Prognostic significance of PD-L1-positive cancer-associated fibroblasts in patients with triple-negative breast cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1. METHODS: Immunohistochemical staining (primary antibodies of 73-10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined. RESULTS: Thirty-four (55.7%) patients were positive for CAF PD-L1 (73-10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73-10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044-0.891; p = 0.035). CONCLUSIONS: CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73-10 assay may be suitable for immunostaining CAF PD-L1.

Direct comparison of magnetic resonance imaging and pathological shrinkage patterns of triple-negative breast cancer after neoadjuvant chemotherapy.

BACKGROUND: We aimed to investigate the usefulness of magnetic resonance imaging (MRI) and histopathological shrinkage patterns to formulate a predictive equation for estimating residual tumor size after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients. METHODS: We enrolled 34 TNBC patients who underwent MRI before and after NAC. The MRI and histopathological shrinkage patterns were analyzed and classified into five categories-types I and II (concentric shrinkage without or with surrounding lesions, respectively), type III (shrinkage with residual multinodular lesions), type IV (diffuse contrast enhancement in the entire quadrant), and non-visualization. The residual tumor sizes following MRI and histopathological examination were also compared. RESULTS: The most common MRI and histopathological shrinkage pattern was type I (41.2% and 38.2%, respectively), followed by non-visualization (26.5% and 32.4%, respectively); the concordance rate between MRI and histopathological shrinkage patterns was 41.2%. There was a strong correlation between MRI tumor size and pathological tumor size (r = 0.89). Based on these findings, a predictive equation for pathological tumor size was formulated as follows: pathological tumor size (mm) = 1.1502 × (MRI tumor size [mm]) + 8.4277. CONCLUSIONS: Our equation may aid accurate preoperative assessment. Further studies are needed to determine its predictive value and applicability.

[A Case of Pulmonary Tumor Thrombotic Microangiopathy(PTTM)Diagnosed During Chemotherapy for Metastatic Breast Cancer].

A 46-year-old woman with metastatic breast cancer developed dyspnea that progressed relatively rapidly during chemotherapy. Chest-abdominal CT revealed wedge-shaped infiltration shadow, and cardiac catheterization revealed elevated pulmonary artery pressure. Aspiration cytology of pulmonary arterial blood was performed and malignant cells were confirmed. Chemotherapy was difficult to continue because of deterioration in general condition, and she died 7 days after diagnosis. This time, we report a case of PTTM for which pulmonary arterial blood cytology was useful for diagnosis.

[Radiation-Induced Breast Angiosarcoma after Conservative Surgery for Breast Cancer].

We present the case of an 88-year-old woman who had undergone breast conserving surgery for left breast cancer 8 years ago.She received postoperative radiotherapy(total dose of 60 G/30 Fr)to the residual breast together with endocrine therapy.She underwent skin biopsy after having had a red skin tumor in the left breast.Angiosarcoma was diagnosed and chemotherapy and radiotherapy were initiated.The patient is alive without recurrence 8 months after chemotherapy.

[Temporary Home Management of a Refractory Pleural Effusion with an Indwelling Catheter].

BACKGROUND: Pleurocentesis and pleurodesis are the common treatments for pleural effusion. However, most home-visit physicians usually hesitate to perform these treatments for patients confined at home. CASE: A 51-year-old woman developed breast cancer(ER+, HER2-)at the age of 39 years. She underwent a partial mastectomy of the right breast. Nine years later, metastatictumors in the lungs, and hilar and mediastinal lymph nodes were found. The patient was admitted to our hospital because of the progression of pleural effusion and dyspnea. On the day of admission, the aspiration catheter was placed in the left lung with continuous suction, but pleurodesis could not be performed as the left lung did not re-expand enough. As the patient requested to go home as soon as possible, she was discharged with the catheter in place. Three days after the discharge, the home-visit physician drained 340 mL of fluid through the catheter. Six days after the discharge, the patient was readmitted to the hospital with malaise and dyspnea, but no signs of complications associated with the indwelling catheter use were observed. The patient died 4 days after the readmission. CONCLUSION: This case suggests that draining fluid using an indwelling pleural catheter as a home-based healthcare measure is one of the simplest and safest options.

[A Case of Ductal Carcinoma In Situ(DCIS)Diagnosed by Excisional Biopsy with Benign Cytology Findings of Fine-Needle Aspiration].

Nipple discharge is a common symptom and frequently results from benign tumors. However, there is a 5-30% risk of malignancy. A 65-year-old woman presented at the hospital because of bloody nipple discharge in her right breast. She had noticed an abnormal nipple discharge for several months. Mammography showed focal asymmetric densities without calcification in the middle outer quadrant of her right breast. Ultrasonography indicated a 1.5×1.1 cm sized cyst with fluid-fluid level. Breast MRI showed a simple cyst with a benign contrast enhancement pattern. No malignant cells were observed by fine-needle aspiration. Considering the low sensitivity of mammography and breast MRI to DCIS, we performed an excisional biopsy. Histological examination revealed that the lesion was DCIS. The patient underwent right total mastectomy and was diagnosed with low grade DCIS(ER-positive, PgR-positive, HER2-negative). She continues endocrine therapy with an aromatase inhibitor.

[Abnormal Nipple Discharge].

BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of the milk duct or lobule. Ductography and fiberoptic ductoscopy have beenadvocated as the mainprocedures inpatien ts with nipple discharge. METHODS: We investigated the usefulness of microdochectomy(MD)by using indocyanine green(ICG)fluorescence imaging. ICG and indigo carmine were injected into the mammary duct. A periareolar incision was made, and a fluorescence image of the demarcated mammary duct segment was obtained. CONCLUSION: MD using indocyanine green fluorescence imaging is a useful procedure in guiding subsequent breast surgery in the treatment of nipple discharge.

HtrA1 Is Specifically Up-Regulated in Active Keloid Lesions and Stimulates Keloid Development.

Keloids occur after failure of the wound healing process; inflammation persists, and various treatments are ineffective. Keloid pathogenesis is still unclear. We have previously analysed the gene expression profiles in keloid tissue and found that HtrA1 was markedly up-regulated in the keloid lesions. HtrA1 is a serine protease suggested to play a role in the pathogenesis of various diseases, including age-related macular degeneration and osteoarthritis, by modulating extracellular matrix or cell surface proteins. We analysed HtrA1 localization and its role in keloid pathogenesis. Thirty keloid patients and twelve unrelated patients were enrolled for in situ hybridization, immunohistochemical, western blot, and cell proliferation analyses. Fibroblast-like cells expressed more HtrA1 in active keloid lesions than in surrounding lesions. The proportion of HtrA1-positive cells in keloids was significantly higher than that in normal skin, and HtrA1 protein was up-regulated relative to normal skin. Silencing HtrA1 gene expression significantly suppressed cell proliferation. HtrA1 was highly expressed in keloid tissues, and the suppression of the HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development by accelerating cell proliferation and remodelling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

[Evaluation of the Small Excision Using a Sonographically Visible Breast Biopsy Marker(HydroMARK®)].

In case an operation is necessary after an ST-VAB for microcalcification, a wide excision needs to be performed because of the loss of marking. The HydroMARK®breast biopsy marker can be visualized using an ultrasound or mammography and facilitates a small excision. Six months after the deployment, all markers were visualized using an ultrasound. Thus, Hydro MARK®can decrease the sample size(11 g)in open biopsies and correctly diagnose ADH. However, no HydroMARK®cases were diagnosed with ADH in large samples(44 g, 32 g). Five malignant histology cases underwent mastectomy, and the distance between the HydroMARK®and tumor was 300 mm. HydroMARK®appears to be a safe and effective marker after a stereotactic biopsy for calcification, which facilitates an exact small excision of lesion surgically.

[Radiotherapy and Eribulin Mesylate for Mediastinal Node Metastasis from Breast Cancer-A Case Report].

A69 -year-old woman was diagnosed as having local advanced breast cancer. She was treated with neoadjuvant chemotherapy( AC followed by paclitaxel)and followed up with left total mastectomy with axillary lymphadenectomy for breast cancer(pT3N1aM0, Stage ⅢA, ER positive, PgR positive, and HER2 negative). She received adjuvant therapy with chest wall irradiation and an aromatase inhibitor. Two years after the mastectomy, mediastinal lymph node and rib metastases and dissemination appeared. We changed the regimen to capecitabine. She continued the capecitabine therapy for 7 years and was found to have multiple lung metastasis. Therefore, we chose eribulin mesylate therapy. Ten days after eribulin mesylate (1.0mg/body)was first administered, she suddenly had difficulty breathing, and chest CT revealed left low lobe atelectasis. The superior mediastinal lymph node had grown rapidly and compressed the left main bronchus and superior vena cava. To reduce the lymph node size, we started radiotherapy(50 Gy/25 Fr)for the superior mediastinal area in addition to the eribulin mesylate therapy. After the radiotherapy, chest CT revealed a remarkable reduction of lymph node size and full pulmonary reexpansion. One year after the radiotherapy, she is continuing treatment without systemic progression.

[A Successful Treatment of Locally Advanced Breast Cancer with Using Mohs' Paste and Chemotherapy - A Case Report].

Foul smell and large amounts ofexudate, bleeding are the most common and serious symptoms with locally advanced breast cancer(LABC). Mohs' paste is made ofa mixture ofzinc chloride and used for treatment ofmalignant skin tumors. Recently some reports show that Mohs' paste is useful for treatment of malignant tumor including unresectable breast cancer and skin metastasis ofcancer. Mohs' paste is useful for reducing symptoms such as foul smell and exudate, Bleeding. We report a successful case of treatment for LABC with using Mohs' paste and chemotherapy and surgery.

[Local Control by Mastectomy in Advanced Breast Cancer with Liver Metastasis after Chemotherapy, Radiotherapy, and Hyperthermia - A Case Report].

Advanced breast cancer has a poor prognosis compared to early breast cancer; however, quality of life and radical operation can be improved in some case by using multidisciplinary treatment. A 54-year-old woman was examined at the hospital because of an enlarging tumor in the left breast. She was aware of a lump for 3 years. Results of the initial examination indicated invasive ductal carcinoma with liver metastasis. She first received chemotherapy(AC followed by weekly paclitaxel). After 4 courses of weekly paclitaxel, computed tomography revealed axillary lymph nodes involved in the axillary vein. Operation was difficult and conversion therapy was administered. The patient underwent radiotherapy, hyperthermia, and hormone therapy. After 1 year from the start of hormone therapy, the metastasis had disappeared and the patient underwent operation in our unit. Eight months after operation, no recurrence was observed.

[A Case of Shock Due to nabPTX Administration Successfully Treated with Cytokine Adsorption Therapy].

The patient was a 71-year-old woman with ER(+), PgR(-), HER2(3+), and Ki-674 2% breast cancer. After surgery for left breast cancer(Bt+Ax), epirubicin, cyclophosphamide therapy was administered as postoperative adjuvant chemotherapy, and nabPTX plus trastuzumab therapy was started sequentially. The patient was hospitalized due to severe neutrope- nia(neutrophils 0/mm3)from nabPTX, but her condition stabilized after admission. However, the patient suddenly went into shock after 3 days and was thus transferred to the ICU. Her general condition was rapidly improved through cytokine adsorption therapy in the ICU. After 5 days, she was extubated and wheeled back to a general ward. She was discharged without problems in the succeeding months. In this case, FN or cardiovascular diseases was ruled out, and engraftment syndrome was considered given that cytokine adsorption therapy significantly improved the patient's condition. Considering the risk for severe neutropenia in nabPTX administration, clinicians should exercise caution when administering the drug.

[Examination of Stereotactic Mammotome Biopsy for Microcalcification in Our Hospital].

We introduced stereotactic mammotome biopsy(ST-MMT)for the purpose of screening and other institutions. There are many benign cases to be diagnosed by pathological findings, so it is thought to be necessary to examine the adaptation of STMMT again. We examined the performance of ST-MMT in a case of a non-palpating calcification lesion. Between August 2013 and December 2016, ST-MMT biopsies were performed for 247 microcalcified lesions revealed by mammography(in both breasts in 9 patients; twice in the ipsilateral breast in 2 patients). The mean age of all patients was 46 years(range, 24- 89 years). We found 39 cases(15.8%)of breast cancer. A final diagnosis of breast cancer was made in 39 patients, who comprised 0% of those with Category 2, 53.8% of those with Category 3, 35.9% of those with Category 4, and 10.3% of those with Category 5. Regarding the morphology and distribution of microcalcifications, breast cancer accounted for 46.2%, 5.1%, 2.6%, 35.9%, 7.7%, and 2.6% of the cases with small round/clustered, amorphous/clustered, pleomorphic/clus- tered, pleomorphic/linear segmental, and fine linear/clustered patterns, respectively. Also, we examined each of the patients, (1) who underwent mammography for medical examinations, (2) who underwent mammography performed at other institutions, (3) who underwent follow-up for microcalcifications and postoperative follow-up mammography. The proportions of breast cancer diagnoses were (1) 11.4%, (2) 20.6%, and (3) 7.1%. Proportions of Category 3 breast cancer were (1) 10.3%, (2) 38.5%, and (3) 5.1%. Among the cases in which ST-MMT was performed in this study, Category 3 accounted for more than half. However, 10.9%(21/192 lesions)were diagnosed as malignant in Category 3. The diagnosis of breast cancer in pa- tients who underwent mammography performed at other institutions was not observed in 79.4%(104/131 lesions), and among the 104 lesions, as a result of reassessment of calcification in our hospital, Category 2 was also included. Calcification in Category 2 lesions was benign in all cases. It was suggested that the indication for ST-MMT biopsy could be further narrowed down by being careful not to over-diagnose.

[Strut Adjusted Volume Implant(SAVI) - An Interim Report of Patient Satisfaction and Outcomes].

BACKGROUND: Strut adjusted volume implant(SAVI)was approved by the Food and Drug Administration(FDA)for the treatment of breast cancer in 2006. MATERIAL AND METHODS: The phase II study was conducted to investigate the activity and safety of SAVI in breast cancer patients. Criteria for SAVI treatments were N0, T<2 cm, and age≥40. After patients underwent breast-conserving surgery, they received SAVI twice a day×5 days(34 Gy). The primary endpoint are feasibility and safety. Second endpoint are local recurrence rate and cosmesis. RESULTS: Three patients were enrolled and the median duration of administration is 18.7 days(17-20). Further, the most common treatment-related adverse events were thickening and redness of skin(grade 1/2), while there was no deformity of breast in each case. CONCLUSION: The current study demonstrated that SAVI is well tolerated treatment in breast cancer patients and may be convenient for use in patient treatment.

[Serous Carcinoma of the Peritoneum with Metastases to the Breast and Axillary Lymph Nodes].

Metastasis of peritoneal serous carcinoma to the breast and axillary lymph nodes is rare. We present a case of serous carcinoma of the peritoneum with metastases to the breast and axillary lymph nodes. A 72-year-old woman was diagnosed with Stage III peritoneal serous carcinoma in November 2009; she was treated with 6 courses of paclitaxel and carboplatin. In December 2015, she had a palpable mass(2×2 cm)and enlarged axillary lymph nodes. Mammography did not reveal any mass(C1)and ultrasonographic examination demonstrated a partially ill-defined hypoechoic mass with a diameter of 8.7× 7.1 mm. Cytological examination of the axillary lymph node revealed malignancy; breast carcinoma metastasis was suspected and the patient underwent breast-conserving surgery. Histopathological examination of the specimens(breast and axillary lymph nodes)revealed adenocarcinoma, and immunohistochemistry analysis showed that the specimens were CK7(+), CK20(-), CA125(+), PAX8(+), and GCDFP15(-). Taken together, the results indicated peritoneal serous carcinoma metastases to the breast and axillary lymph nodes. CONCLUSION: We report a case of serous carcinoma of the peritoneum with metastases to the breast and axillary lymph nodes.

[Effectiveness of Postoperative Physical Therapy for Upper-Limb Impairments after Breast Cancer Treatment].

Previous studies have reported the benefits of beginning rehabilitation immediately after breast cancer surgery for improving motor function. However, most studies have not evaluated the long-term struggles patients face after hospital discharge in resuming their previous activities and socialparticipation. Furthermore, the intervention methods and effects of rehabilitation for such activities have not been evaluated. We investigated the effectiveness of postoperative physical therapy for upperlimb impairments after breast cancer treatment. Fifty-four women in the postoperative period of surgery for breast cancer participated in the study. Range of motion in the ipsilateral shoulder was initially limited after surgery and recovered during the study period: shoulder flexion range of motion reached a mean value from 110 to 155 degrees, mean abduction was from 70 to 110 degrees, and mean externalshoul der rotation was from 69 to 85 degrees. Lymphedema was present in 5 women. In conclusion, physical functional disabilities were present in the late postoperative period for breast cancer survivors, and limited range of motion in their shoulders negatively affected their functional capacity and quality of life. Therefore, we need to increase rehabilitation care after breast cancer surgery immediately.

Good response to chemotherapy spares irradiation for extrarenal rhabdoid tumor conferring better activities of daily living.

A 7-year-old girl with stage IIA extrarenal rhabdoid tumor near the left cubital fossa received preoperative chemotherapy and surgical resection with median nerve reconstruction followed by postoperative high-dose chemotherapy. As preoperative chemotherapy resulted in decreased tumor size, disappearance of fluorodeoxyglucose-uptake, and pathologic complete response with total tumor resection, irradiation was successfully spared to avoid injury to the reconstructed nerve and inhibition of normal bone development. Two years after diagnosis, recurrence has not been observed and median nerve palsy is improving. This case suggests that radiation therapy could be spared for clinically and pathologically chemotherapy-good-responders in case total surgical resection is achieved.

Treatment for infection of artificial dura mater using free fascia lata.

Synthetic artificial dura mater materials, such as expanded polytetrafluoroethylene sheets, are widely used in dura mater reconstruction in cases involving brain tumors or trauma surgery. In patients with postoperative infection related to the use of artificial dura mater, surgical debridement of the infected wound and removal of the artificial dura mater materials are necessary to control infection. In cases involving cerebrospinal fluid leakage, dura mater reconstruction must be performed immediately. Many useful techniques for performing dura mater reconstruction to treat postoperative infection have been reported; however, some have drawbacks with respect to the need for microvascular anastomosis or difficulties in obtaining watertight closure. We successfully treated 6 patients with postoperative artificial dura mater infection using free thigh fascia lata. Some surgeons believe that the use of free fascia in infected wounds is dangerous because free fascia is a non-vascularized tissue. However, performing complete debridement and covering such free fascia with well-vascularized tissue allow the fascia to become vascularized and tolerant of infection. Therefore, if the blood flow in the scalp is acceptable after a sufficient debridement, free fascia lata can be used for reconstruction in patients with postoperative infection of artificial dura mater. Furthermore, skull reconstruction can be performed safely and easily with solid-type artificial bone, sometimes combined with tissue expansion, thus resulting in good aesthetic outcomes.

Multipotent stem cells are effectively collected from adult human cheek skin.

Skin-derived precursor (SKP) cells are a valuable resource for tissue engineering and regenerative medicine, because they represent multipotent stem cells that differentiate into neural and mesodermal progenies. Previous studies suggest that the stem cell pool decreases with age. Here, we show that human multipotent SKP cells can be efficiently collected from adult cheek/chin skin, even in aged individuals of 70-78years. SKP cells were isolated from 38 skin samples by serum-free sphere culture and examined for the ability to differentiate into neural and mesodermal lineages. The number of spheres obtained from adult facial skin was significantly higher than that of trunk or extremity skin. SKP cells derived from cheek/chin skin exhibited a high ability to differentiate into neural and mesodermal cells relative to those derived from eyelid, trunk, or extremity skin. Furthermore, cheek/chin skin SKP cells were shown to express markers for undifferentiated stem cells, including a high expression level of the Sox9 gene. These results indicate that cheek/chin skin is useful for the recovery of multipotent stem cells for tissue engineering and regenerative therapy.