A case of giant nipple adenoma.

BACKGROUND: Nipple adenoma is a relatively rare benign disease. Clinically, it often presents with nipple erosions, and it should be differentiated from Paget's disease. CASE PRESENTATION: The patient was a 63-year-old woman who complained of a lump in her left nipple for more than 30 years. Computed tomography performed for screening congestive heart failure suggested a left nipple mass of 40 mm in size. Needle biopsy revealed nipple adenoma, and skin biopsy was also performed to confirm the diagnosis. Nipple tumor resection was performed under local anesthesia, and we confirmed that the final diagnosis was nipple adenoma with negative margins. The patient has been free from recurrence for 2 years since the surgery. CONCLUSIONS: We have reported our experience of a case of giant nipple adenoma.

Combination of DYRK2 and TERT Expression Is a Powerful Predictive Marker for Early-stage Breast Cancer Recurrence.

BACKGROUND/AIM: DYRK2 is a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase induces degradation of telomerase reverse transcriptase (TERT). The expression of both proteins in breast cancer were investigated as predictors of recurrence. PATIENTS AND METHODS: Two hundred and twenty-one patients with early breast cancer treated at our institute between 2000 and 2009, were included. We used immunohistochemical analyses to measure the expression of DYRK2 and TERT and correlated it with clinicopathological factors and survival. RESULTS: DYRK2 and TERT were positive in 58 (26%) and 86 (39%) of 221 patients, respectively. There was no correlation between DYRK2 and TERT expression and clinicopathological factors. Better disease-free survival was observed in the DYRK2-positive group (p=0.032), and poorer disease-free survival was noted in the TERT-positive group (p=0.023). The DYRK2-positive TERT-negative group exhibited significantly better disease-free survival than the other groups (p=0.006). CONCLUSION: The combination of DYRK2 and TERT may be a powerful tool to stratify breast cancer patients.

[Paclitaxel plus Bevacizumab Therapy plus Surgical Resection Results in Local Control of Stage â ¢C Breast Cancer].

The case was a 40-year-old female who was aware of a right breast mass for 1 year before her first visit. She had visited her previous doctor because the mass was gradually increasing in size. After close examination, she was diagnosed with Stage ⅢC triple-negative breast cancer. She underwent 4 courses of EC therapy and 7 courses of paclitaxel(PTX)plus bevacizumab( Bev)therapy and was then, referred to our hospital for resection. We instituted a 2-month break from Bev to prevent postoperative complications. She underwent a right mastectomy, combined chest wall resection, lymph node dissection, and chest wall reconstruction. Because the postoperative course was good and quality of life improved, the multidisciplinary treatment with surgery and pharmacotherapy was considered effective in locally advanced breast cancer.

[Comparison of the Incidence of Febrile Neutropenia in Doxorubicin/Cyclophosphamide(AC)and Docetaxel/Cyclophosphamide(TC) Perioperative Chemotherapies for Primary Breast Cancer].

Febrile neutropenia(FN)is an adverse event associated with chemotherapy. Because well-maintained dose intensity improves survival rate, suppression of FN is important. While the incidence of FN has been recognized to be higher with docetaxel/cyclophosphamide(TC)therapy, it is generally considered lower with doxorubicin/cyclophosphamide(AC)therapy, and primary prophylaxis with granulocyte-colony stimulating factor(G-CSF)is not recommended. FN with AC therapy is commonly experienced in our daily practice. Thus, we retrospectively compared the incidence of FN with AC and TC therapies. We examined the data of 48 patients with primary breast cancer, consisting of 26 patients treated with AC and 22 patients with TC as perioperative chemotherapy-from January 2014 to September 2018-to determine the incidence of FN. FN was observed in 7/26 patients who received AC(26.9%)and 5/22 patients who received TC(22.7%). Excluding patients with primary prophylaxis with G-CSF, FN was observed in 7/23 patients(30.4%)who received AC and 5/18 (27.8%)who received TC. The incidence of FN with AC therapy was higher than that with TC therapy in this study. Therefore, positive use of G-CSF is necessary for safety and to adequately maintain dose intensity for AC therapy.

Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation.

Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

[Effect of weekly paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide as neoadjuvant treatment for patients with triple-negative and luminal-type breast cancer - a multicenter study].

This study examined the pathological complete response (pCR )rate and safety of induction chemotherapy with 12 cycles of weekly paclitaxel (80 mg/m²) followed by 4 cycles of 5-fluorouracil (500 mg/m²), epirubicin (100 mg/m²), and cyclo- phosphamide (500 mg/m²). The study medication was administered to female patients (n=31)with a mean age of 51 years, diagnosed with stage II A (n=18), II B (n=11) and III A (n=2) disease and with an estrogen receptor positive rate of 65% (20/31). No patient was HER2-IHC [human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)](3+) or HER2-FISH (fluorescence in situ hybridization) positive. Twenty-eight patients completed the treatment regimen. Treatment was halted in 2/31 patients due to progression of disease in one patient and a Grade 3 non-hematological adverse effect of skin eruption and itching in the other patient. A third patient died of causes unrelated to the study medication. Central review ascertained a pCR in 6 patients. In patients with triple-negative disease we observed a pCR rate of 67% (6/9). In patients with the Luminal (A+B) subtype, 0% (0/19) had a pCR. Grade 3/4 toxicity included leucopenia (58%), neutropenia (58%), febrile neutropenia (26%), fatigue (10%), and ALT elevation (7%). In terms of pCR, patients presenting with triple-negative disease and manageable safety profiles appear to respond well to this treatment regimen, while only a modest response was observed in patients with Luminal subtype disease.

Downregulation of DYRK2 can be a predictor of recurrence in early stage breast cancer.

This study investigated the potential of DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase gene, to predict disease-free survival for patients with early stage breast cancer. Two hundred and seventy-four patients with breast cancer underwent surgery from January 2000 to December 2009. All patients were in stage I or II. Immunohistochemical (IHC) analysis was used to determine the expression of DYRK2, which was examined for its association with clinicopathological factors or prognosis. A total of 85 of 274 cases (31%) were DYRK2 positive. No correlation was found between DYRK2 expression by IHC and clinicopathological factors such as tumor size, histological grade, hormone receptor status, and HER2 status; however, lymph node involvement was closely associated with DYRK2 expression. Ten-year disease-free survival in the DYRK2-positive group without node metastasis (95.9%) was significantly better than that in the DYRK2-negative group (87.3%, p = 0.015). These data show that DYRK2 expression is associated with lymph node involvement and is a possible predictive factor of breast cancer recurrence.

Totally thoracoscopic surgery and troubleshooting for bleeding in non-small cell lung cancer.

BACKGROUND: Although accumulating data support the feasibility and efficacy of video-assisted thoracic surgery anatomic resection, few studies have reported on intraoperative complications, such as vessel injury. The purpose of this study was to evaluate intraoperative vessel injury and to analyze troubleshooting. METHODS: Twenty-six of 557 patients with non-small cell lung cancer who underwent thoracoscopic anatomic lung resection were identified as having intraoperative vessel injury between January 2004 and December 2011. The injured portion, devices used, recovery approach, and hemostatic procedure were analyzed. The perioperative outcomes in patients with and without vessel injury were compared. RESULTS: The most commonly used devices were ultrasonic coagulation shears in 9 cases, followed by scissors in 5 and an endostapler in 4. Seventeen of the 26 cases were injured at the branches of the pulmonary artery, and the others were at major vessels. Half of the patients were converted to thoracotomy, and 6 were treated by minithoracotomy. Hemostatic procedures were primary closure in 17 and sealant in 7. The perioperative outcomes, including operative time and blood loss, were significantly different between the two groups, but duration of chest tube drainage, length of hospital stay, and morbidity rate were not. No mortality was identified in the patients with vessel injury. CONCLUSIONS: Video-assisted thoracic surgery anatomic resection was feasible and safe, regardless of the intraoperative vessel injury. Although surgeons should pay attention to avoid unexpected bleeding, the magnitude of injury and effectual step-by-step management should lead to a safe operation.

Image and pathological changes after radiofrequency ablation of invasive breast cancer: a pilot study of nonsurgical therapy of early breast cancer.

BACKGROUND: The surgical treatment of early breast cancer has proceeded to less invasive approaches with better cosmetic results. The current study was undertaken to evaluate the clinical and pathological findings after radiofrequency ablation (RFA) without resection for a longer period of time. METHOD: A total of 14 patients with breast cancer were enrolled. All patients were diagnosed to have invasive ductal carcinoma, and the median breast tumor size was 12 mm (range, 6-20 mm). Six patients received RFA treatment followed by immediate resection and eight patients without resection. The patients without resection were evaluated by ultrasound, MRI, and the pathological findings of a core needle biopsy after RFA. The removed specimens were examined by hematoxylin-eosin (HE) staining and nicotinamide adenine dinucleotide (NADH) diaphorase staining. The median follow-up of the patients was 39.9 months. RESULTS: NADH staining was necessary to diagnose complete tumor cell death in the tissue for 3 months after RFA. However, HE staining alone could confirm the effect without NADH staining more than 6 months after RFA. Post-RFA, MRI scans clearly demonstrated the area as a complete ablated lesion in all patients without resection. The ablated area detected by MRI or ultrasound became gradually smaller. All patients that underwent RFA with no resection were alive without relapse. CONCLUSION: RFA therefore could be an effective alternative to partial mastectomy for early breast cancer. Further research will be necessary to establish the standardization of the indications, as well as the optimal techniques and post treatment evaluation modalities.

Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression.

The human epididymis 4 (HE4) protein is expressed in the epididymis and respiratory tract. We previously reported that HE4 is also expressed in pulmonary adenocarcinoma. The purpose of this study was to investigate serum levels of HE4 as a biological marker in pulmonary adenocarcinoma. As the trained set, 102 patients with pulmonary adenocarcinoma who underwent surgery in our institute from 2008 to 2011 were evaluated. They were compared with 58 healthy controls and 16 cases of benign lung disease. In the validation, we used 104 patients with pulmonary adenocarcinoma operated on between 2000 and 2007. Postoperative changes of serum HE4 levels were investigated in 35 patients. The level of HE4 was determined by enzyme immunometric assay and compared with clinicopathological factors. In the trained set, HE4 levels in sera in pulmonary adenocarcinoma were significantly higher than in healthy controls and benign lung disease. Receiver operating characteristic curve showed that HE4 was a good discriminator of pulmonary adenocarcinoma (cut-off point, 50.3 pM; area under curve, 0.825; 95 % confidence interval, 0.76-0.89, p < 0.001). In the validation set, serum HE4 levels were significantly correlated with age, nodal status, and carcinoembryonic antigen. Furthermore, postoperative increase of HE4 serum levels showed a significant correlation with recurrence (p = 0.032). The 5-year overall survival rate was 52.6 % in the HE4-positive group compared with 97.1 % in the HE4-negative group (p = 0.001). These data showed that HE4 expression in sera is associated with progression of pulmonary adenocarcinoma and a possible biomarker.

[Surgical management for lung cancer in less than 1 cm].

Recently, the greater utilization of computed tomography (CT) has led to an increasing proportion of small-sized stage I A lung cancer in less than 1 cm in diameter. However, a treatment strategy for these small-sized lung cancers has not yet been defined. The aim of this study was to investigate surgical outcomes regarding these lung cancers. A total of 123 patients who underwent complete surgical resection for lung cancer in less than 1 cm between January 1995 and March 2010 were retrospectively evaluated. The 123 study subjects consisted of 54 male and 69 female patients. The mean age was 64.0 (43~82) years. The mean tumor size was 0.9( 0.3~1.0) cm. In this study, 70 patients underwent lobectomy (56.9%). Segmentectomy and wedge resection were underwent 23( 18.7%) and 30 patients( 24.4%), respectively. The 3-, 5- and 10-year survival rates were 95.7, 92.3 and 85.7%, respectively, after the operation for lung cancer in less than 1 cm. There were no significant difference between sublobar resection and lobectomy. However, 2 patients( 1.6%) had recurrent cancer and 7 patients (5.7%) had lymph node metastasis. We suggested surgical procedure for patients with lung cancers in less than 1 cm should be selected with the greatest care, because recurrent cancer and lymph node metastasis can occur in patients.

Does pneumothorax occurrence correlate with a change in the weather?

PURPOSE: There has been speculation that weather changes correlate with the incidence of spontaneous pneumothorax, although this has not been verified. Moreover, there are no significant data available on the meteoropathic pneumothorax in Asia. The aim of this study was to investigate the possible correlation and to compare our results to those of the United States and Europe. METHODS: From January 2000 to December 2009, 317 spontaneous pneumothorax cases with clear dates of onset were treated in our institution. Using the meteorological data of Fukuoka, Japan, the days with and without an occurrence of pneumothorax were statistically compared in terms of atmospheric pressure, the amount of precipitation, temperature, humidity, hours of sunshine, and occurrence of a typhoon and lightning. RESULTS: Multivariate analysis revealed that a decrease in the hours of sunshine, an increase in mean temperatures 2 days before the incidence, and the days following a day with lightning were all significantly correlated with the occurrence of pneumothorax (P = 0.2 days before the incidence, and the days following a day with lightning were all significantly correlated with the occurrence of pneumothorax (P = 0.0083, 0.0032, 0.0351, respectively). However, typhoons, as an "unusual" weather condition, did not influence the incidence of pneumothorax (P = 0.983). CONCLUSIONS: Our results show strong similarities with reports from European countries despite the different climates. We conclude that the occurrence of pneumothorax appears to correlate with some weather conditions in Japan.

Tracheal resection for malignant and benign diseases: surgical results and perioperative considerations.

PURPOSE: Tracheal surgery is an established treatment for various diseases; however, it is still a potentially challenging procedure. We herein discuss the safety of this procedure with regard to the coordination with airway interventional and anesthetic support. METHODS: A tracheal resection was performed on 18 patients. The dyspnea due to pre-existing severe airway stenosis, which was considered to be a risk factor for the safe induction of general anesthesia, was present in 12 (66.7%) cases. RESULTS: Seven of the 12 patients with pre-existing airway obstruction required interventional airway treatment before surgery. One case with a polyp-like tracheal tumor required venoarterial percutaneous cardiopulmonary support to establish adequate oxygenation before surgery. All 18 cases underwent a segmental resection of the trachea, with the average length of 3.6 rings. Postoperative recovery was uneventful for all but one patient with postintubation tracheal stenosis, who died 17 days after surgery due to a methicillin-resistant Staphylococcus aureus infection. Complications in the other patients included four cases of laryngeal nerve palsy, three of aspiration, and one patient with Horner syndrome, with a total morbidity of 27.7%. CONCLUSIONS: A tracheal resection is currently a safe procedure; however, cooperation with sophisticated airway interventional treatment teams, cardiopulmonary bypass support, or a well-trained anesthesiologist is essential for obtaining a successful outcome, especially for the cases with pre-existing severe airway obstruction.

Is T2 non-small cell lung cancer located in left lower lobe appropriate to upstage?

In the TNM classification, patients with T2 non-small cell lung cancer (NSCLC) have heterogeneous factors. The efficacy of surgery for T2 disease remains unsatisfactory. We retrospectively reviewed 268 T2 patients with non-small cell lung cancer for whom a curative approach had been attempted between January 1994 through December 2003. All patients were subjected to lobectomy, including dissection of hilar and mediastinal lymph nodes contained in pathologically proven adenocarcinoma or squamous cell carcinoma. The overall survival rates at 5 and 7 years were 58.4% and 48.5%, respectively. Five-year survival of patients with a tumor in the left lower lobe (LLL) was 38.8%; other lobe, 61.6%. Primary tumor distribution in the LLL was significantly associated with a poor survival in T2 NSCLC. In univariate analysis, tumors size less than 4 cm, tumor in the left lower lobe, histological differentiation, lymph node involvement were significantly associated with prognosis. Multivariate analysis showed that tumor in the left lower lobe (P=0.0159), histological differentiation (P=0.0071), and lymph node involvement (P=0.0266) were found to be independent prognostic factors in cases of T2 disease. In cases where the primary tumor without well differentiation is in the LLL, surgery for T2 NSCLC should be considered carefully.

Successful removal of bovine pericardium by bronchoscope after lung volume reduction surgery.

We report on a patient in whom, 10 months after lung volume reduction surgery, bovine material visibly migrated to the bronchial lumen. In this particular case, bronchoscopic treatment was successful. The patient remained well 12 months after such treatment. The report also suggests that the alternative use of absorbable material will reduce later postoperative complications.

Evaluation of the treatment of non-small cell lung cancer with brain metastasis and the role of risk score as a survival predictor.

OBJECTIVE: The modality of treatment for patients with brain metastasis from non-small cell lung cancer (NSCLC) has not yet been established. Among these patients, few survive longer than 3 years. However, a small group of these patients demonstrate a better prognosis. The objective of this study is to clarify the efficacy of treatment and evaluate factors affecting long-term patient survival. METHODS: We retrospectively reviewed the medical charts of 70 patients found to have brain metastasis from NSCLC in Fukuoka University Hospital between 1994 and 2002. These patients were grouped according to therapy received for the brain and lung and separated into two groups, as follows: LBR, lung and brain resection; LR, lung resection without brain resection. We also evaluated these groups for a set of several factors. Risk score was calculated with reference to the data from multivariate analysis, which can estimate survival. RESULTS: The number of patients who underwent lung surgery plus brain surgery was 41. In this LBR, the 1- and 3-year survival rates after treatment of brain were 66.4 and 22.9%, respectively. We found that a therapeutic strategy including surgery for primary lung and brain can afford patients an extended survival time compared to the survivals of other LR group. The 3-year survival of patients with high carcinoembryonic antigen (CEA) was 0 vs. 39.6% among patients normal for CEA. Some factors, including histological type, nodal metastasis, serum LDH and CEA, were associated with survival. The multivariate Cox model identified both adenocarcinoma histological subtype, node status and high serum CEA as independent prognostic factors, whereas serum LDH was not found to be significant. Risk score was determined in our study to estimate prognosis according to the multivariate data. From this equation, previously we can expect 1- or 3-year survival of each patient with brain metastasis from NSCLC, refer to the risk score. CONCLUSIONS: Stringent selection, i.e. low-risk score (adenocarcinoma, node-negative and normal level of CEA) of candidates for surgical treatment for primary lung and brain metastasis from NSCLC may be an acceptable and valuable approach.

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC.

OBJECTIVES: Non-small cell lung cancer (NSCLC) tissue produces numerous growth factors, which are multifunctional and considered predictive of patient survival. This study sought to evaluate the relationship between concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) in NSCLC tissue and clinicopathological factors, and determine whether these factors correlate with long-term survival. METHODS: We retrospectively investigated 71 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, for whom the primary curative approach was surgery, and who received no chemotherapy or radiotherapy prior to surgery. bFGF, VEGF, HGF were measured in extracts prepared from these 71 frozen tissue samples by ELISA. Five- and 10-year survival was obtained to determine the most important predictors of long-term survival. RESULTS: Among clinicopathological parameters, the mean concentration of bFGF was significantly higher in tissue extracts from cases involving metastatic nodal involvement (87.5+/-69.3 ng/100 mg protein) than in those without nodal involvement (57.6+/-42.5 ng; P<0.05). Levels of VEGF in adenocarcinoma (26.8+/-34.0 ng) were higher than for squamous cell carcinoma (12.2+/-13.8 ng; P<0.05). HGF levels also demonstrated histological differences (14.7+/-7.7 vs. 10.6+/-9.7 ng, P<0.05). bFGF protein levels were basically the same, but showed no statistically significant differences with respect to histological type (72.5+/-55.2 vs. 63.6+/-51.5 ng). Patients with high levels of bFGF or VEGF showed significantly worse survival rates than patients with low levels (P=0.0059; P=0.0134). In particular, high concentrations of both bFGF and VEGF correlated with markedly poor prognosis (P<0.0001). Multivariate analysis indicated that lymph node involvement and levels of bFGF and VEGF were independent prognostic factors in cases of NSCLC (adenocarcinoma or squamous cell carcinoma) involving patients who had undergone curative resection. CONCLUSIONS: Adenocarcinoma associated with lung cancer is regarded to have biological characteristics that distinguish it from squamous cell carcinoma. Node invasion may be associated with bFGF. bFGF and VEGF augment each other and are associated with leading to poor prognosis. The results of this study suggests that effective therapy to block angiogenesis may need to address at least both of these factors in cases of NSCLC.

Surgical treatment for elderly breast cancer patients over the age of 70.

Because elderly breast cancer patients differ in various biological characteristics from younger patients, it is important to clarify the clinical characteristics and treatment results of elderly patients with this disease. A total of 332 breast cancer cases (327 patients) who received surgery were divided into three groups, consisting of a premenopause group younger than 50 years of age (group A, N = 144), a postmenopause group younger than 70 years of age (group B, N = 140), and elderly cases 70 years of age or older (group C, N = 48). A positive node involvement was seen in about 40% of all cases, but the lymph node positivity of group C was significantly lower than that of group A or B. The postoperative 5-year survival rates of groups A, B, and C were 88.9%, 87.5%, and 89.4% at all stages, and 90.2%, 86.2%, and 91.4% at stages I and II, respectively. Only in group C did survival rates show no significant difference between node status. We conclude that both radical and cosmetic surgical treatments performed in elderly breast cancer patients aged 70 years or older are as effective as in younger breast cancer patients.