[A Case of Breast Cancer Brain Metastases Successfully Treated with Pembrolizumab Therapy after Disease Progression with Atezolizumab Therapy].

A 39-year-old woman was diagnosed with right breast cancer(cT3N1M0, cStage ⅢA, triple negative type). After preoperative chemotherapy using dose-dense doxorubicin and cyclophosphamide, followed by dose-dense paclitaxel every 2 weeks, the patient underwent right modified radical mastectomy. Postmastectomy radiotherapy to the right chest wall and right supraclavicular area and oral capecitabine therapy were administered. Computed tomography 1 year after surgery showed multiple lung metastases. The patient received atezolizumab and nab-paclitaxel therapy. Six months after the first chemotherapy, metastatic brain tumor in right frontal lobe, 12 mm in size, was observed along with enlargement of lung metastases. Because the brain tumor showed rapid growth after CyberKnife therapy, emergency tumorectomy was performed. One month after cranial surgery, new 3 brain metastases were appeared. Gamma knife therapy to brain metastases and pembrolizumab, carboplatin, gemcitabine therapy was started. Although insufficient doses of carboplatin and gemcitabine were administered due to bone marrow suppression, no progression was observed for about 1 year after initiation of pembrolizumab therapy. Pembrolizumab therapy may show anti-tumor effect to breast cancer brain metastases, even after a failure of atezolizumab therapy.

[A Case of Breast Cancer Complicated by Fibrous Dysplasia That Was Difficult to Differentiate from Bone Metastasis].

A 58-year-old woman with HER2-negative hormone-sensitive postmenopausal breast cancer underwent preoperative bone scintigraphy and CT to search for distant metastasis. Bone metastasis was suspected in the spinous process of the seventh cervical vertebra. MRI revealed a mass that was hypointense on T1- and T2-weighted images and hyperintense on diffusion- weighted images, with intense contrast enhancement, indicating bone metastasis at cT1N0M1, Stage Ⅳ(M: OSS). The patient underwent partial mastectomy and sentinel lymph node biopsy. The postoperative diagnosis was pT2N0cM1, Stage Ⅳ, with the status of bone metastasis being key to staging. PET-CT showed uptake in the spinous process of the seventh cervical vertebra but no other metastatic findings. However, solitary bone metastasis to the cervical spinous process is atypical. CT-guided needle biopsy confirmed benign fibrous dysplasia, and the final diagnosis was breast cancer at pT2N0M0, Stage ⅡA. Fibrous dysplasia is characterized by impaired osteogenesis leading to fibroplasia and commonly occurs in the skull, jaw bones, ribs, and limbs. Solitary fibrous dysplasia in the cervical spinous process is rare. The lesion was asymptomatic and pathologically benign, requiring no treatment. The patient underwent postoperative radiation therapy for the conserved breast and is followed up with endocrine therapy.

[A Case of Intraductal Papilloma of the Male Breast].

Male breast cancer accounts for approximately 1% of the overall incidence of breast cancer. We report a rare case of intraductal papilloma(intracystic papilloma)in a 73-year-old man, which was suspected to be breast cancer as it presented as an approximately 6 cm mass below the left nipple in various imaging studies. The patient was aware of a mass measuring a few millimeters below the left nipple for 5 years, but had not sought treatment. He visited our department 3 months after redness and pain were noted around the nipple; the mass had enlarged. Palpation revealed a 6 cm smooth-surfaced mass as well as nipple retraction; diagnostic imaging showed a cystic tumor with a solid internal structure. Fine-needle aspiration cytology and core needle biopsy did not indicate a definitive diagnosis, and a left mastectomy and sentinel lymph node biopsy were performed based on a preoperative diagnosis of breast cancer. Pathological examination confirmed the diagnosis of intraductal papilloma, based on findings such as infarction-induced hemorrhagic necrosis, stromal and epithelial proliferation, apocrine metaplasia, and squamous epithelial metaplasia. Reports of a large-diameter intraductal papilloma(intracystic papilloma)suspicious for breast cancer in men are rare; therefore, surgical resection and detailed histopathological exploration of the whole tumor were required.

[A Case of Primary Acinic Cell Carcinoma of the Breast].

Acinic cell carcinoma(ACC)is an invasive malignancy primarily characterized by proliferation of tumor cells that resemble acinar cells of the salivary glands and pancreas. ACC of the mammary glands is rare. We report a case of primary ACC of the breast. Two masses were revealed in the left mammary gland of a 57-year-old woman who visited our hospital through screening mammography. The lesions were identified as synchronous multiple breast carcinoma of 2 different histological types; ACC and tubulolobular carcinoma. For treatment, left mastectomy and sentinel lymph node biopsy were performed, followed by postoperative chemotherapy and endocrine therapy. Hematoxylin-eosin staining of ACC revealed abundant acinar- like structures formed by tumor cells with prominent eosinophilic granules in the cytoplasm. Immunostaining was positive for S-100 protein, α1-antichymotrypsin, α1-antitrypsin, and lysozyme. The tumor cells were negative for estrogen, progesterone, and HER2 receptors, which indicated that they had a triple-negative phenotype. Although primary ACC of the breast is regarded as low-grade triple-negative breast carcinoma with a favorable prognosis, further accumulation of cases may be needed to elucidate the biological features of ACC and investigate appropriate therapeutic strategies.

[Importance of Local Therapy for Oligometastatic Breast Cancer-A Case Report].

A case of successful local treatment for metachronous oligometastases to the lung and mediastinal lymph nodes in a postmenopausal woman with breast cancer is presented. A 44-year-old woman underwent partial mastectomy and left axillary lymph node dissection for right breast cancer. Thirteen years and 3 months after the operation, she was referred to our hospital for a right lung mass detected by mass screening and diagnosed with a metastatic lung tumor from left breast cancer following CT-guided biopsy. She was simultaneously diagnosed with right breast cancer, and pulmonary metastasectomy, right partial mastectomy, and sentinel lymph node biopsy were performed. Two years after the second operation, follow-up CT showed a swollen lymph node at the pre-tracheal space, and endobronchial ultrasound-guided transbronchial needle aspiration confirmed the diagnosis of metastatic breast cancer. The mediastinal lymph node metastasis showed no change in size for 2 years and 7 months with fulvestrant therapy, and no other metastases were found. Proton beam therapy of 60 GyE in 30 fractions was administered to the metastatic lymph node. Substantial tumor shrinkage with no severe toxicity was observed, and to date, the patient has remained disease-free. More cases need to be studied to investigate the appropriate strategy for local therapy in patients with oligometastatic breast cancer.

CA19-9-producing lung metastasis after surgery for papillary thyroid carcinoma: report of a case.

Measuring tumor marker levels following cancer treatment can be useful. Although serum thyroglobulin is a useful marker after total thyroidectomy for papillary thyroid carcinoma (PTC), it is not a reliable marker for patients with a high titer of anti-thyroglobulin antibodies or when transformation to undifferentiated carcinoma has occurred. The female patient in this case report underwent total thyroidectomy and oral I-131 therapy for PTC at the age of 47 years, followed by cervical lymph node and lung resections for metastases, 3 and 11 years later, respectively. She also received oral I-131 therapy and external beam radiotherapy for mediastinal lymph node metastases. The lymphadenopathy lesions progressed and multiple lung metastases were detected when she was 61 years of age. She died at the age of 62 years. The serum CA19-9 level had gradually increased in association with enlargement of the recurrent lesions and immunostaining of CA19-9 in the pulmonary metastasis was intense. Thus, we consider that measuring the level of serum CA19-9 is an effective tool for evaluating disease status after surgery for PTC.

A computational model of the hippocampus that represents environmental structure and goal location, and guides movement.

Hippocampal place cells (PCs) are believed to represent environmental structure. However, it is unclear how and which brain regions represent goals and guide movements. Recently, another type of cells that fire around a goal was found in rat hippocampus (we designate these cells as goal place cells, GPCs). This suggests that the hippocampus is also involved in goal representation. Assuming that the activities of GPCs depend on the distance to a goal, we propose an adaptive navigation model. By monitoring the population activity of GPCs, the model navigates to shorten the distance to the goal. To achieve the distance-dependent activities of GPCs, plastic connections are assumed between PCs and GPCs, which are modified depending on two reward-triggered activities: activity propagation through PC-PC network representing the topological environmental structure, and the activity of GPCs with different durations. The former activity propagation is regarded as a computational interpretation of "reverse replay" phenomenon found in rat hippocampus. Simulation results confirm that after reaching a goal only once, the model can navigate to the goal along almost the shortest path from arbitrary places in the environment. This indicates that the hippocampus might play a primary role in the representation of not only the environmental structure but also the goal, in addition to guiding the movement. This navigation strategy using the population activity of GPCs is equivalent to the taxis strategy, the simplest and most basic for biological systems. Our model is unique because this simple strategy allows the model to follow the shortest path in the topological map of the environment.

Combination treatment with antibiotics and surgical lung resection for Mycobacterium abscessus pulmonary infection in a breast cancer patient.

A 51-year-old woman was admitted to our hospital because of pneumonia after chemotherapy with doxorubicin and cyclophosphamide for left breast cancer. The patient was diagnosed with Mycobacterium abscessus pulmonary infection by the detection of M. abscessus complex (MABC) in sputum cultures. However, MABC is intrinsically resistant to most of the antibacterial agents, and MABC pulmonary disease outcomes with modern antibiotic treatment are currently the worst among all mycobacterial species. We herein report the successful treatment of M. abscessus pulmonary infection by a combination treatment with antibiotics and surgical lung resection.

A cell model in the ventral visual pathway for the detection of circles of curvature constituting figures.

The contour of an arbitrary figure can be represented as a group of circles of curvature in contact with it, with each curvature circle represented by its center OC and radius r. We propose a series of cell models for detecting this circle, which is composed of a lateral geniculate nucleus (LGN) cell, nondirectionally selective (NDS) simple cell, and curvature-circle detection cell (CDC). The LGN and NDS simple cells were previously modeled. The CDC has been modeled as follows. Each tangent in contact with this circle is detected by an NDS simple cell that performs the Hough transformation of LGN cell responses, and then this tangent is transformed to a three-dimensional (3D) normal line in a CDC column. This transformation has been named a 3D normal-line transform. Performing this transformation for all tangents causes a CDC at the intersection of these normal lines to fire most intensively, and thus the OC and r of the circle is detected as the coordinates of this intersection. Therefore, the CDC has been modeled as this 3D normal-line transform. Based on this CDC, we model two types of constancy CDC: a position-invariant CDC and a curvature-invariant CDC. These three types of CDC reflect the response to various stimuli in actual area V4 cells. In order to validate these CDC types neurophysiologically, we propose an experimental method using microelectrodes. Cell models previously reported correspond to this hierarchy: the S1, S2, and C2 cells correspond to the NDS simple cell, CDC, and position-invariant CDC, respectively.

Durable clinical benefit of letrozole in leptomeningeal metastasis of breast cancer.

A case of a woman in her 60s with breast cancer, whose leptomeningeal metastasis (LM) of breast cancer improved remarkably with letrozole monotherapy, is reported. The patient complained of numbness of her left hand and hoarseness, followed by progressive asymmetric extremity weakness and a bladder and rectal disturbance. The patient had undergone surgery for left breast cancer 18 years earlier and was concerned about recurrence of breast cancer, but there were no typical findings with some imaging modalities. The third lumbar puncture showed the malignant cytology of breast cancer, and the patient was diagnosed with recurrent breast cancer. Her performance status was very poor, and it was difficult to administer systemic chemotherapy. Letrozole was started because immunohistochemistry was positive for estrogen and progesterone receptors. After 4 months of letrozole therapy, the symptoms improved gradually. LM has a poor prognosis, and there is little evidence on which to base treatment, but hormone therapy may be an option for LM when the tumor is hormone receptor-positive, slow growing, and has a small volume.

Specific spatio-temporal activities in the cerebral ganglion of Incilaria fruhstorferi in response to superior and inferior tentacle nerve stimulation.

In terrestrial gastropod mollusks (slugs and snails), olfaction is the dominant sensory modality guiding various kinds of behavior. Anatomical studies indicate that olfactory information is processed in the brain (the cerebral ganglion) in two lobes in particular: the procerebrum (PC) and the metacerebrum (MtC). This implies that olfactory functions emerge from simultaneous and cooperative processing in the PC and the MtC. However, no previous physiological study has investigated the activity in these two lobes simultaneously. In the present study, the activity evoked by electrical stimulation of the olfactory nerves, the superior and inferior tentacle nerves, was recorded optically from the whole cerebral ganglion of the terrestrial slug, Incilaria fruhstorferi. The results indicated that the evoked activity in the PC and the MtC showed two specific spatio-temporal patterns. First, when either set of nerves was stimulated, the activity of the medial neuropilar region of the MtC (the mMtC) always preceded the activity in the PC. Second, stimulation of the superior tentacle nerves activated the medial and lateral halves of the mMtC almost evenly, whereas stimulation of the inferior tentacle nerves activated the lateral half of the mMtC more strongly than the medial half. These results suggest that the activated region of the mMtC plays an important role in olfactory processing, especially with respect to the functional differences between the superior and inferior tentacles.

Liver resection for HER2-enriched breast cancer metastasis: case report and review of the literature.

Liver metastasis from breast cancer usually results in the development of systemic metastasis. We report a breast cancer patient with an early isolated liver recurrence who survived more than 7 years with no recurrence. She was treated with aggressive HER2-directed chemotherapy and hepatic metastasectomy. Local hepatectomy with effective medical oncological therapy with curative intent is worth trying in patients with breast cancer liver metastasis.

Pictorial cues constrain depth in da Vinci stereopsis.

"da Vinci stereopsis" is defined as depth seen in a monocular object occluded by a binocular one, and the visual system must solve its depth ambiguity [Nakayama, K., & Shimojo, S. (1990). da Vinci stereopsis: Depth and subjective occluding contours from unpaired image points. Vision Research, 30, 1811-1825]. Although fused images include various pictorial features, effects of pictorial depth cues have never been systematically investigated in da Vinci stereopsis. To examine this, we created stereograms consisting of a monocular bar flanked by binocular bars with a fixed large horizontal separation, in which the monocular bar induced a subjective occluding edge. Manipulating vertical size or contrast of the bars could affect the depth of the monocular bar. Conflicting these cues revealed that the effect of vertical size was stronger than that of contrast in all our subjects. Measurements of the depth indicated that the relative vertical size of the bars quantitatively determined the perceived depth, of which levels had large inter-subject differences. All these experiments indicate that the visual system can use the pictorial depth cues as a constraint to determine the depth of monocular elements.

[A model of bipedal walking adaptable to an unpredictably dynamic environment].

Modern science has been developed through concept of subject-object separation. That is, nature has been cordoned off from human beings and objectified. We have attempted to discover ideal world laws wherein we can consider nature as homogeneous. The real world, however, is by far more complicated than what natural sciences have so far been able to decipher. There are many problems that cannot be effectively addressed with the existing scientific technology. Because the real world is so unpredictable and dynamic, it is impossible to objectify it in advance and apply traditional methodology. This real world problem arises especially in information processing systems, that is, the recognition and the motion control systems coping with the real world. The current information systems can only handle explicit and complete information. Life is an intrinsic part of nature. To be both pliant and sturdy in a complex environment requires autonomy capable of creating the information needed to control the self. It forms the premise for the cognizance and control of life systems that exist in reality. To "live," a life system must independently forge a harmonious relationship with an unlimited environment. It requires that the life system be capable of creating the information necessary for self-control. It is this autonomy that clearly distinguishes the world of life systems from the physical world. Here, we will show an example of adaptive bipedal walking under an indefinite environment.

Tonsillar metastasis of gastric cancer.

Metastasis from a malignant tumor to the palatine tonsils is rare, with only 100 cases reported in the English-language literature. Tonsillar metastasis from a gastric cancer is very rare. We report here a case of palatine tonsillar metastasis after gastric cancer surgery. The patient was an 88-year-old woman who had gastric cancer with abdominal wall invasion. She had undergone a distal gastrectomy with abdominal wall resection and D2 lymph node dissection. Histologically, the tumor was primarily a moderately differentiated adenocarcinoma. It was stage IV (T4, N1, M0) using TNM clinical classification. The patient developed pharyngeal discomfort and abdominal pain and was hospitalized during the follow-up period, 1 year 9 months post-operatively. Multiple lung metastases, Virchow's lymph node metastasis, and adrenal metastasis were observed. A mass of 2.5 cm was also observed in the right palatine tonsil. It was diagnosed as a moderately differentiated adenocarcinoma, a metastasis from gastric cancer. There was a concern of asphyxiation due to hemorrhage of the tumor; however, the tumor dislodged approximately 10 days after biopsy and tonsillar recurrence was not observed. The patient died 1 year 10 months post-operatively. In the literature there are cases with tonsillar metastases where surgical treatment, radiotherapy, and chemotherapy were performed and extension of survival was seen. Tonsillar metastasis is a form of systemic metastasis of a malignant tumor, and there is a high risk for asphyxiation from tumor dislodgement or hemorrhage. Thus, it is important to recognize tonsillar metastasis as an oncologic emergency.