in the degree of mucosal damage. However, according to the endotoxin level, the groups with an endotoxin level < 0.2 EU/ml showed mild mucosal damage. The severity of mucosal damage increased with increasing endotoxin level. CONCLUSION: There is a positive relationship (r(2)=0.673, P-value=0.002) between the endotoxin level and mucosal damage. This suggests the possibility of using endotoxin as a predictive factor for the detection of mucosal injury in an intestinal obstruction. However, a larger scale will be needed to confirm the statistical significance.

Toxicity of Concurrent Adjuvant CMF Chemotherapy and Radiotherapy in Patients with Early Breast Cancer / 한국유방암학회지

PURPOSE: Many patients with early stage breast cancer are currently being treated with both adjuvant chemotherapy (CT) and radiotherapy (RT). We performed this study to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5-fluourouracil (CMF) CT and RT for treating early breast cancer patients. METHODS: Between January 2000 and December 2005, 97 patients with stage I or II invasive breast carcinoma were treated with breast-conserving surgery, and they received 6 monthly cycles of classic oral chemotherapy with CMF. Within day 7 of cycle 1, the patients started 3 dimensional conformal RT (3DCRT) with a stadard dose, followed by a boost. We used the Common Terminology Criteria for Adverse Events v 3.0 to score the level of acute toxicity for CT. The adverse effects of RT were graded according to the Radiation Therapy Oncology Group criteria. RESULTS: The mean age of the patients was 45.8 yr (range:30-64). The most common toxicity was nausea and leukopenia. The dose of chemotherapy was reduced to 80% of the planned dose for 6.2% of the patient. CT was disrupted for 4.1% of the patients. RT was not disrupted for any patient. Grade 3 and 4 neutropenia occurred in 41 (42.3%) patients, but only one patient needed hospitalization due to fever. Grade 3 skin lesions developed during or shortly after RT in 10.7% of the patients. Radiation penumonitis was noted in 15.5% of the patients. The median follow-up time was 38 months. There was no local recurrence and 2 (2.08%) distant metastases during follow-up. CONCLUSION: From the results of our study, we conclude that the concurrent administration of adjuvant CMF CT and RT is associated with a low risk of serious toxicity and this is an acceptable adjuvant regimen for patients with early stage breast cancer.

The Effect of alpha-Melanocyte Stimulating Hormone on Renal Ischemia Reperfusion Injury / 대한이식학회지

PURPOSE: In ischemia-reperfusion induced renal injuries, cytokines, chemoattractant chemokines, adhesion molecules and nitric oxide play an important role. alpha-Melanocyte stimulating hormone (alpha-MSH) is a potent anti-inflammatory cytokine so the therapeutic effect of alpha-MSH on an ischemia-reperfusion induced acute renal failure is to be evaluated. METHODS: 40 male Spraque-Dawley rats were prepared for the experiment, they were classified into three classes (Sham, ischemic control and alpha-MSH injection). Both renal pedicles were clamped for 45 minutes. alpha-MSH (50 microgram) was injected intravenously three times, immediately before ischemia and reperfusion and 18 hour after reperfusion. Serum creatinine and histologic changes were analyzed between groups (Sham (n=6), ischemic control group (n=15), and alpha-MSH group (n=19)). RESULTS: Serum creatinine level decreased significantly at 24 hours after reperfusion in alpha-MSH treated animals (SCr24 0.78+/-0.23 mg/dL, 4.21+/-1.14 mg/dL, 3.01+/-1.19 mg/dL, repectively (P=0.008)), especially serum creatinine level at 48 hours after reperfusion much more dicreased in alpha-MSH group (SCr48 0.67+/-0.16 mg/dL, 4.21+/-2.03 mg/dL, 1.15+/-1.11 mg/dL, repectively (P=0.004)). Tubular neccrosis and neutrophil infiltration decreased signigicantly in alpha-MSH treated group (P=0.001). Mortality was noted 33.3% only at ischemic conrol group. CONCLUSION: we demonstrate the fact that alpha-MSH has protective role on ischemic renal injury and improves survival rates.

Efficacy and Safety of Rotating Pigtail Catheter: Lower Extremity Deep Vein Thrombosis of May-Thurner Syndrome

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of mechanical fragmentation of iliofemoral deep vein thromboses (DVT) with rotating pigtail catheter followed by aspiration thrombectomy. METHOD: Thirteen patients (nine females, four males, 59.9+/-21.37 years old) with iliofemoral DVT underwent treatment for thirteen affected limbs. About 5~10 min after infusing 400,000~700,000 IU urokinase into the thrombosed deep veins, thromboses were fragmented by the mechanical action of the rotating pigtail catheter tip. After fragmentation of the thromboses, we aspirated the fragmented thromboses. Stent insertion or balloon angioplasty was applied if iliac vein stenosis was demonstrated after the above procedure was completed. We evaluated the total procedure time, volume of thrombolytic agent (urokinase), valvular injury, symptom-free time interval and success rate (primary patency rate). RESULT: In all 13 patients, iliofemoral DVT was successfully fragmented and aspirated using a combination method of rotating pigtail catheter and aspiration thrombectomy (clinical and technical success rate, 100%). The thromboses were declotted by rotating pigtail catheter in an average time of 5.7 minutes. Average duration of the total intervention was 108 min. Mean primary patency was about 4 months and there was no recurrence. Total UK average dose was 890,000 IU. There was no major complication such as pulmonary embolism or cerebral hemorrhage while the thrombus-fragmentation procedure was performed using rotating pigtail catheter. CONCLUSION: The combination method of rotating pigtail catheter and aspiration thrombectomy for treatment of iliofemoral DVT achieved rapid, safe, and effective recanalization in all cases without complication. Therefore, this procedure is a potential option in patients presenting with iliofemoral vein thrombosis.

Chronological Changes of Surgical Strategy for Early Gastric Cancer: Our 10 Years' Experience

PURPOSE: To analysis the chronological changes of surgical strategy for early gastric cancer (EGC) in our hospital over a 10-year period. METHODS: From November 1993 to August 2003, we experienced 201 patients with EGC at Ewha Womans University Mokdong Hospital. The medical and pathologic records of these patients were reviewed retrospectively. The patients were categorized into three groups in chronological order: P1 (1993~1996), P2 (1997~2000), and P3 (2001~2003). The clinicopathological characteristics and treatment modalities among these three groups were compared. RESULTS: Of the 683 gastric cancer patients, 201 patients (29.7%) were pathologically confirmed to have EGC. The proportion of EGC gradually increased in chronological order: 19.2% in P1, 33.2% in P2 and 32.9% in P3. There were no significant differences in clinicopathological characteristics among three groups, including age, sex, location, size, gross type, histology, depth of invasion, and lymph node metastasis. Open surgery was performed in 134 patients, laparoscopic surgery in 52 and endoscopic mucosal resection (EMR) in 15. The proportion of minimally invasive surgery such as EMR, laparoscopic wedge resection, laparoscopy- assisted distal gastrectomy (LADG), and hand-assisted laparoscopic surgery (HALS) increased in chronological order: 0% in P1, 22.4% in P2 and 58.5% in P3. The postoperative mortality was 1.49% (3/201): 2 cases after open surgery, and 1 case after laparoscopic wedge resection. One case after open conventional surgery recurred. There were no significant difference in postoperative complication, postoperative mortality and survival rate among the three groups. Overall 5-year survival rate was 95.4%. CONCLUSION: The proportion of minimally invasive surgery increased during a 10-year period in our hospital. However, there were no significant differences in postoperative complication, postoperative mortality, recurrence rate, and survival rate among three chronological groups.