Evaluation of the intramammary distribution of breast lesions detected by MRI but not conventional second-look B-mode ultrasound using an MRI/ultrasound fusion technique.

The objective of this study was to evaluate the intramammary distribution of MRI-detected mass and focus lesions that were difficult to identify with conventional B-mode ultrasound (US) alone. Consecutive patients with lesions detected with MRI but not second-look conventional B-mode US were enrolled between May 2015 and June 2023. Following an additional supine MRI examination, we performed third-look US using real-time virtual sonography (RVS), an MRI/US image fusion technique. We divided the distribution of MRI-detected mammary gland lesions as follows: center of the mammary gland versus other (superficial fascia, deep fascia, and atrophic mammary gland). We were able to detect 27 (84%) of 32 MRI-detected lesions using third-look US with RVS. Of these 27 lesions, 5 (19%) were in the center of the mammary gland and 22 (81%) were located in other areas. We were able to biopsy all 27 lesions; 8 (30%) were malignant and 19 (70%) were benign. Histopathologically, three malignant lesions were invasive ductal carcinoma (IDC; luminal A), one was IDC (luminal B), and four were ductal carcinoma in situ (low-grade). Malignant lesions were found in all areas. During this study period, 132 MRI-detected lesions were identified and 43 (33%) were located in the center of the mammary gland and 87 (64%) were in other areas. Also, we were able to detect 105 of 137 MRI-detected lesions by second-look conventional-B mode US and 38 (36%) were located in the center of the mammary gland and 67 (64%) were in other areas. In this study, 81% of the lesions identified using third-look US with RVS and 64% lesions detected by second-look conventional-B mode US were located outside the center of the mammary gland. We consider that adequate attention should be paid to the whole mammary gland when we perform third-look US using MRI/US fusion technique.

Clinicopathological Features of Methotrexate-associated Lymphoproliferative Disorders in the Gastrointestinal Tract.

Methotrexate may cause methotrexate-associated lymphoproliferative disorder (MTX-LPD); however, this disease is uncommon in the gastrointestinal tract. We examined six patients with MTX-LPD in the gastrointestinal tract at our hospital. All of the lesions were ulcerative. Four cases regressed spontaneously, all of which were positive for Epstein-Barr virus-encoded small RNA by in situ hybridization. Two patients who did not regress were negative for Epstein-Barr virus RNA, one of whom received chemotherapy, and one underwent surgery. The prognosis of this disease is considered to be good. MTX-LPD should considered when ulcerative lesions are observed during endoscopy in patients receiving MTX.

Simple Fluorescence Labeling Method Enables Detection of Intracellular Distribution and Expression Level of Retinoid X Receptors.

There is no straightforward method to visualize the intracellular distribution of nuclear receptors, such as retinoid X receptors (RXRs), which are trafficked between the cytosol and nucleus. Here, in order to develop a simple fluorescence labeling method for RXRs, we designed and synthesized compound 4, consisting of an RXR-selective antagonist, CBTF-EE (2), linked via an ether bond to the fluorophore nitrobenzoxadiazole (NBD). Compound 4 is nonfluorescent, but the ether bond (-O-NBD) reacts with biothiols such as cysteine and homocysteine to generate a thioether (-S-NBD), followed by intramolecular Smiles rearrangement with an amino group such as that of lysine to form a fluorescent secondary amine (-NH-NBD) adjacent to the binding site. Fluorescence microscopy of intact or RXR-overexpressing MCF-7 cells after incubation with 4 enabled us to visualize RXR expression as well as nuclear transfer of RXR induced by the agonist bexarotene (1).

Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma.

BACKGROUND AND AIMS: Clinicians sometimes encounter papillary thyroid microcarcinoma (PMC) that is less than 10 mm, associated with lymph node metastasis. In this study, we assessed PMC clinicopathologically to clarify risk factors for poor prognosis. PATIENTS AND METHODS: Fifty-one patients who underwent thyroid surgery at Aichi Medical University from September 2009 to October 2016 were included. Patients were divided into two groups, pEX-positive (23 patients) and pEX-negative (28 patients), based on the pathological finding of thyroid capsule invasion. The former indicates that the tumor infiltrated the thyroid capsule and spread to the neighboring tissue, and the latter indicates no capsule invasion. We analyzed factors such as patient characteristics, pathological findings, and serum levels of thyroid hormones in the two groups. RESULTS: No statistical differences were observed between the two groups in gender distribution or age at surgery. Preoperative cancer diagnoses were established for more patients in the pEX-positive group than in the pEX-negative group (n = 21 and 14, respectively; P = 0.004). The mean (±SD) pathological tumor diameter was 5.42 ± 2.77 in the pEX-negative group and 8.32 ± 1.61 in the pEX-positive group (P < 0.001). No significant differences in preoperative serum levels of free T3, free T4, thyroid-stimulating hormone, or thyroglobulin were observed between the two groups. The odds ratio for node positivity in tumors invading thyroid capsules (pEX-positive) compared to those with no capsule invasion (pEX-negative) was 13.20 (95% confidence interval, 3.45-50.42). Immunohistological staining for phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and Akt (protein kinase B) revealed the facilitation of PTEN and suppression of Akt, which might indicate downregulation of the phosphoinositide 3-kinase-Akt (PI3K-Akt) cascade. DISCUSSION: In general, the prognosis of PMC is favorable. However, the prognosis is less favorable in patients with nodal metastasis or extrathyroidal invasion. It is controversial whether resection is required for proven PMCs. For PMCs associated with extrathyroidal invasion, regional lymph node resection with lobectomy should be performed due to the high risk for lymphatic spread. There might be a possibility that the natural progression of PMC seems to be controlled by the facilitation of PTEN. However, a tumor in the lateral peripheral region of the thyroid parenchyma might be associated with capsule invasion followed by lymphatic spread.

Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.

AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease. PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient. RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment. CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.

Development of Erythema Nodosum After Olaparib Treatment in a Patient With Recurrent Breast Cancer and BRCA2 Mutation: A Case Report.

BRCA1 and 2 mutations are known to be associated with breast cancer, and olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, has been shown to be effective in cells carrying these mutations in some studies. Erythema nodosum (EN), which is one adverse event of olaparib and is discussed in this paper, is considered to be a very rare condition. A 69-year-old female patient underwent left breast conservative surgery with axillary lymph node dissection for left invasive ductal breast cancer (stage IIB). Her family history included a sister who developed ovarian cancer at age 63. Five years postoperatively, systemic metastases were discovered in the lung, bone, hilar, and poststernal lymph nodes. The surgically removed metastatic lung nodule was diagnosed as an estrogen receptor (ER)-positive, progesterone receptor (PgR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative metastatic adenocarcinoma of breast cancer origin. And germline mutations of BRCA1/2 were assessed using BRACAnalysis CDx® (Myriad Genetics, Salt Lake City, UT, USA), and BRCA2 1241 delC was identified as a deleterious mutation. Oral administration of olaparib was started. On day 4 of this treatment, numerous erythematous plaques characterized by intense tenderness and infiltration appeared on the extensor surfaces of the bilateral lower legs. On the basis of the clinical findings, the lesions were diagnosed as EN. Oral prednisolone was started at the same time as olaparib discontinuation, and the EN lesions disappeared in one week. EN is an inflammatory lesion characterized by tender subcutaneous induration with a flushed surface, predominantly on the bilateral lower legs. EN occurring after olaparib administration is considered to be very rare. This article describes such a case and reviews the relevant literature.

Invasive lobular carcinoma of the breast detected with real-time virtual sonography: a case report.

BACKGROUND: Invasive lobular carcinoma (ILC) sometimes presents with unique clinical, pathologic, and radiographic features. In this case report, we describe a patient with ILC, whose initial presentation consisted with symptoms secondary to bone-marrow dissemination. In addition, the breast primary was revealed only by magnetic resonance imaging (MRI) followed by real-time virtual sonography (RVS). CASE PRESENTATION: A 51-year-old woman presented to our outpatient clinic with dyspnea on exertion. She had severe anemia (hemoglobin, 5.3 g/dL) and thrombocytopenia (platelet count, 31 × 103/mL). Bone-marrow biopsy was performed to evaluate hematopoietic function. The pathologic diagnosis was bone-marrow carcinomatosis due to metastatic breast cancer. Initial mammography followed by ultrasonography (US) failed to detect the primary tumor. On MRI, a non-mass-enhancement lesion was observed. While second-look US also did not detect the lesion, it was clearly visualized with RVS. We were finally able to biopsy the breast lesion. The pathologic diagnosis was ILC positive for both estrogen receptor and progesterone receptor, with 1 + immunohistochemical staining for human epidermal growth factor receptor 2. This case of ILC was characterized by bone-marrow metastasis. Due to decreased cell adhesion, the risk of bone-marrow metastasis is higher in ILC than in invasive ductal carcinoma, the most prevalent type of breast cancer. Biopsy of the primary lesion, which was initially only detected with MRI, was successfully performed with clear visualization during RVS, which is based on the fusion of MRI and US images. CONCLUSION: In this case report and literature review, we describe the unique clinical characteristics of ILC and a strategy for identifying primary lesions that are initially only visualized with MRI.

Ligand Screening System for the RXRα Heterodimer Using the Fluorescence RXR Agonist CU-6PMN.

Retinoid X receptor (RXR), a nuclear receptor (NR) that regulates transcription of target genes in a ligand binding-dependent manner, is of interest as a drug target. RXR agonists have been developed as therapeutic agents for cutaneous invasive T-cell lymphoma (e.g., bexarotene (1)) and investigated as potential anti-inflammatory agents. Screening systems for the binding of RXR alone have been reported. However, although RXRs function as RXR heterodimers, information on systems to evaluate the differential binding of RXR agonists as RXR heterodimers has not been available until recently. Here we show that the fluorescent RXR agonist CU-6PMN (3), designed by our group, can be useful for assessing RXR binding to PPARγ/RXRα, and that the binding data differ from those of RXRα alone. This screening method opens a new avenue for binding assays for RXR heterodimers.

Two cases of esophageal basaloid squamous cell carcinoma which achieved long-term survival by endoscopic submucosal dissection and additional chemoradiotherapy.

Herein, we report two rare basaloid squamous cell carcinoma (BSCC) cases. Esophagogastroduodenoscopy revealed a submucosal tumor-like lesion and a biopsied specimen showed a finding suspected of BSCC in both cases. Both lesions underwent endoscopic submucosal dissection with en bloc resection, and long-term survival was achieved using additional chemoradiotherapy. The standard treatment for BSCC has not been determined, and there are few reports of esophageal BSCC treated using endoscopic resection. Endoscopic submucosal dissection and additional chemoradiotherapy for superficial BSCC may be effective treatment options.

Effect of eribulin on epithelial-mesenchymal transition plasticity in metastatic breast cancer: An exploratory, prospective study.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer metastasis and treatment resistance, which worsens prognosis. In phase III trials, eribulin improved overall survival in metastatic breast cancer (MBC) patients. In preclinical studies, eribulin suppressed EMT. However, clinical data on the use of eribulin for MBC patients are limited. In this exploratory, prospective study, we examined the effect of eribulin on EMT in MBC patients. Twenty-two patients aged 44-82 years with recurrent breast cancer or MBC were treated with eribulin. Breast cancer tissue samples were obtained before treatment and on Day 15 ± 5 of the first cycle of eribulin treatment. EMT markers (E-cadherin, claudin-3, vimentin, and N-cadherin) were analyzed using western blotting. EMT changes were evaluated based on the ratio of epithelial to mesenchymal markers before and after treatment in individual tumors. E-cadherin/vimentin, claudin-3/vimentin, E-cadherin/N-cadherin, and claudin-3/N-cadherin ratios were significantly higher after treatment (p = .007, p = .005, p = .006, and p = .011, respectively). Based on E-cadherin/vimentin, 65.0% of tumors shifted to an epithelial phenotype, as compared to 66.7% based on claudin-3/vimentin, 84.6% based on E-cadherin/N-cadherin, and 71.4% based on claudin-3/N-cadherin ratios. Thus, our results showed that eribulin suppressed EMT in breast cancer tissues.

Clinical performance of digital breast tomosynthesis-guided vacuum-assisted biopsy: a single-institution experience in Japan.

BACKGROUND: The purpose of this study was to evaluate the clinical performance of Digital Breast Tomosynthesis guided vacuum-assisted biopsy (DBT-VAB) for microcalcifications in the breast. METHODS: Retrospective review of 131 mammography-guided VABs at our institution were performed. All of the targets were calcification lesion suspicious for cancer. 45 consecutive stereotactic vacuum-assisted biopsies (ST-VABs) and 86 consecutive DBT-VABs were compared. Written informed consent was obtained. Tissue sampling methods and materials were the same with both systems. Student's t-test was used to compare procedure time and the Fisher's exact test was used to compare success rate, complications, and histopathologic findings for the 2 methods. RESULTS: The tissue sampling success rate was 95.6% for ST-VAB (43/45) and 97.7% (84/86) for DBT-VAB. Time for positioning (10.6 ± 6.4 vs. 6.7 ± 5.3 min), time for biopsy (33.4 ± 13.1 vs. 22.5 ± 13.1 min), and overall procedure time (66.6 ± 16.6 min vs. 54.5 ± 13.0 min) were substantially shorter with DBT-VAB (P < 0.0001). There were no differences in the distribution of pathological findings between the 2 groups. CONCLUSION: Depth information and stable visibility of the target provided by DBT images led to quick decisions about target coordinates and improved the clinical performance of microcalcification biopsies.

Pheochromocytoma Multisystem Crisis Complicated by Severe Acute Pancreatitis.

A 43-year-old man developed headache, dizziness, abdominal pain, and vomiting. His blood pressure was 203/121 mmHg, heart rate 122 beats/min, body temperature 39.1°C, and respiratory rate 24/min. He had elevated levels of creatinine at 2.95 mg/dL and lipase at 1,364 U/L as well as an extremely low calcium level at 5.2 mg/dL. Hypertriglyceridemia and hyperglycemia were seen. Chest and abdominal computed tomography showed interstitial pneumonia, severe pancreatitis, and a right adrenal tumor. The patient also developed vertebral artery dissection and medullary infarction. After right adrenalectomy, the patient was diagnosed with pheochromocytoma multisystem crisis (PMC). Acute pancreatitis might augment numerous life-threatening manifestations of PMC.

Case report: surgical management of symptomatic pretracheal thyroid gland in a patient with dual ectopic thyroid.

BACKGROUND: Dual ectopic thyroid, a very rare condition, is defined as the simultaneous presence of ectopic thyroid tissue in two abnormal locations. Here, we report the surgical management of a patient with dual ectopic thyroid. CASE PRESENTATION: The patient was a 12-year-old boy with right para-midline swelling for 2 months. On physical examination of the upper anterior neck, there was a 4 cm × 3 cm mass that was soft, mobile, smooth, and painless. Blood examination showed euthyroidism. Neck ultrasonography showed a well-circumscribed multilocular cyst. We followed up by observation only because the patient had no local symptoms or malignancy. After 2 years, the mass gradually enlarged, so we performed surgery to improve cosmetic outcomes. Preoperative neck CT revealed both a high-density solid mass at the base of the tongue and a central low-density region surrounded by a high-density area at the pretracheal region below the hyoid. The infrahyoid mass was surgically removed, and the sublingual mass was left intact. Pathological findings showed the growth of multiple-size follicles, leading to a diagnosis of adenomatous goiter. Postoperative 123-I scintigraphy showed radioactive iodine uptake in the sublingual lesion, but none in the normal thyroid bed despite the extirpation of thyroid tissue. Postoperative thyroid hormone replacement was started for subclinical hypothyroidism. One year postoperatively, the patient became euthyroid. CONCLUSION: Surgical excision was used to manage a symptomatic cervical infrahyoid mass related to dual ectopic thyroid. Postoperatively, thyroid hormone replacement was required both to prevent enlargement of the remaining sublingual thyroid and to maintain adequate thyroid hormone levels.

Longly-attached cap can contribute to en bloc underwater endoscopic mucosal resection of 20-30 mm colorectal intramucosal lesions.

Background and study aims Underwater endoscopic mucosal resection (UEMR) is effective for colorectal intramucosal lesions. The aim of this study was to evaluate whether a longly-attached cap in UEMR improves the en bloc resection rate for 20-30 mm lesions. Patients and methods We performed a retrospective study at a tertiary institute. Candidates for the study were systematically retrieved from an endoscopic and pathological database from October 2016 to December 2020. We assessed the procedural outcomes with UEMR for lesions ≥ 20 mm in size and the clinical factors contributing to en bloc resection. Results A total of 52 colorectal lesions that underwent UEMR were included. The median procedure time was 271 (66-1264) seconds. The en bloc resection rate and R0 resection rate were 75 % and 73 %, respectively. Intraprocedural perforation occurred in one (1.9 %) case, but no bleeding occurred. Delayed bleeding occurred in one (1.9%) case, but no delayed perforation occurred. Regarding tumor size, macroscopic type, tumor location, and the presence or absence of a history of abdominal operation, there was no significant difference between the en bloc resection and piecemeal resection groups. The visibility of the whole lesion, a longly-attached cap, and sessile serrated lesions were more frequently observed in the en bloc resection group than in the piecemeal resection group ( P  < 0.001, P  = 0.01, and P  = 0.04, respectively). Multivariate analysis showed that a longly-attached cap was the only independent factor associated with en bloc resection ( P  = 0.02). Conclusions A longly-attached cap might contribute to en bloc resection.

Association between antispasmodics and detection of lesions by screening esophagogastroduodenoscopy.

Background and Aim: Whether administration of antispasmodics as a component of premedication contributes to detection of lesions by screening esophagogastroduodenoscopy (EGDS) remains unclear. Our primary aim was to investigate this possibility. Methods: The cohort in this retrospective study comprised consecutive asymptomatic individuals who had undergone screening EGDS as part of a health check-up at the Japanese Red Cross Wakayama Medical Center from October 2015 to September 2020. The investigated lesions comprised esophageal squamous cell carcinoma or adenocarcinoma, gastric adenoma or adenocarcinoma, and duodenal adenoma or adenocarcinoma. Results: Targeted lesions were detected in 72 of 31 484 participants (0.23%), 18 260 and 13 224 of whom had received and not received pre-procedure antispasmodics, respectively. The rates of detection of lesions in these groups were 0.21% (38/18260) and 0.26% (34/13224), respectively (P = 0.40). Multivariate logistic regression analysis showed no association between administration of antispasmodics and rates of detection of targeted lesions [P = 0.24, Odds ratio (95% CI): 1.46 (0.78-2.75)]. Conclusions: Antispasmodics, which were administered to more than half of the study cohort, did not improve the rate of detection of targeted lesions.

Primary Hepatic Neuroendocrine Carcinoma with Thrombocytopenia Due to Diffuse Bone Marrow and Splenic Infiltration: An Autopsy Case.

An 82-year-old man with fever and back pain was referred to our hospital and was thus found to be thrombocytopenic. A bone marrow biopsy revealed the diffuse infiltration of poorly differentiated neuroendocrine carcinoma (NEC). Computed tomography revealed a large hepatic mass. Considering the risk of bleeding due to thrombocytopenia, a needle biopsy was not performed. The patient rapidly deteriorated and died 10 days after presentation. An autopsy confirmed the diagnosis of primary hepatic NEC, with diffuse metastasis to the spleen, bone marrow, and systemic lymph nodes. This is an extremely rare case of NEC presenting with thrombocytopenia due to extensive bone marrow and splenic infiltration.

Evaluation of an MRI/US fusion technique for the detection of non-mass enhancement of breast lesions detected by MRI yet occult on conventional B-mode second-look US.

PURPOSE: The aim of this study was to verify the utility of second-look ultrasound (US) using real-time virtual sonography (RVS), a magnetic resonance imaging (MRI)/US fusion technique, in identifying MRI-detected breast lesions with non-mass enhancement (NME). METHODS: Consecutive patients who had one or more NME lesions detected by MRI yet occult on the subsequent second-look US in conventional B (cB)-mode imaging were enrolled in the study between June 2015 and April 2020. Supine MRI of the lesions was performed and, using its data, second-look US using RVS was performed. RESULTS: Twenty patients with 21 NME lesions were included. The overall median lesion size on prone MRI was 23 mm (range, 5-63 mm). Supine MRI identified all the 21 NME lesions, and second-look US using RVS successfully detected 18 (86%) of them. RVS-guided biopsy was performed for histopathological evaluation, showing that nine of the 18 lesions were benign and the other nine malignant. Of the nine malignant lesions, two (22%) were invasive cancer and seven (78%) were ductal carcinoma in situ. In four of five patients who underwent prone MRI for preoperative evaluation, the diagnosis was benign and surgery was conducted as originally planned. In the other patient, the diagnosis was malignant and contralateral breast-conserving surgery was added. Three (14%) of the 21 NME lesions had no RVS correlates and were judged to be benign after 24-month follow-up. CONCLUSION: The results suggest that second-look US using RVS helps identify MRI-detected NME lesions that are occult on cB-mode second-look US.

Airway obstruction requiring tracheal intubation after fine-needle aspiration of the thyroid gland: a case report.

BACKGROUND: There have been no reports of tracheal intubation for airway obstruction after acute thyroid swelling following fine-needle aspiration (FNA) of the thyroid gland. CASE PRESENTATION: A 58-year-old woman with a 22 mm × 13 mm right hypervascular thyroid nodule underwent FNA once with a 22G needle under ultrasonographic guidance. Shortly after the aspiration, ultrasound revealed hypoechoic swelling with a crack-like pattern. The patient was observed under bed rest in the Fowler position and received intravenous steroids. A computed tomography (CT) scan showed swelling not only of the thyroid but also of the retropharyngeal space, and the patient complained of difficulty swallowing saliva. Laryngeal fiberscopy revealed protrusion of the posterior pharyngeal wall, edematous changes in the mucosa of the pharynx and epiglottis, and retention of saliva. The patient was intubated awake and hydrocortisone was administered every 8 h. She was extubated 3 days after FNA and discharged without any complications. CONCLUSIONS: When neck swelling is noticed after FNA, ultrasonographic findings are especially important to assess potential causes. If airway obstruction is suspected, CT findings and fiberscope observation of the pharynx provide particularly useful information.