Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice.

Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.

[Elderly Advanced Breast Cancer Effectively Treated with Locoregional Therapy-A Case Report].

We report a case of advanced breast cancer in an elderly patient effectively treated with locoregional therapy. The patient was an 81-year-old woman who presented with an increasing right breast lump. The tumor was 55 mm in diameter, accompanied by fixation to pectoral muscle. A core needle biopsy for right breast tumor led to a diagnosis of mucinous carcinoma, positive for estrogen receptor(ER)and progesterone receptor(PgR), negative for HER2/neu. The Ki-67 positive cell index was 10%. A bone scintigraphy revealed multiple bone metastases, so, we confirmed the diagnosis as T4cN2aM1, Stage Ⅳ. She initiated endocrine therapy by letrozole. By changing the endocrine therapy to toremifene followed by fulvestrant, the therapy achieved a partial response. However, the size of the primary tumor increased accompanied by bleeding, and surgical resection of the right breast was performed for local control. The locoregional surgery was effective, improving the patient's quality of life. She was administered lapatinib as anti-HER2 therapy in addition to the endocrine therapy. Two years and 6 months after surgery, there has been no worsening of bone metastasis or appearance of visceral metastasis.

[Recurrent Breast Cancer with Bone Metastasis Effectively Treated with Abemaciclib plus Endocrine Therapy-A Case Report].

We report a case of recurrent breast cancer with bone metastasis in a premenopausal woman. A 46-year-old woman underwent mastectomy for right breast cancer 6 years ago. Histopathological diagnosis was invasive ductal carcinoma, T2N3aM0, stage ⅢC. She received adjuvant chemotherapy and irradiation followed by tamoxifen. Four and a half years after surgery, serum tumor marker levels elevated, and bone metastasis in the sacral region was revealed by PET-CT scan. After suppressing ovarian function with LH-RH agonist, we switched the endocrine therapy from tamoxifen to letrozole with a CDK4/6 inhibitor. Five months after starting administration of abemaciclib, the bone metastasis disappeared on PET-CT. The elevated tumor markers normalized and have continued to decrease. Abemaciclib combined with endocrine therapy was significantly effective as first-line treatment for premenopausal women with metastatic breast cancer.

Oral benzo[a]pyrene administration attenuates dextran sulfate sodium-induced colitis in mice.

Benzo[a]pyrene (BaP) is an environmental pollutant produced by combustion processes and is present in grilled foods as well as in tobacco smoke. BaP acts as an agonist for the aryl hydrocarbon receptor (AHR), and is metabolized by AHR-inducing enzymes. BaP metabolism can result in either detoxification or metabolic activation, the latter leads to an increased risk of disease, particularly lung cancer and cardiovascular disease, in a context-dependent manner. Although AHR activation has been thought to protect against inflammatory bowel disease, it remains unknown whether BaP exerts a protective or deleterious effect on colitis. In this study, we examined the effect of oral BaP administration on colitis induced by dextran sulfate sodium (DSS) in mice, an animal model of inflammatory bowel disease. BaP administration attenuated weight loss, shortening of the colon, disease activity index scores, and histological damage in DSS-induced colitis mice. BaP also suppressed colonic expression of inflammation-associated genes and plasma interleukin-6 secretion induced by DSS treatment. BaP-DNA adduct formation, a marker of BaP metabolic activation, was not enhanced in the colon after DSS treatment. Thus, oral BaP exerts an anti-inflammatory effect on DSS-induced colitis, without the toxicity associated with metabolic activation. The results provide insights into the disease-specific roles of BaP.

[Relationships Gastric Stasis in the Remnant Stomach and Interdigestive Migrating Motor Complex in Patients after Pylorus-Preserving Gastrectomy for Early Gastric Cancer].

The demerit of pylorus-preserving gastrectomy(PPG)is the postprandial abdominal fullness(PAF)with gastric stasis in the remnant stomach(GSRS). We investigated the relationship between clinical findings and GSRS, and between GSRS and interdigestive migrating motor complex(IMMC)in PPG patients. A total of 30 patients(17 men and 13 women, mean age of 62.3 years)after PPG for early gastric cancer(Billroth Ⅰ)were divided into 2 groups(group A; 18 patients with GSRS, group B; 12 patients without GSRS). The relationship between GSRS including clinical findings and IMMC was studied from 1.5 to 3 years after operation. A catheter equipped with a micro-tip force transducer was inserted transnassally into the remnant stomach and duodenum in a supine position, and the IMMC was studied. All patients were Stage ⅠA(mucosal cancer, no lymph node metastasis, no distant metastasis). The remnant stomach was 1/3 compared with stomach size before operation. The length of the antral cuff in group A(1.5±0.2 cm)was significantly shorter than group B(3.2±0.3 cm)(p =0.0004). Appetite was significantly recognized in group B compared with group A(p=0.0067). PAF was significantly recognized in group A compared with group B(p=0.0001). Reflux esophagitis was found in group A more than group B. Early dumping syndroms did not found significant differences in both groups. In endoscopic esophagogastric finding of the remnant stomch, gastritis with GSRS was significantly found in group A compared with group B(p=0.0001). The IMMC was significantly recognized in group B compared with group A(p<0.0001). The occurrence of the PAF due to the GSRS may be caused by abscens of the IMMC.

[Role of Pudendal Sensory Nerve in Patients with or without Fecal Incontinence after Low Anterior Resection for Lower Rectal Cancer].

To clarify the pudendal sensory nerve(PSN)play in preventing fecal incontinence(FI)after low anterior resection(LAR) for lower rectal cancer, the PSN function was studied at 6 months after LAR. A total of 36 patients aged 42.0 to 79.0 years (23 males and 13 females with a mean age of 62.0 years)who underwent LAR for laparoscopic radical cystectomy(LRC) were enrolled in the present study. Based on postoperative F1, these patients were divided into 2 groups[group A; patients with FI(n=12), group B; patients without FI(continence, n=24)]. These were compared with group C(n=32, control subjects, 18 males and 14 females aged 40.0 to 76.0 years with a mean age of 61.8 years). Anal mucosal electric sensitivity (AMES)threshold was measured [at the upper 1 cm oral side from dentate line(DL); a, DL; b, and lower zones 1 cm anal side from DL; c]. FI after LAR was also evaluated by the Wexner score(WS). All patients were pathological Stage Ⅰ(25 patients: T1, N0, M0; 11 patients: T2, N0, M0). Group A had a significantly larger proportion of males than group B(p< 0.05). The distance of anastomosis from anal verge(DAAV)in group A(2.4±1.8 cm)was significantly shorter than in group B(4.4±0.9 cm)(p<0.001). WS from 6 to 10 comprised 25.0% of group A, 11 to 15 comprised 50.0%, and 16 to 20 comprised 25.0%. All patients in group A(WS; 8 or more)were incontinent. In contrast, all patients in group B(WS; 0) and C(WS; 0)were continent. Patients in pre-operative defecation(WS; 0)were also continent. On the AMES(a, b, c), sensitivity of patients in group A(6.4±1.1, 5.1±0.5, 4.9±0.6 mA)was significantly higher than in groups B(2.6±0.5, 2.4 ±0.4, 2.5±0.6 mA)and C(2.3±0.4, 2.1±0.4, 2.3±0.5 mA)at all zones(p<0.001). FI after LAR with a short DAAV, especially male, may be PSN dysfunction due to operative damage of PSN.

[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].

We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.

[Phyllodes Tumor of the Breast Occurring near Postoperative Fibroadenoma Scar-A Case Report].

We report the case of a phyllodes tumor of the breast occurring near a postoperative scar of fibroadenoma of the breast. The patient was a 41-year-old female who had a lump in the left breast, and underwent surgical resection of the tumor 5 years ago at another hospital.The pathological diagnosis of the tumor was fibroadenoma, and surgical margin was negative. The patient underwent ultrasonography every year at the treatment hospital.Five years later, the patient noticed a tumor in her left breast and visited our hospital.The tumor was 30mm in diameter and situated near the postoperative scar.A core needle biopsy for breast tumor led to the diagnosis of a phyllodes tumor.Surgical resection was performed with 5mm margins, and pathological analysis of the surgical specimen revealed a benign phyllodes tumor.The surgical margins were not involved.One year and 6 months after surgery, no metastases or recurrence were reported.

[Breast Papilloma with Rapid Growth Difficult to Distinguish from Carcinoma-A Case Report].

We report a case of papilloma of the breast with rapid growth in a 39-year-old female who had a lump in the left breast. The follow-up for the breast tumor was performed at another hospital.Three years after her first visit, 3 tumors measuring 1.8 cm, 0.5 cm, and 0.3 cm in diameter were detected. The patient visited our hospital to diagnose these tumors. We performed core needle biopsy for the tumor, and the pathological diagnosis was benign papilloma.After 1 year, the tumor grew to 3.0 cm in diameter, and we repeated the core needle biopsy. The pathological diagnosis remained as benign papilloma; however, the ultrasonography and MRI results showed that the tumor was malignant.Surgical resection was performed for the tumors, and pathological analysis of the surgical specimen revealed 3 benign papillomas with no involvement of the surgical margin.Six years after surgery, no recurrence was reported.

[Usefulness of Automated Breast Ultrasound for Deciding on a Surgical Approach in a Patient with Breast Cancer- A Case Report].

Since breast reconstruction has been covered by health insurance, we can choose a procedure that combines the cosmetic satisfaction of patients with curability. We report about a patient with breast cancer that who underwent nipple-sparing mastectomy after evaluating the intraductal spread by automated breast ultrasound system(ABUS), while hand held ultrasound( HHUS)showed only limited information on the intraductal spread of the lesion. A 52-year old woman with an abnormal screening finding was referred to our hospital. HHUS showed an irregular and poorly defined hypoechoic mass lesion with a lactiferous duct extending to directly under the nipple. A core needle biopsy revealed invasive ductal carcinoma. We performed ABUS to assess the intraductal spread in the lesion because the patient requested breast reconstruction. The coronal section of the breast in the ABUS did not showintraductal spread. We, therefore, decided to perform a nipple-sparing mastectomy and sentinel lymph node biopsy. Intraoperative evaluation by frozen and permanent sections showed negative margins. The ABUS findings helped in the evaluation of the intraductal spread of the lesion and in the choice of the optimal procedure for the patient.

[Usefulness of Breast Ultrasound in Follow-Up of Post-Operative Metachronous Contralateral Breast Cancer-A Case Report].

Mammography is the standard screening toolfor post-operative breast cancer, with annualcheck -ups recommended; however, it misses some cancers. We report a case a metachronous contralateral breast cancer detected by breast ultrasound 8 years and 6 months after operation. A 72-year-old women visited our hospital for follow-up 8 years and 6 months after the operation. She was diagnosed with right breast cancer at 63 years of age and underwent partial mastectomy with axially lymph node dissection. The pathological diagnose was scirrhous carcinoma. After chemotherapy and radiation therapy, she underwent screening with annual examinations. The mammography finding was normal, but an ultrasound showed a mass lesion in the contralateral breast. The pathological diagnosis of the biopsy specimen was mucinous carcinoma. A history of breast cancer is known to suggest an increased risk of metachronous contralateral breast cancer. Therefore, regular follow-up with breast ultrasound, not only mammography, is recommended.

[A Case of an Elderly Individual with Breast Cancer Diagnosed as Paget's Disease after Mastectomy].

We report here a case of a 78-year-old woman, who underwent mastectomy for breast cancer. Mammography showed a mass in the right MO area with an unclear boundary. Ultrasound examination revealed an irregular mass of 40×29×19mm in the right C region. Dynamic contrast-enhanced MRI showed a 34mm tumor with contrast effect in the C area of the right breast. We performed a core needle biopsy on the mass, and the histopathological diagnosis was apocrine carcinoma(ER-, PgR-, HER2 3+, and Ki-67 30%)of clinical T2N0M0, stageⅡA. Right mastectomy and sentinel lymph node biopsy were performed. In the postoperative pathological examination, the main lesion was apocrine carcinoma(ER-, PgR-, HER2 3+, Ki-67 20%)and Paget's disease(ER-, PgR-, HER2 3+, Ki-67 30%). After surgery, the patient was given trastuzumab therapy.

[Treatment for Breast Cancer in an Elderly Male Patient-Report of a Case].

Breast cancer in male is comparatively rare. We encountered a case of breast cancer in an elderly male who was treated with consideration of age. A 78-year-old male consulted our hospital with a lump on his right breast. The tumor was 3 cm in diameter and was palpable in the E area of his right breast, accompanied by pain. Mammography showed an indistinct mass in the S area. Ultrasonography revealed a well-defined and rough, lobulated mass. Core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. Metastatic work-up revealed no evidence of metastasis. The patient underwent mastectomy with sentinel lymph node(SN)biopsy and axial lymph node dissection(Ax)because of positive metastasis in an SN. The pathological findings from the surgically resected specimens indicated solid-tubular carcinoma. Lymph node metastases were observed in an SN(1/1)and Ax(1/3). On immunohistochemistry, tumor cells tested positive for estrogen and progesterone receptors and negative for HER2/neu protein expression. The Ki-67 labeling index was 14%. Postoperatively, the patient has not received chemotherapy, but received hormone therapy as adjuvant therapy considering his age. Nine months after the surgery, the patient is well, and metastasis has not appeared.

[Advanced-Stage Breast Cancer Discovered by Cervical Lymphadenopathy in an Elderly Patient-Report of a Case].

Breast cancer spreading beyond the regional lymph nodes from the primary lesion is considered to be difficult to cure. Although systemic therapy is common for the treatment of metastatic breast cancer, standard therapy is difficult in some cases. We encountered a case of advanced-stage breast cancer detected by cervical lymphadenopathy in an elderly patient. An 82-year-old woman consulted an otolaryngologist for left cervical lymphadenopathy. On receiving the biopsy result, she was referred for a suspected metastatic lymph node from breast cancer. The tumor was 40mm in diameter and was palpable in the CD area of her left breast, accompanied by pain. Ultrasonography showed an irregular-shaped mass. Core needle biopsy was performed, and the pathological diagnosis was invasive lobular carcinoma. Her body check-up revealed multiple enlarged lymph nodes from the left axilla to the supraclavicular and cervical areas. We diagnosed her clinical stage with T2N3cM1, stage Ⅳ(LYM). We proceeded with surgery to alleviate the symptom. Breast reduction surgery was performed for the left breast. The pathological findings from the surgically resected specimens indicated invasive lobular carcinoma. After the surgery, 5-fluorouracil(5-FU)drug was orally administered. Cervical lymphadenopathy decreased, and visceral metastasis has not appeared.

[A Case of Sentinel Lymph Node Biopsy for Breast Cancer in an Elderly Man].

A 75-year-old man noted an elastic hard tumor under his left areola.Mammography showed a microlobulated mass, so he was diagnosed with category Ⅳ breast cancer.Ultrasonography showed a circular hypo-echoic mass that was 21mm in diameter with a moderately indistinct border.Based on core needle biopsy, the tumor was diagnosed as invasive ductal carcinoma.We performed a whole-body check-up, and he was diagnosed with T1N0M0, StageⅠ breast cancer.The patient underwent mastectomy and sentinel lymph node biopsy.The pathological diagnosis based on the resected surgical specimen was invasive ductal carcinoma, positive for ER and negative for PgR and HER2/neu protein expression, and the Ki-67 positive cell index was 20%.The surgical margins were negative, and there was no metastasis in the sentinel lymph nodes.He was administered endocrine therapy as adjuvant therapy.Two years after the surgery, he remains well without metastases.

[A Case of Duplicated Cancer Simultaneously Causing Breast and Endometrial Cancer].

Recently, with the increase in the number of young cancer patients, we often encounter multiple primary cancer(MPC). In MPC, careful examination is necessary because the treatment order and policies change greatly depending on the stage and prognosis of each tumor. We report a case of synchronous MPC of endometrialcancer and breast cancer. The patient was a 40-year-old woman who underwent endometrial cytology by a previous doctor due to illicit bleeding. As a result of the diagnosis of classⅢB, she underwent gynecological examination in our hospital. Endometroid adenocarcinoma Grade 2 was diagnosed based on endoscopic findings. On pelvic MRI, a lesion adjacent to the neck showed a low signal in the uterine body compared to that in the endocardium. During the preoperative examination, CT showed contrast nodules in the right breast, and ultrasonography was performed at the department of breast surgery. Ultrasonography showed a low-echo mass of 23 mm in the right upper midline region. The needle biopsy results were papillotubular cancer(ER-negative, PgR-negative, HER2 1+, Ki-67 77%). Based on these findings, right breast cancer and endometrial cancer were diagnosed. Initially, we performed right mastectomy and sentinel lymph node biopsy; we then performed pancreatectomy in the gynecology department 2 weeks after discharge. After surgery, gynecology studied 6 courses of TC therapy, and currently, EC is undergoing breast surgery.

[The Diagnostic Problem of Automated Breast Volume Scanner(ABUS)for a Breast Cancer Patient with Dementia-A Case Report].

The patient was an 84-year-old woman.She had presented with a mass on her right breast.Mammography revealed an illdefined mass.Handheld ultrasonography(HHUS)revealed a low echoic mass, 25mm in diameter, on the AC area of her right breast.An automated breast volume scanner(ABUS)was not useful for detecting the lesion because the patient had dementia and restless body movements.A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma, which was positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.We examined her whole body and made a diagnosis of T2N0M0, StageⅡA.She underwent a muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma, positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.The surgical margins were negative for malignancy, and no metastasis was observed in the sentinel lymph node.She was given endocrine as adjuvant therapies.Three years after the surgery, she was well without metastases.Patients with dementia could not use ABUS.HHUS will be useful for these patients.

[The Diagnostic Problem of the Automated Breast Volume Scanner(ABUS) for Paget Disease-A Case Report].

The patient, a 41-year-old woman, presented with an elastic soft tumor on her left breast. Sore skin was observed on the left nipple and areola. Mammography revealed poor extension at the left nipple surrounding skin. A hand-held ultrasonography( HHUS)device and automated breast volume scanner(ABUS)did not detect the thickening of the skin. Surgical biopsy was performed. The skin lesion was diagnosed as Paget disease. We examined her whole body and made a diagnosis of Tis N0 M0, stage 0. The patient underwent a mastectomy and sentinel lymph node biopsy. The pathological diagnosis on the basis of the resected surgical specimen was invasive ductal carcinoma, negative for ER and PgR, and positive for HER2/neu protein expression, and the Ki-67-positive cell index was 30%. The surgical margins were negative, and no metastasis was found in the sentinel lymph node. She was given trastuzumab as adjuvant therapy. Two years after the surgery, she was well without recurrence.

[A Case of Synchronous Bilateral Breast Cancer in an Elderly Patient].

We encountered a case of synchronous bilateral breast cancer in an elderly patient. A 75-year-old woman visited our hospital because she was identified with an abnormality on mammography during breast cancer screening. An elastic hard tumor 2.0 cm in diameter was detected in the A area of her right breast. Mammography showed an irregular tumor shadow with spicula in the right breast and micro-calcifications in her left breast. Ultrasonography showed a low echoic lesion 20mm in size in the A area of her right breast and a low echoic area 5mm in size in her left breast. Histological examination of core needle biopsy specimens revealed invasive ductal carcinoma in both breasts. Synchronous bilateral breast cancer was diagnosed. Bilateral muscle-preserving mastectomy with sentinel lymph node biopsy was performed. Postoperative histology revealed bilateral invasive ductal carcinoma without lymph node metastasis that was positive for ER and PgR, was negative for HER2, and had a Ki-67-positive cell index of 20% in the right breast(T1N0M0, Stage Ⅰ), and that was positive for ER, was negative for PgR and HER2, and had a Ki-67-positive cell index of 5% in the left breast(T1N0M0, Stage Ⅰ). The surgical margins were negative. She was administered endocrine therapy as adjuvant therapy for 5 years after the surgery. Eight years after the surgery, she was well without metastasis.

[Study of the Therapeutic Effect and Neutrophil Lymphocyte Ratio in Breast Cancer Patients Who Received Eribulin].

BACKGROUND: The neutrophil lymphocyte ratio is reported to be a poor prognostic factor in each carcinoma, and the possibility of predicting the therapeutic effect of chemotherapy, for example, is being studied. In this study, we measured the NLR before and after administration of eribulin and the NLR before and after the final administration in breast cancer patients and examined the relationship with the therapeutic effect. METHODS: Eleven primary breast cancer patients were examined after eribulin was administered; PD was confirmed eventually, and administration was discontinued. The NLR was determined before the first administration of eribulin and 7 days after the administration; the NLR before the final administration and after the last administration were each tested with p<0.05 as the significance level and using the t test. RESULTS: The average value of NLR before initial administration was 4.07±2.11, and the average value after 7 days of administration was 2.47±1.97. The NLR before initial administration tended to be higher, and a significant difference was observed(p<0.05). The average NLR value before the final administration was 4.02±2.04, and the average value of the NLR after the final administration was 3.19 ±1.76, showing no significant difference(p=0.27, NS).