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In the United States, Europe, and Asia, a consensus has been reached that there is a higher risk of breast cancer in high density breasts. However, there are some contrary reports that suggest the absence of an association between breast composition and breast cancer subtype; thus, there is conflicting evidence. The purpose of this study was to investigate trends in the incidence of breast cancer subtypes according to breast composition and analyze the survival rates in Japanese women.Between 2007 and 2008, 1258 Japanese patients with invasive breast cancer who underwent mammography and obtained a pathological diagnosis in our institution were included in the study. We compared cancer subtypes with breast composition types (dense and non-dense breast), and classified them based on initial mammography findings. Information on 5- and 10-year survival rates was collected by chart review for patients with dense and nondense breasts. Statistical analysis was performed using the Pearson's chi-square test for breast composition and cancer subtype. The effect of breast composition on mortality was examined using a multivariate Cox proportional hazards model, and adjusted hazard ratios were calculated.No significant difference was found between breast cancer subtype and breast composition (P = .08). Five-year (log-rank test, P = .09) and 10-year (log-rank test, P = .31) survival rates were not significantly different between breast composition types.There was no significant association between breast composition and cancer subtypes. There was also no significant difference in the prognosis between patients with and without dense breasts.

The development of mRNA vaccines and oral drugs against SARS-CoV-2 has been useful in protecting against Covid-19 infection. Since then, however, many variants of delta and omicron strains with enhanced infectivity and immune escape capacity have emerged. A 7-amino acid random peptide ribosome display library screening system was used to perform a rapid in vitro screening of peptide aptamers that universally bind to the SARS-CoV-2 wild-type, delta, and Omicron variant BA.1, BA.2, and BA.5 spike RBD (Receptor Binding Domain). Screening resulted in four peptide aptamers that showed positive binding reactions in ELISA. Interestingly, Amino Acid Sequence Determination of the four clones predicted that three of the four clones contain 2 ~ 3 Cys residues in their sequences, forming a complex higher-order structure with disulfide (S-S) bonds. The 7-amino acid random peptide ribosome display library screening system allows for rapid in vitro screening of peptide aptamers that bind to other unknown emerging infectious disease pathogens that may be pandemic in the future. The peptide aptamers are as small as 30 amino acids and can be easily synthesized and purified as peptides or proteins, or simply used as mRNA drugs.

A 37-year-old African–British man was referred to our hospital for detailed examination because of persistent fever, swelling and pain in both ankle joints, and blurred vision for two months. Inguinal lymph node biopsy showed a large number of epithelioid granulomas without necrosis. Granulomatous anterior uveitis, nephropathy, high serum angiotensin-converting enzyme activity, and high serum-soluble interleukin-2 receptor were observed, and the diagnosis of systemic sarcoidosis was made. His serum creatinine was 1.4 mg/dL and hematuria, leukocyturia, and urine protein were also seen. The renal biopsy finding was mesangial proliferative glomerulonephritis, with no findings of granuloma formation or tubular interstitial nephritis. Immunofluorescence staining showed deposition of IgG, C3, and C1q in the mesangial region. IgG3 was dominant in subclass staining. There was no monoclonality on kappa and lambda staining. Electron microscopy showed predominant deposition in the mesangial region with some subepithelial and endothelial deposition. His hematuria and leukocyturia disappeared with steroid therapy, suggesting sarcoidosis-related nephropathy. A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region is presented. No cases of such histological findings have been reported so far, and it is necessary to analyze further cases to clarify the pathogenic significance of the renal biopsy findings observed in this case.

Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole‐exome sequencing identified extensive copy‐neutral loss of heterozygosity (LOH) in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma. In addition, several truncating germline heterozygous variants in tumor suppressor genes, including RBL2 and FBXW12, became homozygous as a result of LOH. Collectively, we speculate that extensive LOH in teratoma cells may force heterozygous germline variants to become homozygous, which, in turn, may contribute to the development of neuroblastoma with the acquisition of additional chromosomal changes., A model of malignant transformation from teratoma to neuroblastoma.

Tumor human epidermal growth factor receptor 2 (HER2) status is defined by either protein expression using immunohistochemistry (IHC) or gene amplification using fluorescence in situ hybridization (FISH). Approximately 20% of HER2-positive breast cancer is HER2 IHC 2+/FISH-positive. Unlike trastuzumab, it has not been studied whether the response to trastuzumab emtansine (T-DM1) differs according to HER2-positive status. We retrospectively identified and reviewed medical records of all patients with HER2-positive advanced breast cancer (ABC) who received T-DM1 in our hospital from October 2013 to December 2016. We compared the objective response rate (ORR) and progression-free survival (PFS) between patients in the HER2 IHC 3+ group and those in the HER2 IHC 2+/FISH-positive group. A total of 39 patients (IHC 3+: n = 32; IHC 2+/FISH-positive: n = 7) were analyzed. Nineteen (48.7%), 13 (33.3%), and 29 (74.4%) patients had received at least one prior chemotherapy, more than three lines of chemotherapy, and prior pertuzumab for ABC, respectively. ORR was significantly higher in the IHC 3+ group than in the IHC 2+/FISH-positive group (53.3% vs. 0%, P = 0.024). Median PFS was 7.9 months in the IHC 3+ group versus 3.9 months in the IHC 2+/FISH-positive group (hazard ratio 0.68; 95% confidence interval 0.28-1.69, P = 0.408). Among the HER2-positive ABC patients treated with T-DM1, ORR was significantly worse in HER2 IHC 2+/FISH-positive than in HER2 IHC 3+ patients. Median PFS tended to be shorter in patients with HER2 IHC 2+/FISH-positive.

OBJECTIVE. IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and fibrosis in various organs. The objective of this study is to investigate CT findings of IgG4-related lesions involving the upper urinary tract and compare them with those of urothelial carcinomas. MATERIALS AND METHODS. This study reviewed pretreatment CT images of 13 consecutive patients with IgG4-related disease with upper urinary tract lesions and 80 consecutive patients with urothelial carcinomas. The findings assessed were laterality, location, growth pattern, margins, internal structure, presence of calcification and lipid component, enhancement pattern, and extraurinary findings. RESULTS. Bilaterality (p < 0.0001), an extramural growth pattern (p < 0.0001), a greater number of affected segments (p = 0.04), and a gradual dynamic enhancement pattern (p < 0.001) were significantly more frequent in patients with IgG4-related disease. With regard to extraurinary findings, paraaortic fat stranding (p = 0.03), presacral fat stranding (p < 0.001), fat stranding of the pelvic walls (p < 0.001), and aortic involvement (p < 0.001) were seen more frequently in patients with IgG4-related disease; on the other hand, there was no statistically significant difference in terms of frequency of pancreatic involvement. Hydronephrosis and renal involvement were seen more frequently in patients with urothelial carcinoma, although the difference was not statistically significant. CONCLUSION. CT findings suggestive of IgG4-related upper urinary tract lesions in comparison with urothelial carcinoma are bilateral and have a longer urinary tract involvement and exhibit an extramural growth pattern, ill-defined margins, a gradual enhancement pattern, aortic involvement, and fat stranding in the paraaortic, presacral, or pelvic wall areas.

Few studies had been published regarding imaging findings of skin adnexal tumors. We experienced two giant cases of them with a characteristic mushroom-like growth pattern. MRI showed a circumscribed mushroom-like shaped mass extruding from the subcutaneous tissue with microcystic lesions. Although differentiation between benignancy and malignancy may be difficult by radiological examinations, MRI may be helpful to identify its origin and differentiate soft tissue tumors with skin adnexal tumors in having these imaging findings.

This study aims to develop and validate prediction models for the number of all heatstroke cases, and heatstrokes of hospital admission and death cases per city per 12 h, using multiple weather information and a population-based database for heatstroke patients in 16 Japanese cities (corresponding to around a 10,000,000 population size). In the testing dataset, mean absolute percentage error of generalized linear models with wet bulb globe temperature as the only predictor and the optimal models, respectively, are 43.0% and 14.8% for spikes in the number of all heatstroke cases, and 37.7% and 10.6% for spikes in the number of heatstrokes of hospital admission and death cases. The optimal models predict the spikes in the number of heatstrokes well by machine learning methods including non-linear multivariable predictors and/or under-sampling and bagging. Here, we develop prediction models whose predictive performances are high enough to be implemented in public health settings., In the context of climate change, heatstroke is expected to become an increasingly relevant public health concern. Here, the authors develop and validate prediction models for the number of all heatstroke cases in different cities in Japan.

Background: The peak age at diagnosis of breast cancer differs between patients in Asian countries (40 - 50 years), and those in Western countries (60 - 70 years). With the increasing use of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased significantly in younger Asian women. Nevertheless, our knowledge of the clinicopathological features and prognosis in young patients with DCIS is relatively limited. We aimed to compare the clinicopathological features of younger patients with that of older patients with DCIS and to evaluate their prognostic factors.Methods: A total of 1445 women were diagnosed with DCIS between the years 2005 and 2015. Patients with the past history of breast cancer and managed without surgery were excluded. The young age group included patients Citation Format: Seki A, Matsuda N, Kajiura Y, Kobayashi D, Hayashi N, Tsunoda H, Suzuki K, Yoshida A, Takei J, Yamauchi H. Clinicopathological characteristics and prognosis of young patients with ductal carcinoma in situ [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-05.

Background: Lymphocyte predominant breast cancer subgroup, defined as ≥ 50% stromal tumor-infiltrating lymphocytes (sTILs), is associated with high pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome. In a cohort of triple negative (TNBC) and HER2+ breast cancer (BC) patients treated with NAT, we aimed to assess the predictive and prognostic value of pre- and post-NAT sTILs and the information provided by the change in sTILs during NAT. Materials and methods: Two-hundred and nine consecutive patients (n=80 TNBC; and n=129 HER2+) who received NAT between 2001 and 2009 in our institution were evaluated. Pre-NAT sTILs were assessed on biopsy sample (baseline) and post-NAT sTILs on surgical specimens just for non-pCR patients. sTILs level was categorized as low 0-9%, intermediate 10-49%, and high ≥50%. The change in sTILs during NAT was calculated as the absolute difference between pre- and post-NAT sTILs. We evaluated the association of pre-NAT sTILs and pCR, and the association between pre- and post-NAT sTILs, and their change with relapse-free survival (RFS). Results: Overall pCR rate was 37.8% (31.3% for TNBC, 41.2% for ER+/HER2+BC, 42.3% for ER-/HER2+BC). In each subtype, pre-NAT low sTILs group was significantly associated with lower pCR rate. During the median follow-up period of 98 months, 44 recurrences (21.1%) were observed. For TNBC, low pre-NAT sTILs group was associated with higher recurrence risk compared with int/high sTILs (HR=4.675 [2.013-10.859], p Conclusion: In TN and HER2+ BCs, tumors with low pre-NAT sTILs have a low likelihood to achieve a pCR (predictive marker). In TNBC, low pre-NAT sTILs were associated with higher recurrence risk. In non-pCR TNBC patients, both low pre- and post-NAT sTILs were associated with shorter RFS. These results suggest that sTILs information should be taken into account when additional post-surgery treatments are considered in non-pCR patients. Citation Format: Ochi T, Giampaolo B, Murai M, Nozaki F, Kobayashi D, Iwamoto T, Niikura N, Suzuki K, Yamauchi H, Hayashi N. Predictive and prognostic value of stromal tumor-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-31.

Background Nipple-sparing mastectomy (NSM) is an alternative procedure to skin-sparing mastectomy (SSM) for selected patients who undergo immediate reconstruction. However, the evidence of long-term oncologic safety of NSM has not been established. In this study, we aimed to compare the prognosis of breast cancer patients who underwent NSM to those who underwent SSM with immediate reconstruction. Methods The clinicopathological factors including recurrence site, pathologic stage, nipple-tumor distance, histological type, lymphovascular invasion, margin status, ER, PgR and HER2 status of stage 0–III primary breast cancer patients who underwent NSM or SSM with immediate primary reconstruction with tissue expander from our breast center database was retrospectively assessed. Patients with a nipple tumor distance of Results The median follow-up period was 71 months (range: 10 - 131 months) for the NSM group and 79 months (range: 9 - 140 months) for the SSM group. There were no significant difference of clinicopathological factors between the NSM group and the SSM group, except of the larger diameter of tumor in the SSM group. NSM was performed for 60 patients (32%) with stage 0, 71 patients (37%) with stage I, and 59 patients (31%) with stage II/III. SSM was performed for 185 patients (26%) with stage 0, 268 patients (37%) with stage I, and 276 patients (37%) with stage II/III. Local recurrence was found in 11 (5.8%) patients in the NSM group and in 44 (6.0%) patients in the SSM group. In the NSM group, only one (0.5%) patient had local recurrence in the nipple areola complex. In terms of DFS and overall survival (OS) rate, there was no difference between the NSM group and the SSM group (DFS; 89.5% vs 89.2%, HR, 1.044; p = 0.8992; 95% CI, 0.5116–1.9519, and OS; 98.4% vs 96.4%, HR, 0.963; p = 0.9116; 95% CI, 0.473–1.793). According to breast cancer subtype, in the NSM group, all of the 11 patients (100%) who developed local recurrence in the NSM group was hormone receptor (HR)-positive/HER2-negative breast cancer. 29 of the 44 patients (65.9%) who developed local recurrence in the SSM group was HR-positive/HER2-negative, 6 patients (13.6%) was HR-negative/HER2-positive, and 7 patients (15.9%) was triple-negative breast cancer. Among patients who had received neoadjuvant chemotherapy, the NSM group (3 of 14 patients, 21.4%) had a trend for higher local recurrence rate than the SSM group 7 of 116 patients (6.0%) (p = 0.0813). However, no local recurrence in the nipple areola complex was observed for the NSM group. In addition, there was no difference of OS between the NSM group (92.9%) and the SSM group (90.5%) (HR, 0.903; p = 0.9943; 95% CI, 0.049-4.739). Conclusions Our results suggested that NSM with immediate reconstruction might be safe as well as SSM for breast cancer with the nipple–tumor distance of >1 cm with respect to their prognosis and local control regardless of breast cancer subtype or invasiveness. Further studies with a large sample size to assess the risk of local recurrence for NSM after neoadjuvant chemotherapy. Citation Format: Yamashita Y, Hayashi N, Nagura N, Kajiura Y, Yoshida A, Takei J, Suzuki K, Tsunoda H, Yamauchi H. Long-term oncologic safety of nipple-sparing mastectomy with immediate reconstruction [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-17.

Background Magnetic resonance imaging (MRI) or ultrasonography (US) alone is limited in the ability to predict the pathologic complete response (pCR) accurately after neoadjuvant chemotherapy (NAC). The aim of the present study was to predict the pCR using MRI combined with second-look US in primary breast cancer patients. Materials and Methods A total of 1274 consecutive primary breast cancer patients who were examined by MRI and second-look US before and after NAC and had undergone breast-conserving surgery from 2004 to 2014 were included. The positive predictive value (PPV) of a clinical complete response (cCR) by MRI alone and MRI plus US was assessed. A CR was defined as no residual invasive carcinoma. The presence of a residual in situ component was also assessed (ypTis). Results Of the 1274 patients, 333 (26.1%) had a pCR (ypT0/is), and 102 (8.0%) had a residual in situ component (ypTis). A cCR was found in 247 patients (19.4%) using MRI alone and in 182 patients (14.3%) using MRI plus US. The PPV for a cCR using MRI alone was 79.4% and the PPV for MRI plus US was 86.8%. The PPV for a cCR by MRI plus US was the greatest at 98.1% in the estrogen receptor-negative (ER−)/human epidermal growth factor receptor-positive (HER2+) group (86.5% in the ER+/HER2+, 83.0% in the ER−/HER2−, and 64.7% in the ER+/HER2− groups). The PPV for residual in situ component was as low as 72.2%. Conclusion Our results have shown that MRI combined with second-look US in predicting for a pCR was useful compared with MRI alone, especially for ER−/HER2+. However, it was difficult to predict for the presence of a residual in situ component. Our ongoing prospective multi-institutional study has shown that adding vacuum-assisted biopsy to MRI plus second-look US is warranted to improve the prediction of pCR for omitting breast surgery.

Aim Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. Methods To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. Results Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23 years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. Conclusions In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction.Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed.The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43).NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype.

The no-touch saphenous vein harvesting technique is considered to be the ideal procedure to achieve the best quality of vein, whereas the endoscopic vein harvesting (EVH) technique is considered to be ideal for decreasing wound complications. We developed a new technique of EVH with perivascular tissue preservation. This procedure was performed by dissecting the immediate anterior and posterior perivascular connective tissues of the saphenous vein followed by cutting approximately 1 cm laterally from the saphenous vein with the use of a harvester (MAQUET Getinge Group, Getinge AB, Göteborg, Sweden). Histopathological examination revealed preserved perivascular tissue and intimal folding.

Background and Aim Endoscopic band ligation (EBL), used for the treatment of colonic diverticular bleeding, has a lower rebleeding rate than endoscopic clipping. However, different devices are used in Japan and the Western countries; no animal studies have been conducted to elucidate the safety of such devices. We compared two EBL devices, the first used in Japan and the second used in Western countries. Methods and Results The Japanese and Western EBL devices were compared by assessing the EBL safety at 40 sites in an animal model with a normal colon that is anatomically similar to the human colon. Macroscopic and pathological examinations were performed to evaluate the layer ligated by the band and the presence of perforation. The findings on day 1 and day 7 after EBL were compared. The ligated layer was the muscularis propria at 39 sites; the layer was not evaluated at one site where the band was unintentionally removed during the endoscopic procedure. Pathologically, there was no perforation at any of the assessed sites. There was no statistical difference in any of the pathological variables between the two devices or between days 1 and 7 after EBL. The total procedure time was significantly shorter with the Western EBL device. Conclusions In this animal study, both evaluated devices were safe for EBL, without differences in the macroscopic and pathological variables after EBL. Ligation of the muscularis propria layer did not result in perforation., We performed endoscopic band ligation (EBL) on colons of pigs using two different EBL devices and compared the macroscopic and pathological findings to evaluate the efficacy and safety of the two EBL devices, the first used in Japan and the second used in Western countries. Our results indicated that both evaluated devices were safe for EBL. A suitable device can be selected according to the patients' clinical condition.

Ampullary neuroendocrine tumors (NETs) are extremely rare, have a high rate of transmural invasion and lymph node metastasis, and are generally recommended for surgery. In contrast, endoscopic papillectomy (EP) for ampullary NET, a low-grade type within the submucosal layer, is feasible and useful to avoid surgery. However, EP for ampullary NET is controversial, there are no consensus guidelines, and international recommendations are lacking. We present the case of a 60-year-old man with an ampullary NET who was successfully treated with EP via a hexagonal snare. Prior to EP, endoscopic ultrasonography, magnetic resonance cholangiopancreatography, and intraductal ultrasonography in endoscopic retrograde cholangiopancreatography were performed to assess for ductal infiltration of the NET. The specimen revealed a low-grade NET measuring 1.0 × 0.8 × 0.7 cm without venous or lymphatic infiltration, which was negative for horizontal and vertical margins. No recurrence was observed over a 12-month follow-up.

Adenocarcinoma with enteroblastic differentiation (ACED) has high malignant potential. It is known as clear-cell adenocarcinoma, which is a special type of adenocarcinomas characterized by primitive intestine-like structures. Although ACED is often encountered in the stomach, it is very rare in the colon and has not been sufficiently reported. ACED has also not been described in the WHO and Japanese Colonic Carcinoma Classification. ACED has biological characteristics of easy metastasis and a poor prognosis than these of tubular adenocarcinoma. Therefore, all cases of colonic ACED that have been reported previously required either surgery or chemotherapy. We describe a case of flat-elevated-type and 15 mm in size colonic ACED that was successfully treated with endoscopic submucosal dissection. We report our case along with a relevant literature review.

This study assessed the diagnostic accuracy of ultrasound in detecting axillary lymph node metastases in women with breast cancer and atopic dermatitis. We retrospectively reviewed the records of 91 breast cancer patients with a history of atopic dermatitis and compared the dimensions of the lymph nodes on ultrasonographic images of women with and without lymph node metastases diagnosed using histology. Using a major-axis length of ≥5 mm, a short-axis length of ≥5 mm and a cortical thickness of ≥2.3 mm as the criteria for diagnosing axillary lymph node metastases, the specificity was 12.7%, 41.3% and 58.7%, respectively. The low specificity of the ultrasound criteria makes ultrasound unsuitable for diagnosing axillary lymph nodes metastases in breast cancer patients with atopic dermatitis.

Neoadjuvant chemotherapy (NAC) is standard therapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer (HER2 + ve BC). There are concerns about the accurate imaging modalities to measure residual tumor during or after NAC. Up to now no standard imaging method for monitoring the efficacy of NAC has been established, and few reports showed ultrasonographic change. We aimed to assess the echogenicity in ultrasonography (US) as the predictive marker of pathological complete response (pCR) for not only TNBC, but also HER2 + ve BC. Furthermore, we also investigated the change in depth (D) and width (W) of the tumor as the predictive value of pCR. We retrospectively reviewed a consecutive 59 patients with TNBC and 41 patients with HER2 + ve BC who received NAC. In all of 100 patients, echogenicity, D and W of the tumor were measured before (pre-NAC) and after NAC (post-NAC). The tumor echogenicity was measured at representative region of interest (ROI), and calculated as the relative comparative assessment with fat echogenicity (ROI ratio). pCR was significantly associated with higher post-NAC ROI ratio in TNBC (p = 0.010), while there was no association in HER2 + ve BC (p = 0.885). pCR was significantly associated with smaller sizes of post-NAC D and W in TNBC (p = 0.001, 0.003), while no trend was observed in HER2 + ve BC (p = 0.259, 0.435). The area under the curve (AUC) for post-NAC ROI ratio and D were 0.701, 0.755, respectively. Combined with them, AUC became higher up to 0.762. TNBC and HER2 + ve BC showed different morphologic features of residual disease. Echogenicity and tumor size after NAC were both useful to predict pCR for TNBC, but not HER2 + ve BC. In future, radiological imaging needs to be analyzed in terms of breast cancer subtypes.

Patients with Helicobacter pylori-naive mucosa may develop a pale, depressed signet ring cell gastric carcinoma or elevated gastric phenotype carcinoma. Almost all signet ring cell carcinomas are of the flat or depressed type, and elevated lesions are rare. We experienced a case of elevated signet ring cell carcinoma with Helicobacter pylori-naive mucosa. Although the lesion needed to be differentiated from nonepithelial tumor, we diagnosed early and treated with endoscopic submucosal dissection. We report our case along with the relevant literature review.

The clinical behavior of multifocal and multicentric breast cancers (MMBCs) is not well characterized. We conducted this study to ascertain whether patients with MMBCs have a worse prognosis than patients with unifocal breast cancers (UBC). The subjects of this retrospective study were 734 consecutive patients who underwent definitive surgery for invasive breast carcinoma at our hospital between January 2004 and December 2006. MMBC was defined as ≥ 2 separate invasive unilateral breast tumors and pathological T stage was redefined based on the sum of the maximum diameter of each tumor. We evaluated disease-free survival (DFS) using the Kaplan–Meier method and Cox proportional hazards models. Of the 734 patients, 136 (18.5%) had MMBC. The pathological T stage of 36 of the patients with MMBC was upstaged by adopting the sum of each focus. MMBC did not have any survival impact, but MMBC upstaged by the modified pathological T stage was associated with worse DFS than non-upstaging MMBC (P = 0.004). Multivariate analysis revealed that upstaging MMBC was an independent factor for poor prognosis and worse DFS (HR 2.757, P = 0.043). MMBC itself may not be predictive of a worse prognosis; however, the sum of the invasive diameters of MMBC might be an important prognostic factor. Further studies are needed to confirm the prognosis associated with MMBC, taking into consideration the biological characteristics of each invasive focus.

Purpose Prophylactic surgery is a preemptive strategy for hereditary breast and ovarian cancer (HBOC). Prophylactic mastectomy (PM) reduces breast cancer risk by > 90%. The aim of our study is to analyze the information of the Japanese pedigrees and to utilize the results for clinical practice. Methods We statistically analyzed records of HBOC registrees who had undergone BRCA1/2 genetic testing at seven medical institutions up until 2016. In the cases of PM, we examined breasts with the use of mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI) before surgery. After PM, the specimens were divided about 1 cm serially and examined in their entirety. Results Of 1527 registrees who underwent BRCA testing, 1125 (73.7%) were negative for BRCA1/2 mutation, 297 (19.5%) were positive for BRCA1/2 mutation (BRCA1/2MUT+), and 105 (6.9%) had uncertain results. To decide whether to undergo total mastectomy vs. breast-conserving surgery (BCS), 370 registrees underwent presurgical genetic testing. During the follow-up period, four new-onset breast cancers were found among the 55 non-affected BRCA carriers. Among the 73 BRCA1/2MUT+ carriers who underwent BCS, 3 were found to have ipsilateral breast cancer. Of 189 BRCA1/2MUT+ carriers with unilateral breast cancer, 8 were found to have contralateral breast cancer. Of 53 PM specimens, 6 (11.3%) were found to have occult breast cancer despite using MMG, US, and MRI. Conclusions Our report showed a relatively higher incidence rate of occult cancer at 11.3% in PM specimens despite thorough pre-operative radiological evaluations, which included a breast MRI. Considering the occult cancer rates and the various pathological methods of our study and published studies, we propose the necessity of a histopathological protocol.

This study aimed to assess their characteristics and clinical course of each histologic type of the behavior of phyllodes tumor (PT). We retrospectively reviewed 124 patients with PTs who underwent surgical treatment from 2003 to 2011. PTs were classified as benign, borderline, and malignant using surgical specimens. The clinicopathological characteristics according to solitary and multiple lesions on ipsilateral breast and histological change after local recurrence were examined. The median patient age was 42 years (range 12–72 years). The final pathologic diagnosis was benign PTs in 95 patients (76.6%), borderline PTs in 21 (16.9%), and malignant PTs in 8 (6.5%). The size of benign PTs [median 4.2 cm (range 1–21 cm)] was significantly smaller than that of malignant PTs [median 11.3 cm (range 6–27 cm)] (p

Introduction The influence of breast cancer (BC) subtype in discrepancies between pathologic complete response (pCR) and complete response by magnetic resonance imaging (MRI-CR) after neoadjuvant chemotherapy (NAC) have not been discussed well. We evaluated the association between BC subtype and pCR or only residual in situ lesion without invasive cancer (pCR/in situ + ) in patients with MRI-CR (positive predictive value [PPV]). Material and Methods From the data of 716 patients with primary BC who were diagnosed with invasive cancer and treated with NAC and then surgery from January 2009 to May 2014 at St. Luke's International Hospital, 180 patients were determined to have MRI-CR by retrospective chart review. BC subtypes at baseline were classified into 6 subtypes, as strong estrogen receptor (ER ++ ), moderately positive ER (ER + ), negative ER (ER − ), and HER2 status expression. Results Three subtypes had PPV (pCR) ≥ 50%: ER − /HER2 + (56.3%, 27/48), ER − /HER2 − (57.6%, 34/59), and ER + /HER2 + (56.2%, 9/16). However, PPV (pCR) for the ER ++ /HER2 − and ER ++ /HER2 + subtypes was ++ /HER2 − subtype, which was significantly low ( P ++ /HER2 − and other subtypes. PPV (pCR/in situ + ) was significantly low at 20.0% in the ER ++ /HER2 − subtype ( P + ) in other subtypes was collectively greater than 60%, and was 91.7% in the ER − /HER2 + subtype. Conclusion We should interpret carefully MRI-CR of NAC to evaluate residual disease for ER ++ /HER2 − BC.

Background Although the prognostic value of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) depends on the intrinsic subtype of breast cancer, it is not clear whether chemosensitivity itself, shown by a decreasing tumor burden after NAC, contributes to improved prognosis in primary breast cancer patients, especially in patients with non-pCR. The aim of this study was to assess the prognostic effect of changes in tumor stage or nodal status after NAC in each primary breast cancer subtype. Patients and Methods We assessed 719 consecutive patients with primary breast cancer who underwent surgical resection after NAC between 2001 and 2010. The patients were divided into 5 subtypes according to their hormone receptor (HR) status, HER2 status, and nuclear grade (NG; 1/2 = low, and 3 = high). Results In patients with HR-positive (HR+)/HER2−/NG-low tumors, regardless of change in tumor size, the loss of node positivity after NAC significantly improved disease-free survival (DFS). In patients with HR+/HER2−/NG-high tumors, achievement of tumor downstaging as well as the loss of node positivity improved their DFS. In patients with HR−/HER2− tumors, tumor downstaging and the loss of node positivity significantly improved DFS, despite a non-pCR. In contrast, in patients with HER2+ tumors, changes in tumor stage or nodal status were not associated with prognosis unless pCR was achieved. Conclusion Our results revealed that changes in tumor stage and nodal status after NAC might be prognostic markers in patients with HR+/HER2−/NG-high tumors or HR−/HER2− tumors, even if there are residual tumors in the breast.

Elf5 is a transcription factor previously shown to be involved in regulating cell differentiation in both normal and pathological breast tissues. Pertinently, Elf5 was reported to interact with the FOXA1 transcription factor, a pivotal regulatory factor in a subset of AR overexpressing triple negative cancer (TNBC) cases. We examined the correlation among AR, FOXA1, and Elf5 expression in a series of TNBC cases. The cases were retrieved from surgical pathological files of Tohoku University Hospital Japan and consisted of 60 cases operated between the year 1999 and 2007. An additional cohort cases of 51 TNBC ductal carcinoma in situ was used to compare invasive and non-invasive TNBC. In our cohort, 47% of all carcinomas were positive for Elf5, with a significantly higher proportion of Elf5 positive cases occurring in the younger age groups (p = 0.0061). Elf5 immunoreactivity was not associated with any other clinicopathological factors examined in this study. However, Elf5 expression was associated with decreased overall and disease-free survival of the patients (Peto–Peto modification of Gehan–Wilcoxon test, OS p = 0.132, DFS p = 0.1 (LI cutoff 10%); OS p = 0.038, DFS p = 0.021 (LI cutoff 50%)). Of particular interest, its effects on survival were more pronounced in the EGFR−/CK5/6− (non-basal surrogate) than the EGFR+ and/or CK5/6+ (basal-surrogate) subtype of TNBC. Elf5 is present in TNBC and its status was significantly correlated with overall survival of the patients. Further studies examining possible interactions between Elf5 and other factors in TNBC could contribute to disentangling TNBC biology.

A 72-year-old man with end-stage renal disease and who was on dialysis was admitted with fever and chills. Two years previously, he had been diagnosed with caseous calcification of the mitral annulus (CCMA). Blood cultures revealed Staphylococcus aureus, and echocardiography revealed vegetation attached to the CCMA lesion, progressing to both the anterior and posterior annulus. Infective endocarditis (IE) was diagnosed and antibiotic (ampicillin) treatment was initiated. Emergent mitral valve replacement was performed after the occurrence of multiple cerebral infarctions. During surgery, we identified vegetation attached to the CCMA lesion. After surgery, the patient showed a good recovery and was discharged. This case demonstrates that IE can be complicated with CCMA.

Chest radiography showed a right posterior mass on the mediastinum of an 84-year-old woman. The mass had been growing gradually for four years. Surgical excision was performed, and a pathological examination found the mass to be consistent with primary synovial sarcoma (SS) of the mediastinum. To our knowledge, this is a rare case in which follow-up imaging was able to be performed over a period of four years. This disease is aggressive, and its early diagnosis is key to achieving a cure. It is important to consider primary SS in the differential diagnosis of a primary intra-thoracic tumor, even if the tumor grows slowly.

Background: Overexpression of Galectin-3 (Gal-3), a β-galactoside binding protein, has been noted in many tumour types but its functional significance and clinical utility in gastric adenocarcinoma (GAC) are not well known. Methods: We studied 184 GAC patients characterised by histologic grade, sub-phenotypes (diffuse vs intestinal), and ethnicity (Asians vs North Americans). Immunohistochemistry was performed to assess the expression of Gal-3 in human GACs and we correlated it to the clinical outcomes. Cell proliferation, invasion, co-immunoprecipitation and kinase activity assays were done in genetically stable Gal-3 overexpressing GC cell lines and the parental counterparts to delineate the mechanisms of action and activity of inhibitors. Results: Most patients were men, Asian, and had a poorly differentiated GAC. Gal-3 was over-expressed in poorly differentiated (P=0.002) tumours and also in diffuse sub-phenotype (P=0.02). Gal-3 overexpression was associated with shorter overall survival (OS; P=0.026) in all patients. Although, Gal-3 over-expression was not prognostic in the Asian cohort (P=0.337), it was highly prognostic in the North American cohort (P=0.001). In a multivariate analysis, Gal-3 (P=0.001) and N-stage (P=

The purpose of this study was to describe the imaging characteristics of subcutaneous amyloid deposits occurring at sites of insulin injection, commonly known as “insulin balls,” in diabetic patients on ultrasound, CT, and MRI with pathologic correlation. We retrospectively reviewed the radiographic findings of 14 lesions in 9 patients diagnosed with subcutaneous amyloid deposits at our institution between 2005–2015. Three board-certified radiologists analyzed the following: (1) the shape, size, margin, morphologic characteristics, and blood flow on US using the color Doppler signal, (2) shape, size, margin, attenuation, and presence or absence of contrast enhancement on CT, and (3) shape, size, margin, signal intensity, and presence or absence of contrast enhancement on MRI. All lesions showed ill-defined hypovascular subcutaneous nodules with irregular margins. The median diameter of lesions was 50.4 mm on US, 46.8 mm on CT, and 51.4 mm on MRI. The internal echogenicity of subcutaneous amyloid deposits was hypoechoic and heterogeneous on US. All lesions showed isodensity compared to muscle with irregular margins and minimal contrast enhancement on CT. Both T1- and T2-weighted MR images showed low signal intensity compared with subcutaneous fat. Normal diffusion and minimal contrast enhancement were seen. Subcutaneous amyloid deposits which cause insulin resistance are typically ill-defined and heterogeneous hypovascular subcutaneous nodules with irregular margins on imaging that correspond to insulin injection sites. It is also characteristic that T2WI shows low intensity compared with fat on MRI, reflective of the amyloid content.

Background We aimed to assess change in HER2 status after neoadjuvant chemotherapy (NAC) in patients with primary breast cancer and the prognostic impact of such changes. Patients and methods The study comprised 588 patients with a non-pathologic complete response who received anthracycline and/or taxane-based regimens in NAC setting. HER2 status was assessed before NAC and in residual invasive tumor of the surgical specimens. The associations between the change in HER2 status and clinicopathological factors were assessed. Results Before NAC, 489 (83%) of the 588 patients had HER2-negative tumors and 99 patients (17%) had HER2-positive tumors. Eleven (2.2%) of the HER2-negative tumors changed to HER2-positive, while 33 (33%) of the HER2-positive tumors changed to HER2-negative. ER and PR-positivity before NAC were associated with loss of HER2-positivity, whereas receiving trastuzumab was not. In terms of disease-free survival, there was no difference between patients with and those without change in HER2 status after NAC in either the patients with HER2-negative tumors (P = 0.26) or with HER2-positive tumors before NAC (P = 0.23). Conclusion Our results showed that changes in HER2 status did not affect patients' prognosis. Further studies are needed to determine whether HER2-targeting agents can be omitted when loss of HER2-positivity is confirmed after NAC.

Background Familial gastrointestinal stromal tumor (GIST) is a rare disease with germline mutations in the c-kit gene (KIT) or platelet-derived growth factor receptor alpha gene (PDGFRA). We had encountered multiple GISTs in the stomach and small intestine during a screening of ovarian cancer for a woman with hereditary breast and ovarian cancer syndrome (HBOC) with breast cancer susceptibility gene II (BRCA2) mutations. The aim of this study was to examine this case in detail. Case report A 65-year-old woman diagnosed with HBOC harboring BRCA2 mutations was found to have multiple tumors in the stomach and small intestine by abdominal screening. All tumors were resected, and KIT gene mutations (p.Trp557Leu and p.Lys558Glu) in exon 11 were detected in all tumors and peripheral blood leukocytes. The patient was diagnosed with familial GIST. Conclusion This was an extremely rare case in which familial GIST with germline KIT gene mutations co-existed with HBOC.

Aim Lymphocyte predominant breast cancer (BC) is associated with higher pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome in triple negative breast cancer (TNBC) and HER2+ BC. The predictive and prognostic impact of stromal tumour-infiltrating lymphocytes (TILs) after NAT and the change of TILs before (pre-) and after (post-) NAT are not well studied. We aimed to assess the predictive and prognostic value of pre- and post-NAT TILs, as well as their pharmacodynamics modulation and their change for TNBC and HER2+ BC. Materials and methods Two-hundred and nine consecutive patients (n = 80 TNBC, n = 129 HER2+ BC) who received NAT between 2001 and 2009 in a single institution were included. We evaluated the association between pre-NAT TILs and pCR, and the association between pre- and post-NAT TILs, as well as their immunodynamics change with relapse-free survival (RFS) for patients with residual disease (RD). Results Low pre-NAT TILs compared to int/high were significantly associated with lower pCR rate (TNBC: 4.0% vs 43.6%; HER2+ BC: 26.0% vs 51.9%). The median follow-up period was 98 months. In TNBC with RD, low pre-NAT TILs showed significant association with shorter RFS (HR = 3.844 [1.190–12.421], p = 0.024) in multivariate analysis. Low post-NAT TILs showed borderline significant association with shorter RFS (HR = 2.836 [0.951–8.457], p = 0.061). The change in TILs was not associated with RFS. In HER2+ BC, low pre-NAT TILs were not associated with RFS. Conclusion In TN and HER2+ BCs, low pre-NAT TILs tumours had a low likelihood of achieving pCR. In TNBC with RD, both low pre- and post-NAT TILs were associated with shorter RFS. These results suggest that TILs information should be taken into account when additional therapies may be given in the post-neoadjuvant setting.

Background Axillary lymph node (LN) dissection after neoadjuvant chemotherapy (NAC) still remains a standard treatment of initially LN-positive primary breast cancer because of the difficulty of assessment of LN status. The aim of this study was to assess the LN status after NAC in initially LN-positive primary breast cancer patients who were assessed as clinically LN-negative after NAC (ycN0) and identify factors associated with loss of LN metastasis. Patients and Methods The study cohort comprised 279 patients with cytology-proven LN-positivity before NAC. LN status was assessed by ultrasonography. Regional recurrence-free survival and overall survival according to pathologic LN after NAC (ypN) status were assessed in patients with ycN0. Results Of the 279 patients, 179 patients (64.2%) had ycN0. High nuclear grade, estrogen receptor-negative (ER−), and human epidermal growth factor receptor 2-positive (HER2+), were significant predictors of ycN0/ypN0 (P Conclusions Three or more residual LN metastases were rare in patients with ER− tumors if assessed as ycN0 by ultrasonography. Prospective studies are needed to confirm the prognostic impact of not performing axillary lymph node dissection in such patients.

Background: It is not known which population of estrogen receptor (ER)-positive breast cancer patients should continue endocrine treatment beyond 5 years to overcome late recurrences. The aim of this study was to examine a combination of nuclear grade (NG) and expression level of ER and progesterone receptor (PR) to predict late recurrences. Methods: We assessed retrospectively 1677 consecutive ER-positive/HER2-negative patients who underwent surgical resection between 2004 and 2009. Patients with T2 or larger tumor and/or node-positive received pre- or postoperative chemotherapy following the international consensus panel from the St Gallen Conference, 2003. All patients had received adjuvant endocrine treatment. NG, ER and PR statuses were determined by immunohistochemistory on surgical specimen. We classified the patients into 3 groups as follows; ER-high (+++ or Allred score 7, 8)/PR-high (++ to +++ or 5-8) (n=212), ER-high / PR-low (- to + or 3-6) (n=208), and ER-low (+ to ++ or 3-6) / PR-any (n=255). We compared distant disease-free survival (DDFS) in each cohort based on the NG (1:low, and 2 or 3: high). Results: A median follow-up period was 77.0 months. Four hundred sixty seven patients (27.8%) received neoadjuvant chemotherapy, 208 patients (12.4%) received adjuvant chemotherapy, and 1002 patients (59.8%) did not received chemotherapy. Of the 467 patients with neoadjuvant chemotherapy, 65 patients (13.9%) had developed distant metastasis during study period (before 5 years in 51 (11.0%); and after 5 years in 14 (3.0%)). NG-low had significantly higher risk of late recurrence after 5 years than that of NG-high (p=0.005). According to hormonal receptor expression levels, in patients with NG-low, ER-low/PR-any had significantly higher overall DDFS rate than ER-high/PR-low (p=0.016). A similar trend was found before 5 years (p=0.077). However, ER-high/PR-high turned to have significantly high risk of recurrence after 5 years compared to ER-low/PR-any (p=0.024). Of the 208 patients with adjuvant chemotherapy, 16 patients (7.6%) had developed distant metastasis during study period (before 5 years in 5 (2.4%), and after 5 years in 11 (5.2%)). there was no association between a risk of recurrence and hormone receptor statuses at any study period. In the patients did not received chemotherapy, ER-high/PR-high had a trend of higher DDFS rate than others before 5 years (p=0.067). Of the 1002 patients without chemotherapy, only 36 patients (3.6%) had developed distant metastasis during study period (before 5 years in 27 (2.7%), and after 5 years in 9 (0.9%)). There was no difference of late recurrence after 5 years among the patients regardless of ER and PR expression level and NG with only low recurrence rate (0.9%). Conclusions: Our results demonstrated that, in ER-positive/HER2-negative patients who underwent neoadjuvant chemotherapy, NG-low/ER-high/PR-high should receive extend hormonal treatment over 5 years because of the high risk of late recurrence but NG-high/ER-high might not need. Furthermore, patients with T1 and node-negative may not need extend hormonal treatment because of the extremely low risk of late recurrence regardless of NG and hormone receptor statuses. Citation Format: Iwase M, Hayashi N, Yoshida A, Kajiura Y, Takahashi Y, Takei J, Suzuki K, Nakamura S, Yamauchi H. Hormone receptor expression level and nuclear grade associated with late recurrence in estrogen receptor-positive breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-12.

Although undifferentiated adenocarcinomas and fundic gland-type carcinomas are known as Helicobacter pylori-naive gastric carcinomas, well-differentiated gastric phenotype adenocarcinomas with papillary growth are rare. We encountered a case of a rapidly growing pedunculated well-differentiated adenocarcinoma in a patient with a H. pylori-naive gastric mucosa. The tumor had characteristics of a gastric phenotype (pepsinogen I and H and K-adenosine triphosphatase staining negative; diffusely positive for both mucin-5AC [MUC-5AC] and MUC-6; and MUC-2, common acute lymphocytic leukemia antigen 10 [CD-10], and p53 negative) and treated with endoscopic mucosal resection. We report our case along with a relevant literature review.

An eight-year-old girl with myelodysplastic syndrome (refractory cytopenia) received a bone marrow transplant (BMT) from an unrelated donor because of immunosuppressive therapy failure. Following administration of foscarnet for cytomegalovirus reactivation at day40 post-BMT, serum creatinine increased, and proteinuria, hematuria, and hypertension gradually exacerbated and became prolonged. However, neither schistocytosis nor other organ damage was evident. At six months post-BMT, renal biopsy revealed diffuse glomerular damage with glomerular lobulation, a double contour of the glomerular basement membrane, erythrocyte congestion and thrombi in the glomerular endocapillaries, and mesangiolysis, confirming the diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA). We initiated strict controls regarding fluid balance, salt intake, and blood pressure. The patient's renal function improved 10 months post-BMT. TA-TMA often presents as non-specific symptoms, making diagnosis difficult. In cases of post-transplant renal damage, TA-TMA should be differentiated regardless of whether specific symptoms such as hemolytic anemia and other organ failure are evident, and a renal biopsy should, therefore, be considered.