The relationship between ring-type dedicated breast PET and immune microenvironment in early breast cancer.

PURPOSE: 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) is related to the biological parameters and prognosis of breast cancer. However, whether whole-body PET (WBPET) and dedicated breast PET (DbPET) can reflect the tumor microenvironment is unclear. This study investigated the relationship between stromal tumor-infiltrating lymphocytes (TILs) and maximum standardized uptake value (SUVmax) in WBPET and DbPET. METHODS: A total of 125 invasive breast cancers underwent WBPET and ring-type DbPET and resected specimens were pathologically assessed. The impact of SUVmax on the tumor biological parameters and TILs was retrospectively evaluated. SUVmax was classified as high and low relative to the median values (WBPET-SUVmax: 2.2 and DbPET-SUVmax: 6.0). RESULTS: SUVmax correlated with tumor size, nuclear grade, Ki-67 labeling index, and TILs in both WBPET and DbPET (all p < 0.001). In multiple linear regression analysis, tumor size, Ki-67 labeling index, and TILs predicted SUVmax in WBPET and DbPET. The cutoff values of tumor size, Ki-67 labeling index, and TILs predicting high SUVmax were 20 mm, 20%, and 20%, respectively. In multivariate analysis, the predictive factors for high SUVmax were tumor size and Ki-67 labeling index for WBPET and tumor size and TILs for DbPET. High SUVmax in DbPET was related to high numbers of TILs after propensity score matching analysis; however, WBPET was not (p = 0.007 and p = 0.624, respectively). CONCLUSIONS: Both SUVmax values in WBPET and DbPET predicted TIL concentration of the primary breast cancer. In DbPET, SUVmax represented the immune microenvironment after adjusting for tumor biological factors.

Liver fibrosis assessment by FibroScan compared with pathological findings of liver resection specimen in hepatitis C infection.

AIM: FibroScan is a tool for the non-invasive diagnosis of hepatic fibrosis. Previous studies have compared liver stiffness to percutaneous liver biopsy findings, but no study has compared liver stiffness to liver resection specimen findings. The aim of this study was to compare FibroScan measurements to resected liver specimen findings. METHODS: From April 2011 to November 2015, a total of 114 patients with liver tumor and hepatitis C were enrolled. We divided them into two groups, the training set and validation set. Liver stiffness was measured by FibroScan before surgery, and specimens obtained by liver resection were evaluated according to the METAVIR system. RESULTS: Using Spearman's rank correlation analysis, a positive correlation between liver stiffness measurement and liver fibrosis stage was observed (r = 0.786, P ≤ 0.0001). In the training set, the area under receiver operating curves for diagnosis of F ≥ 2 was 0.971 (95% confidence interval, 0.928-1.000; cut-off value, 5.9), for diagnosis of F ≥ 3 was 0.911 (0.825-0.997, 9.8), and for diagnosis of F = 4 was 0.917 (0.849-0.985, 15.5). In the validation set, at a cut-off value of 5.9 kPa, sensitivity, specificity, positive predictive values, and negative predictive values for F ≥ 2 were 95.7%, 0.0%, 97.8%, and 0.0%, respectively, of 9.8 kPa for F ≥ 3 were 86.2%, 52.6%, 73.5%, and 71.4%, and of 15.5 kPa for F = 4 were 100%, 71.8%, 45.0%, and 100%. CONCLUSIONS: The stage of stiffness graded by FibroScan has a good correlation with the liver fibrosis of resected liver specimens. It has the ability to diagnose fibrosis stage non-invasively.

Comparison of visual assessment and image analysis in the evaluation of Ki-67 expression and their prognostic significance in immunohistochemically defined luminal breast carcinoma.

OBJECTIVES: To compare the Ki-67 labeling index value obtained through immunohistochemistry analysis by human examiners to that obtained from computer-assisted image analysis, and to establish a cut-off value for Ki-67 labeling index for each method in luminal B breast carcinoma. METHODS: Immunohistochemistry analysis for Ki-67 was performed on the formalin-fixed, paraffin-embedded tissue samples from 403 patients with primary luminal breast cancers. Whole slide images were obtained using the NanoZoomer (Hamamatsu Photonics, Hamamatsu, Japan) and thoroughly analyzed using the Definiens Tissue Studio version 1.1 (Definiens AG, Munich, Germany) to detect the percentage of positively-stained nuclei of carcinoma cells. RESULTS: Although a significant correlation was found between the Ki-67 labeling index obtained by manual assessment and computer-assisted image analysis (Spearman rank correlation coefficient, P < 0.01), the Ki-67 labeling index value obtained by manual assessment was significantly higher than that obtained by computer-assisted image analysis (Wilcoxon signed rank test, P < 0.0001). Disease-free survival was significantly lower in 403 patients with tumors having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.00001) and visual counting (cut-off value: 28.5%; P < 0.00001). Disease-free survival was also significantly lower in 288 patients who received adjuvant endocrine therapy alone having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.0001) and visual counting (cut-off value: 19.7%, P < 0. 0001). CONCLUSIONS: The Ki-67 labeling index values determined by automated analysis and visual counting could equally predict disease-free survival in patients with luminal B breast carcinoma, including those who received endocrine therapy.

Exploring the Gender and Age Demographics of Patients Treated by Emergency Medical Teams during Disasters.

BACKGROUND: Standardized health-data collection enables effective disaster responses and patient care. Emergency medical teams use the Japan Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED) reporting template to collect patient data. EMTs submit data on treated patients to an EMT coordination cell. The World Health Organization's (WHO) EMT minimum dataset (MDS) offers an international standard for disaster data collection. GOAL: The goal of this study was to analyze age and gender distribution of medical consultations in EMT during disasters. METHODS: Data collected from 2016 to 2020 using the J-SPEED/MDS tools during six disasters in Japan and Mozambique were analyzed. Linear regression with data smoothing via the moving average method was employed to identify trends in medical consultations based on age and gender. RESULTS: 31,056 consultations were recorded: 13,958 in Japan and 17,098 in Mozambique. Women accounted for 56.3% and 55.7% of examinees in Japan and Mozambique, respectively. Children accounted for 6.8% of consultations in Japan and 28.1% in Mozambique. Elders accounted for 1.32 and 1.52 times more consultations than adults in Japan and Mozambique, respectively. CONCLUSIONS: Study findings highlight the importance of considering age-specific healthcare requirements in disaster planning. Real-time data collection tools such as J-SPEED and MDS, which generate both daily reports and raw data for in-depth analysis, facilitate the validation of equitable access to healthcare services, emphasize the specific needs of vulnerable groups, and enable the consideration of cultural preferences to improve healthcare provision by EMTs.

Prognostic Impact of Programmed Death-ligand 1 and Surrounding Immune Status on Stage I Lung Cancer.

BACKGROUND: The programmed death 1/programmed death-ligand 1 (PD-L1) pathway reportedly is as an important factor determining effects of immunotherapy; however, its prognostic impact is controversial, and its association with the surrounding immune microenvironment has not yet been elucidated. PATIENTS AND METHODS: We retrospectively analyzed 126 patients with pathologic stage I non-small-cell lung cancer. Patients with lepidic-dominant adenocarcinoma were excluded. PD-L1 expression was evaluated with immunohistochemistry correlated with clinicopathologic features and surrounding immune microenvironment status, including CD4, CD8, regulatory T cells, and human leukocyte antigen class I. Factors affecting prognosis were assessed by Kaplan-Meier and Cox regression analyses. RESULTS: Twenty-three (18.3%) patients were positive for PD-L1 expression. No significant correlation was observed between PD-L1 expression and the surrounding immune microenvironment status. The PD-L1-positive group had a worse prognosis than the PD-L1-negative group (5-year recurrence-free survival rates, 63.4% vs. 81.0%; P = .061). Among surrounding immune cells, intratumoral CD8 status had the strongest impact on prognosis (P = .12). In the intratumoral CD8-high group, PD-L1 expression demonstrated no significant prognostic impact, whereas in the intratumoral CD8-low group, patients positive for PD-L1 demonstrated a significantly worse prognosis than those negative for PD-L1 (5-year recurrence-free survival rates, 41.7% vs. 78.6%; P = .034). Multivariable Cox regression analysis revealed that 'PD-L1-positive and intratumoral CD8-low' status was an independent prognostic factor (hazard ratio, 3.80; 95% confidence interval, 1.22-10.5; P = .023). CONCLUSIONS: The prognostic impact of the PD-1/PD-L1 pathway may be distinct according to concurrent intratumoral CD8 status.

Extra-axial chordoma of the gingiva.

BACKGROUND: Extra-axial chordomas are exceedingly rare malignant tumours. Herein, we present the first case of an extra-axial chordoma in the gingivae. METHODS AND RESULTS: A 21-year-old man presented with a suspected chordoma in the upper right gingiva. Diagnosis was difficult; however, owing to strong expression of the chordoma marker brachyury, extra-axial chordoma was ultimately diagnosed. The tumour was completely resected without performing a facial incision. To ensure its safety and effectiveness, the surgical procedure was simulated several times before its performance using a three-dimensional (3D) model. Twenty-four months after surgery, the patient remains disease-free. CONCLUSION: A diagnosis of extra-axial chordoma can be confirmed by immunohistochemical staining for brachyury.

Sinusoidal obstruction syndrome post-treatment with trastuzumab emtansine (T-DM1) in advanced breast cancer.

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for use in the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer. Here, we present the cases of two patients with metastatic breast cancer who received T-DM1 monotherapy and developed noncirrhotic portal hypertension (NCPH). Patient 1 presented with ruptured gastric varices at 2 years and 5 months after T-DM1 treatment. Patient 2 presented with intrahepatic portal-hepatic venous shunt at 2 years and 6 months and portal-systemic shunt encephalopathy at 4 years and 11 months after T-DM1 treatment. In both the patients, liver biopsies revealed sinusoidal obstruction syndrome (SOS). T-DM1-induced hepatotoxicity can result from SOS. In long-term administration of T-DM1 the unfavorable events associated with chronic liver circulatory disorder due to SOS, such as NCPH, are concerning.

Detectability of Breast Tumors in Excised Breast Tissues of Total Mastectomy by IR-UWB-Radar-Based Breast Cancer Detector.

The objective of this paper is to investigate the detectability of breast tumors having various histological types in excised breast tissues of total mastectomy. The tumor images measured by a portable impulse-radio-ultra-wideband (IR-UWB)-radar-based breast cancer detector are compared with both pathological images and images of dedicated breast positron emission tomography. It is found that the detector can detect invasive-ductal-carcinomas and extensive intraductal component in the dense breast. The density of the breast has a correlation to the effective permittivity derived from the reconstructed confocal images. The results show that the IR-UWB-radar-based breast cancer detector has a potential as a portable modality for early-stage breast cancer screening.

Novel tumor-infiltrating lymphocytes ultrasonography score based on ultrasonic tissue findings predicts tumor-infiltrating lymphocytes in breast cancer.

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for breast cancer. However, because of tumor tissue heterogeneity, an accurate and simple evaluation method is needed. We determined if preoperative characteristic ultrasonography (US) image findings are predictive of lymphocyte-predominant breast cancer (LPBC). METHODS: We evaluated 191 patients with invasive breast cancer treated by curative surgery between January 2014 and December 2017. Stromal lymphocytes in surgical pathological specimens were evaluated. Fifty-two patients with ≥ 50% stromal TILs were defined as having LPBC. Preoperative US images were examined for indicators of TILs. The US images with characteristic TILs were scored for prediction of LPBC. RESULTS: Shape (more lobulated), internal echo level (weaker), and posterior echoes (stronger) were predictors of LPBC and used to assign the TILs-US scores (0-7 points); the score cutoff for predicting LPBC was 4 points (sensitivity, 0.73; specificity, 0.87; accuracy, 0.83) based on the receiver operating characteristics (ROC) curves (AUC 0.88). Multivariate logistic regression analysis identified nuclear grade (NG), OR 3.4; estrogen receptor (ER), OR 5.7; human epidermal growth factor receptor type-2 (HER2), OR 4.1; and TILs-US score, OR 14.9 as LPBC predictors (all, p < 0.05). The sensitivity, specificity, and accuracy for predicting LPBC were 0.75, 0.69, and 0.71 for NG and 0.33, 0.96, and 0.79 for ER and HER2, respectively. ROC analysis showed that the diagnostic abilities of NG, ER, and HER2 were lower than that of the TILs-US score. CONCLUSIONS: LPBC showed characteristic US imaging findings. The TILs-US score was an accurate preoperative predictor of LPBC.

A case of primary malignant melanoma of the esophagus with a widely expanded surface area.

Primary malignant melanoma of the esophagus (PMME) is rare but aggressive. PMME accounts for approximately 0. 1% of all malignant esophageal neoplasms occurring worldwide, and is usually diagnosed during the advanced stage. A 67-year-old man underwent an esophagogastroduodenoscopy (EGD) at our hospital and confirmed 20 mm of black pigmentation in the lower esophagus in the chest area. Pathological biopsy findings of the black-pigmented epithelial tissue revealed the presence of tumor cells with brown granules, leading to the diagnosis of malignant melanoma. Owing to difficulty in accurately diagnosing the range in this PMME case, we performed thoracoscopic esophagectomy. Pathological organisation test results were pT1a-LPM, INFb, pN0, and pM0, which were diagnosed at pStage I. The lesion expanded extensively, measuring > 10 cm in diameter. The tumor cells, which were centrally located in the black-pigmented area, were observed to have proliferated beyond the surrounding brownish area into the mucosa, but no findings were found in the endoscopic examination. As in this case, because PMME may diffusely spread along the basal layer outside the range of pigmentation, endoscopic diagnosis of the extent of disease spread may be impossible; hence, it is important to keep this phenomenon in mind while performing resection to treat PMME.

Successful Resection of Solitary Abdominal Wall Metastasis of Sarcomatous Intrahepatic Cholangiocarcinoma.

Sarcomatous intrahepatic cholangiocarcinoma (ICC) is a rare histological variant of ICC that is composed of both adenocarcinoma (ICC component) and sarcomatous components. Surgery is believed to be the primary treatment, and some reports describe primary resection. However, due to the aggressive malignancy of sarcomatous ICC, there is no report regarding resection of a metastatic lesion. In this report, we present the case of a 75-year-old woman admitted to our hospital with the chief complaint of weight loss. Various imaging techniques demonstrated a single mass in the liver and cecum. A cecal gastrointestinal stromal tumor accompanied by liver metastasis was suspected, and ileocecal resection was performed for diagnostic purposes. However, the tumor was present in the abdominal wall rather than in the cecum. The tumor was resected and diagnosed as undifferentiated sarcoma. We suspected the liver tumor was a series of lesions, so we performed hepatectomy. As the tumor was composed of both adenocarcinoma and sarcomatous components, it was diagnosed as sarcomatous ICC. The histological findings of the abdominal wall tumor were similar to those of sarcomatous ICC, so we diagnosed the abdominal wall tumor as a solitary metastasis of sarcomatous ICC. In this case, solitary metastasis was observed, and we were able to resect both the primary and metastatic lesions. This case illustrates that when solitary metastasis can be seen in sarcomatous ICC, radical resection is possible.

KRAS fluorescence in situ hybridisation testing for the detection and diagnosis of pancreatic adenocarcinoma.

AIMS: The aim of our study was to analyse correlations between KRAS mutation status, chromosomal changes that affect KRAS status in cells from pancreatic tumours. METHODS: We collected 69 cases of surgically resected pancreatic ductal adenocarcinoma (PDA) and seven cases of chronic pancreatitis (CP). Chromosomal abnormalities of KRAS and CEP12 were detected using fluorescence in situ hybridisation (FISH). RESULTS: The number of CEP12 signals per cell ranged from 1.78 to 2.04 and 1.46 to 4.88 in CP and PDA samples, respectively, while the number of KRAS signals per cell ranged from 1.94 to 2.06 and 1.88 to 8.18 in CP and PDA samples, respectively. The 'chromosomal instability index', which was defined as the percentage of cells with any chromosomal abnormality, was over 5.7 times greater in PDA than in CP. We performed KRAS mutation analysis by direct sequencing and found that tumours with KRAS mutations have a significantly higher mean KRAS signal per cell from PDA samples compared with tumours with wild-type KRAS. KRAS amplification was noted in 10% of cases. Although we found that lymph node metastasis and distal metastasis of PDA were more frequent in cases with KRAS amplification, this was not correlated with overall survival. Using a threshold of 40%, we found that the chromosomal instability index robustly discriminated PDA cells from CP cells. CONCLUSIONS: Based on these findings, we concluded that FISH testing of KRAS using cytology samples may represent an accurate approach for the diagnosis of PDA.

Two Case Reports of Intravenous Leiomyomatosis with Hyaluronan Expression.

Intravenous leiomyomatosis (IVL) is a rare benign neoplasm. Herein, we describe two cases of IVL at different levels of progression. The tumor in Case 1 was extensive, invading the right atrium after a hysterectomy for a uterine myoma. The tumor temporarily responded to hormonal treatment; however, tumor regrowth occurred. In contrast, the tumor in Case 2 extended only to the pelvic veins and was revealed preoperatively. Hysterectomy and bilateral salpingo-oophorectomy were performed, resulting in the complete surgical resection of the tumor. In Case 2, no recurrence has been observed. Tumor samples were evaluated for hyaluronan expression using Alcian blue staining (with and without hyaluronidase digestion). The tumor in Case 1 stained strongly positive for hyaluronan while the tumor in Case 2 stained weakly positive for hyaluronan. In contrast, a large non-IVL uterine leiomyoma (control) stained negative for hyaluronan. These results suggest a relationship between tumor hyaluronan expression and IVL progression, similar to that in other cancers.

Aggressive angiomyxoma of the liver: a case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that occurs almost exclusively in the soft tissue of the pelvis and perineum. AAM has both locally infiltrative and recurrent characteristics. Very few cases of AAM occurring outside of the pelvis and perineum have been reported. Here, we report a case of AAM originating in the liver of a 33-year-old female patient. CASE PRESENTATION: A 33-year-old woman underwent S8 subsegmentectomy after clinical diagnosis of a mucinous cystic neoplasm of the liver. Histological analysis revealed a tumor composed of spindle-shaped cells with vascular proliferation in a myxoid stroma. Immunohistochemically, the tumor cells stained positively for CD34, estrogen receptor (ER), and progesterone receptor (PgR) and negatively for S-100, EMA, CK19, CD99, HMB45, and α-smooth muscle actin. The tumor was diagnosed as AAM originating from the liver. The patient received no adjuvant chemotherapy. No sign of recurrence or distant metastasis has been noted for 10 months after the surgery. CONCLUSIONS: We here report a second case of AAM originating from the liver, which is an uncommon location for this particular tumor.

Utility of cytopathological specimens and an automated image analysis for the evaluation of HER2 status and intratumor heterogeneity in breast carcinoma.

OBJECTIVES: Although updated HER2 testing guidelines have been improved by a collaboration between the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) in 2013, HER2 evaluation is still problematic because of issues involving CEP17 polysomy, heterogeneity, and HER2 score 2+ cases. The aim of this retrospective study was to evaluate the relationship between HER2 gene heterogeneity, or so called CEP17 polysomy, using breast carcinoma cells sampled by scraping and the IHC score graded by automated image analysis using whole slide image. MATERIAL AND METHODS: We randomly selected 23 breast carcinoma cases with a HER2 score 0, 24 cases with a HER2 score 1+, 24 cases with HER2 score 2+, and 23 cases with HER2 score 3+ from the records of patients with breast cancer at Hiroshima University Hospital. We compared the results of fluorescent in situ hybridization (FISH) using formalin-fixed, paraffin-embedded (FFPE) tissues and cytological samples and compared the HER2 score calculated using an automated image analysis using wholly scanned slide images and visual counting. RESULTS: We successfully performed the FISH assay in 78 of 94 cases (83%) using FFPE tissues and in all 94 (100%) cases using cytological samples. Frequency of both HER2 amplification and CEP17 polysomy was higher when cytological samples were used than when FFPE tissue was used. Frequency of HER2 heterogeneity using cytological samples was higher that than using FFPE tissue, except for the IHC score 3+ cases. CONCLUSIONS: When assessment of HER2 status based on FISH using FFPE tissue cannot be accomplished, FISH using cytological samples should be considered. When intensity of HER2 is heterogeneous in the tumor tissue, particularly in cases regarded as score 2+, they should be evaluated by automated image analysis using the whole slide image.