Prognostic impact of tumor-associated neutrophils in breast cancer.

OBJECTIVES: Neutrophils are the most common type of leukocyte in mammals and play an essential role in the innate immune system and anti-cancer responses. However, recent studies identified the presence of tumor-associated neutrophils (TANs) as a poor prognostic factor. The present study investigated whether relationships exist between TANs and the clinicopathological factors and genetic status of breast cancer. METHODS: A total of 196 breast cancer patients with sufficient biopsy, breast-conserving surgery, or mastectomy specimens between 2014 and 2021 in Hokuto Hospital were included. RESULTS: TANs were individually counted in the tumor stroma (TS) and tumor nest (TN). A higher density of TANs in both TS and TN correlated with tumor size (TS P = 0.010; TN P = 0.001), a high histological grade (TS P < 0.001; TN P < 0.001), the histological type (TS P = 0.009; TN P = 0.034), a high ratio of lymph node metastasis (TS P < 0.001; TN P < 0.001), an advanced stage of cancer (TS P < 0.001; TN P = 0.002), intrinsic subtypes (TS P < 0.001; TN P < 0.001), ERBB2 (TS P < 0.001; TN P < 0.001), MAP3K1 (TS P = 0.002; TN P = 0.023), and TP53 (TS P < 0.001; TN P < 0.001). A higher density of TANs in TS and TN also correlated with shorter disease-free survival and overall survival (P < 0.001). CONCLUSION: The present results suggest that a higher density of TANs correlates with unfavorable prognostic factors in breast cancer. Further research on clinicopathological and genetic factors associated with TANs in breast cancer is needed.

Potential Usefulness a Coronal View using an Automated Breast Ultrasound System in Detecting Breast Lesions.

Objective: An automated breast ultrasound system (ABUS) combined with screening mammography has increased cancer detection rates; however, supplemental ABUS use has increased recall rates. In this study, we aimed to identify an accurate and efficient method of ABUS interpretation and evaluate the potential usefulness of its coronal view versus the conventional transverse view. Materials and Methods: This retrospective observer study included comprised 114 ABUS cases (40 normal, 35 benign, 39 malignant). Ten physicians from multiple institutions interpreted the anonymized coronal and transverse views independently. The observers scored their confidence in the lesion detection for each case using a continuous scale and recorded reading times for each coronal and transverse view interpretation. Free-response receiver operating characteristic analysis was employed to compare detection accuracies between views; a paired t-test was used to compare the average reading times. Results: Detection accuracy did not differ significantly between the coronal and transverse views (figure of merit=0.740 and 0.745, respectively; p = 0.72). However, the average reading time for the coronal view was significantly shorter than that for the transverse view (149.7 vs. 200.3 seconds per case, p = 0.003). Conclusion: The coronal view obtained with the ABUS was useful for interpretation and associated with significantly shorter reading times compared with the conventional transverse view while maintaining breast lesion detection accuracy.

Diagnostic performance of coronal view in comparison with transverse view of three-dimensional automated breast ultrasound.

BACKGROUND: Automated breast ultrasound (ABUS) is one of the first ultrasound devices which enables the de-coupling of image acquisition and interpretation. Another feature of ABUS is the coronal view, utilizing three-dimensional volume data reconstructed from two-dimensional transverse images acquired automatically. PURPOSE: To assess the diagnostic performance of coronal view interpretation by comparing it with that of the transverse view. MATERIAL AND METHODS: This was a retrospective, multi-case, observer study using a cancer-enriched dataset of ABUS images at a single institution with approval by an Institutional Review Board. The 100 scan datasets selected between October 2014 and January 2017 included 70 non-cancer cases and 30 malignancies. In the present observer study, two experienced physicians provided their confidence levels regarding the malignancy of each of the 100 scan datasets independently. The reading times for interpretation of coronal and transverse views were recorded. RESULTS: Area under the receiver operating characteristic curves for two observers with the transverse view (0.856) was improved by use of the coronal view (0.917, P = 0.036). The average reading times were 140.4 s with the coronal view and 148.5 s with the transverse view per scan dataset (P = 0.246). CONCLUSION: It is conceivable that the accurate use of the coronal view will lead to improvement in diagnostic performance in breast cancer screening, although this needs to be confirmed with a larger prospective study.

A case of clear cell variant of solid-pseudopapillary tumor of the pancreas in an adult male patient.

A clear cell variant of solid-pseudopapillary tumor (SPT) of the pancreas was initially reported in 2006 as a tumor that arose in the pancreatic body and tail in young adults; to date, only 4 cases of this entity have been reported. Here, we present the case of a 58-year-old man with clear cell variant of SPT with distinctive clinicopathologic features. The tumor was well demarcated, was 2.6 cm in size and mostly composed of multivacuolated clear cells with solid growth, and exhibited the characteristic immunohistochemical positivity of ß-catenin in the cytoplasm and nuclei of the neoplastic cells. In contrast to classical SPT with nuclear positivity, this case was negative for E-cadherin. Direct DNA sequencing of exon 3 of ß-catenin gene demonstrated a single amino acid substitution (serine to phenylalanine) in codon 37, which is the phosphorylation site by GSKß and frequently found in classical SPT. Electron microscopy demonstrated enlarged mitochondria and endoplasmic reticulum. Despite the fact that previous cases of clear cell variant of SPT arose mainly in the pancreatic body and tail in female young adults (age, 26-32 years), this case suggested that it is possible for a clear cell variant of SPT to arise in the pancreatic head in a middle-aged man. Because the recognition of the clear cell variant of SPT is important for the appropriate diagnosis of primary pancreatic tumor, the present case with its distinctive characteristics may provide new information for a more profound understanding of the pancreatic SPT.

[A case of liver metastasis of rectal cancer, refractory to previous chemotherapy(5-FU/LV, irinotecan, oxaliplatin) responding to bevacizumab combined with FOLFIRI chemotherapy].

The case was a 69-year-old man with liver metastasis who had relapsed after the resection of rectal cancer. We treated the patient with FOLFIRI+bevacizumab(BV)after the failure of S-1+CPT-11, radiation, UFT/LV, FOLFOX and FOLFIRI regimen. The tumor marker level and accumulation of FDG-PET were rapidly decreased after initiating FOLFIRI+BV. There was no serious adverse event, and a remarkable improvement of QOL was observed. This case suggests that the BV combination regimen is useful even after the failure of FOLFOX and FOLFIRI regimen.

[A case of advanced gastric carcinoma successfully treated with TS-1/CDDP as a neoadjuvant chemotherapy].

We report a patient with gastric carcinoma successfully treated with TS-1/CDDP as a neoadjuvant chemotherapy. The patient was a 72-year-old man who had suffered from general malaise with severe anemia and was diagnosed as type 2 carcinoma, having bulky N2, with suspected invasion of the pancreas. TS-1 (100 mg/day) was administered orally every day for 21 days followed by 14 days rest, and CDDP (20 mg/body) was administered by intravenous infusion at day 8, as one course. He was treated as an outpatient, and two courses of treatment resulted in a marked reduction of the lymphnode metastasis without toxicity. Subsequently, he underwent curative surgery consisting of total gastrectomy with D2 lymph node dissection. TS-1/CDDP therapy is very useful as a neoadjuvant chemotherapy especially for an outpatient until surgery.

Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in human gliomas.

Previous studies demonstrated that the Ras suppressor, RSU-1, localizes to human chromosome 10p13, a region frequently deleted in high grade gliomas, and that RSU-1 expression inhibited the tumorigenesis of a glioblastoma cell line. We have now examined RNA from human glial tumors for RSU-1 expression by RT-PCR using primers for the 5' and 3' ends of the RSU-1 open reading frame. Analysis of the amplified RSU-1 cDNA demonstrated that in addition to the entire 858 bp RSU-1 open reading frame, a shorter 725 bp RSU-1 fragment was amplified as well. Sequencing of this product revealed that it encoded a RSU-1 cDNA product which was missing a single 133 bp internal exon. This exon-deleted product was found in 30% of the high grade gliomas studied and 2/3 oligodendrogliomas, but not in other CNS tumors, bladder or colon tumors or normal tissue. The exon-deleted RSU-1 product was infrequently detected in RNA from human tumor cell lines. Expression of an HA-tagged form of the deleted RSU-1 protein in transfected Cos 1 cells revealed that the protein was unstable, with a half life of less than 1 h, in contrast to the full length HA-tagged Rsu-1 protein which was stable for more than 4 h. These results suggest that the alternative splicing of the RSU-1 RNA to produce the exon-deleted form constitutes a mechanism for reduction or loss of functional Rsu-1. Because the expression of Rsu-1 can inhibit malignant growth of glioblastoma cells, the depletion of Rsu-1, via the production of the alternatively spliced form of RSU-1, may inhibit growth regulation in tumors.