Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination.

BACKGROUND: Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS). METHODS: Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples. RESULTS: At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off. CONCLUSIONS: CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.

Transparency-enhancing technology allows the three-dimensional assessment of esophageal carcinoma obtained by endoscopic submucosal dissection.

BACKGROUND: Although much progress has been made in diagnosis of carcinomas, no established methods have been confirmed to elucidate their morphological features. METHODS: Three-dimensional structure of esophageal carcinomas was assessed using transparency-enhancing technology. Endoscopically resected esophageal squamous cell carcinoma was fluorescently stained, optically cleared using a transparency-enhancing reagent called LUCID, and visualized using laser scanning microscopy. The resulting microscope images were converted to virtual HE images for observation using ImageJ software. RESULTS: Microscopic observation and image editing enabled three-dimensional image reconstruction and conversion to virtual HE images. The structure of abnormal blood vessels in esophageal carcinoma recognized by endoscopy could be observed in the 3 dimensions. Squamous cell carcinoma and normal squamous epithelium could be distinguished in the virtual HE images. CONCLUSIONS: The results suggested that transparency-enhancing technology and virtual HE images may be feasible for clinical application and represent a novel histopathological method for evaluating endoscopically resected specimens.

Prevalence of Viral Frequency-Dependent Infection in Coastal Marine Prokaryotes Revealed Using Monthly Time Series Virome Analysis.

Viruses infecting marine prokaryotes have a large impact on the diversity and dynamics of their hosts. Model systems suggest that viral infection is frequency dependent and constrained by the virus-host encounter rate. However, it is unclear whether frequency-dependent infection is pervasive among the abundant prokaryotic populations with different temporal dynamics. To address this question, we performed a comparison of prokaryotic and viral communities using 16S rRNA amplicon and virome sequencing based on samples collected monthly for 2 years at a Japanese coastal site, Osaka Bay. Concurrent seasonal shifts observed in prokaryotic and viral community dynamics indicated that the abundance of viruses correlated with that of their predicted host phyla (or classes). Cooccurrence network analysis between abundant prokaryotes and viruses revealed 6,423 cooccurring pairs, suggesting a tight coupling of host and viral abundances and their "one-to-many" correspondence. Although stable dominant species, such as SAR11, showed few cooccurring viruses, a fast succession of their viruses suggests that viruses infecting these populations changed continuously. Our results suggest that frequency-dependent viral infection prevails in coastal marine prokaryotes regardless of host taxa and temporal dynamics. IMPORTANCE There is little room for doubt that viral infection is prevalent among abundant marine prokaryotes regardless of their taxa or growth strategy. However, comprehensive evaluations of viral infections in natural prokaryotic communities are still technically difficult. In this study, we examined viral infection in abundant prokaryotes by monitoring the monthly dynamics of prokaryotic and viral communities at a eutrophic coastal site, Osaka Bay. We compared the community dynamics of viruses with those of their putative hosts based on genome-based in silico host prediction. We observed frequent cooccurrence among the predicted virus-host pairs, suggesting that viral infection is prevalent in abundant prokaryotes regardless of their taxa or temporal dynamics. This likely indicates that frequent lysis of the abundant prokaryotes via viral infection has a considerable contribution to the biogeochemical cycling and maintenance of prokaryotic community diversity.

A Case of Pyometra Caused by Achromobacter xylosoxidans and γ-Streptococcus in an Elderly Frail Woman.

Pyometra is an easily overlooked disease with nonspecific symptoms; however, a delayed diagnosis can lead to severe complications. An 80-year-old frail woman presented to our hospital with a chief complaint of persistent fever for 10 days. Her blood tests showed an elevated inflammatory response, and computed tomography showed a 10-cm cystic lesion in the pelvic floor compressing the bladder. A catheter was inserted from the vagina into the uterine cavity, resulting in pus drainage and pyometra diagnosis. A pus culture was subsequently performed, which detected Achromobacter xylosoxidans, a common cause of respiratory tract infections in cystic fibrosis and bloodstream infections, andγ-streptococcus. To the best of our knowledge, this is the first report of pyometra caused by Achromobacter xylosoxidans. The patient was treated with drainage and piperacillin-tazobactam administration. Pyometra is especially prevalent in older women with impaired activities of daily living and dementia. Although fever, lower abdominal pain, and increased discharge may occur, symptoms are often nonspecific, and half of such cases are asymptomatic. Furthermore, delayed diagnosis can lead to perforation of the uterus and consequent pan-peritonitis. Thus, the diagnosis of pyometra should be considered in older women presenting with unknown fever, and imaging studies and gynecological consultation should be requested promptly.

Study of the water structure in poly(methyl methacrylate-block-2-hydroxyethyl methacrylate) and its relationship to platelet adhesion on the copolymer surface.

The water structure and platelet compatibility of poly(methyl methacrylate (MMA)-block-2-hydroxyethyl methacrylate (HEMA)) were investigated. The molecular weight (Mn) of the polyHEMA segment was kept constant (average: 9600), while the Mn of the polyMMA segment was varied from 1340 to 7390. The equilibrium water content of the copolymers was found to be mainly governed by the HEMA content. The water structure in the copolymers was characterized in terms of the amounts of non-freezing and freezing water (abbreviated as Wnf and Wfz, respectively) using differential scanning calorimetry. It was found that the Wnf for the copolymers were higher than those estimated from the Wnf for the HEMA and MMA homopolymers and that the amount of excess non-freezing water depended on the polyMMA segment length. In addition, X-ray diffraction analysis revealed that some of the copolymers had cold-crystallizable water. These facts suggested that the polyMMA segments were involved in determining the water structures in the copolymers. Furthermore, the platelet compatibility of the copolymers was improved as compared to that of the HEMA homopolymer. It was therefore concluded that the platelet compatibility of the copolymer was related to the amount of excess non-freezing water.

Spontaneous uterine rupture at 15 weeks' gestation in a patient with a history of cesarean delivery after removal of shirodkar cerclage.

A pregnant woman presented with acute upper abdominal pain and nausea at 15 weeks' gestation. She had a history of cesarean delivery for abruption after the removal of a Shirodkar cerclage that was placed because of cervical shortening caused by conization. She became pregnant again 14 months later. Ultrasonography revealed no significant findings, and a single intrauterine pregnancy with positive fetal heart activity was confirmed. An intestinal obstruction was suspected because abdominal radiography showed multiple air-fluid levels in the colon. Over the 3 hours following admission, her symptoms gradually worsened, and plain abdominal computed tomography (CT) showed a large hemorrhage in the abdominal cavity, but the uterine wall appeared intact at this time. Subsequently, dynamic CT revealed discontinuity of the uterine muscle layer. During laparotomy, uterine rupture with complete opening of the uterine wall at the site of the previous transverse scar was identified. A dead fetus was located within the amniotic sac in a blood-filled abdominal cavity. She received a total of 10 units of packed red blood cells and 6 units of fresh frozen plasma for the resuscitation. She was discharged on the eighth postoperative day without any complications.