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Background: B7-H4 and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. However, the category of patients wherein these factors are highly expressed and how they are related to each other and programmed cell death ligand 1 (PD-L1) are not yet fully clear. Methods: Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of triple-negative breast cancer (TNBC). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression. The tumor immune microenvironment was evaluated based on stromal tumor-infiltrating lymphocytes (sTILs) (%), pattern classification of TILs, tumor stromal ratio, and tertiary lymphoid structure. Immunostaining for CD8 and FOXP3 was also performed. Results: B7-H4 expression was significantly high in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28-8) (p = 0.021). The H-scores of AR and B7-H4 were inversely correlated (ρ = -0.509, p < 0.001). AR expression was high in cases with IDO1 < 1% (p = 0.046), while B7H4 and IDO1 expression levels were inversely correlated in cases with AR Conclusions: In the population of TNBC, B7-H4 and PD-L1 expression were exclusively related to AR expression.B7-H4 and IDO1 expression was exclusive in the non-luminal androgen receptor subtype of TNBC. These trends in expression may help in the future selection of antiandrogenic agents and immune checkpoint inhibitors for patient treatment.

Background: Human papillomavirus (HPV)-associated oropharyngeal cancer occasionally has a poor prognosis, making prognostic risk stratification crucial. Protease-activated receptor-1 (PAR1) is involved in carcinogenesis and is regulated by alpha-arrestin domain-containing protein 3 (ARRDC3). It is also involved in the tumor microenvironment. We sought to evaluate the predictive ability of PAR1, ARRDC3, and tumor-infiltrating lymphocyte (TIL) scores in patients with oropharyngeal, hypopharyngeal, and uterine cervical cancers, serving as comparators for HPV-associated oropharyngeal cancer. Methods: Immunohistochemical analysis of p16, ARRDC3, and PAR1 expression was performed for 79 oropharyngeal, 44 hypopharyngeal, and 42 uterine cervical cancer samples. The TIL scores were assessed and classified into the following groups based on invasion: Low: 0 %–10 %, Medium: 20 %–40 %, and high: >50 %. For prognostic analysis, the three groups were evaluated by dividing them into low, medium, and high categories, or alternatively into two groups using the median value as the cutoff. Results: p16 was expressed in 44 (56 %) oropharyngeal, 8 (18 %) hypopharyngeal, and all uterine cervical cancer samples. ARRDC3 was detected in 39 (49 %) oropharyngeal, 25 (57 %) hypopharyngeal, and 23 (55 %) uterine cervical cancer samples. PAR1 was expressed in 45 (57 %) oropharyngeal, 22 (50 %) hypopharyngeal, and 22 (50 %) uterine cervical cancer samples. Patients diagnosed with p16-positive oropharyngeal cancer had a substantially improved prognosis compared to those diagnosed as p16-negative cases. Compared to the p16-positive cases, the PAR1-negative cases had a considerably improved prognosis compared to the positive cases (disease-specific survival [DSS] and -negative cases (disease-free survival [DFS]). Multivariate analysis revealed that ARRDC3-positive cases had an appreciably better DSS prognosis than patients with p16-negative oropharyngeal cancers.PAR1-positive cases among patients with p16-positive oropharyngeal cancer had a poor prognosis. With respect to DFS, patients with PAR1-positive and p16-negative oropharyngeal cancer had a 35-fold higher recurrence rate than those with PAR1-negative and p16-negative oropharyngeal cancer. Conclusion: Our results suggest that PAR1 expression affects the prognosis and recurrence rate of HPV-associated oropharyngeal cancer.

The main differentials in cases of sudden elevation of hepatic enzyme levels during immunochemotherapy are reactivation of hepatitis B virus or drug-induced liver injury. Here, we report a case of acute liver injury caused by hepatitis E virus (HEV) during chemotherapy for malignant lymphoma, wherein the patient was successfully treated and completed chemotherapy. A 57-year-old woman visited her local doctor because she felt light and tired. The patient underwent lower gastrointestinal endoscopy and was diagnosed with a malignant lymphoma of the small intestine (diffuse large B-cell lymphoma). The patient had a history of oral consumption of undercooked pork liver to improve anemia and was diagnosed with acute hepatitis E. Since the patient responded to chemotherapy, she was treated with single-agent ribavirin while continuing chemotherapy, resulting in a sustained virological response. Even during treatment with immunosuppressive drugs, if appropriate treatment for hepatitis E can be administered, the patient can be fully treated without interruption. The patient was able to complete chemotherapy adequately without interruption of treatment, which was a clinically beneficial result.

A 70-year-old man with the history of diabetes mellitus complained of lower abdominal discomfort. Abdominal ultrasonography revealed a pancreatic mass. Contrast enhanced CT showed a 2.6 cm-enhanced tumor ventral to the pancreatic head. It was diagnosed with a pancreatic neuroendocrine carcinoma(PanNEC-G3)by EUS-FNA. The patient underwent pancreatoduodenectomy with the wedge resection of the portal vein and partial resection of the transverse colon. We administered 6 cycles of adjuvant therapy with CDDP plus CPT-11. With the presentation of lymph node metastases and the local recurrence in the anastomotic site of the transverse colon 15 months after surgery, the patient received carboplatin plus etoposide(CE)therapy. Although local recurrence completely responded to the CE therapy, bone metastases were detected 27 months after surgery. Metastatic lesion did not respond to systemic chemotherapy including gemcitabine plus nab-paclitaxel and nal-IRI plus 5-FU/LV, and the patient eventually died 37 months after the surgery. PanNECs represent for less than 1% of all pancreatic tumor. They are characterized by high malignant potential and short time survival with the reported OS of 8.5 to 21 months. This case served as an important reminder to consider multimodal treatment for PanNEC patients to obtain longer survival.

A 92-year-old Japanese woman presented with a mass in the left breast, and sparganosis was suspected by biopsy of the mass. The mass disappeared once, but it reappeared at the same site one year later. For a definitive diagnosis, the mass was surgically removed, and a sparganum-like worm was detected. The causative agent was confirmed as Spirometra Type I (most probably Spirometra mansoni) by mitochondrial DNA analysis. The serological examination also proved the case as sparganosis. Considering the presence of two Spirometra species (Type I and II) in Asia, particularly Japan, molecular analysis of the causative agents is highly recommended to understand the epidemiology, infection sources, and pathogenicity in humans in both species, if the parasite specimens are available.