Is 18F-fluorodeoxyglucose PET recommended for small lung nodules? CT findings of 18F-fluorodeoxyglucose non-avid lung cancer.

OBJECTIVES: To determine the image characteristics associated with low 18F-FDG (18F-fluorodeoxyglucose) avidity among 8-15 mm solid lung cancer. METHODS: Patients satisfying the following criteria were included: underwent surgery between January 2014 and December 2019 for lung cancer, presented 8-15 mm nodule without measurable ground glass component on preoperative CT, and underwent 18F-FDG PET before resection. Image characteristics, including air bronchogram, concave shape, pleural attachment, and background emphysema, were evaluated by two board-certified radiologists. The Mann-Whitney U test was used to compare maximum standardized uptake (SUVmax) values from 18F-FDG PET images. RESULTS: The analysis included 235 patients. The SUVmax values of lesions with air bronchogram and concave shape were significantly lower than the SUVmax values of lesions without these features (median: 1.55 vs 2.56 and 1.66 vs 2.45, both P < .001), whereas lesions arising from emphysematous lungs had significantly higher SUVmax values than lesions arising from non-emphysematous lungs (2.90 vs 1.69, P < .001). No significant differences were detected between lesions attached and not attached to pleura. The interobserver agreement was almost perfect for air bronchograms and background emphysema (κ = 0.882 and 0.927, respectively), and 89.7% of lesions with air bronchograms and arising from non-emphysematous lungs showed SUVmax values below 2.5. CONCLUSIONS: Among 8-15 mm solid lung cancer, the presence of air bronchograms and concave shape and the absence of background emphysema were associated with low 18F-FDG accumulation. ADVANCES IN KNOWLEDGE: 18F-FDG PET can be misleading in differentiating certain type of small solid lung cancer.

Ovarian Mesonephric-Like Adenocarcinoma With Recurrent Liver Metastases: A Case Report with Analysis of Therapeutic Molecular Targets.

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare cancer subtype. We describe a patient with ovarian MLA wherein liver metastases developed 1 month after surgery. A phenotypic analysis of the tumor was performed to identify molecular therapeutic targets. A 53-year-old woman, without any symptoms, underwent uterine cancer screening. Transvaginal ultrasonography revealed an ovarian mass, and subsequent pelvic magnetic resonance imaging showed a 13 × 10 cm multicystic ovarian lesion with a solid part. No extra ovarian lesions were observed and a staging laparotomy was performed. Pathological examination revealed an MLA of the left ovary (stage IC1). The tumor comprised tumor cells in a tubular pattern with intraluminal eosinophilic material, as well as mixed glandular and papillary, cord-like, and solid patterns. Endometriosis was also observed. Immunohistochemically, the tumor cells were positive for PAX8, GATA3 (focal), TTF1 (focal), and CD10 (luminal) and negative for the estrogen receptor, progesterone receptor, and WT1. One month after surgery, computed tomography revealed multiple liver metastases. Additional immunohistochemistry for therapeutic targets revealed that the tumor cells were weakly positive for human epidermal growth factor receptor 2 (focal; score 1+), pan-tropomyosin receptor kinase-negative, programmed death-ligand 1-negative, and PMS2 and MSH6 intact. The companion homologous recombination deficiency test (MyChoice®) showed homologous recombination repair proficiency. These findings suggest that poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors may not be effective treatment options. A literature review revealed that data on therapeutic targets in MLA are scarce. In summary, we report a patient with ovarian MLA showing an aggressive clinical course and the phenotypic analysis of the tumor may contribute to the identification of therapeutic targets for MLA.

Nodal infiltration in endometrial cancer: a prediction model using best subset regression.

OBJECTIVES: To build preoperative prediction models with and without MRI for regional lymph node metastasis (r-LNM, pelvic and/or para-aortic LNM (PENM/PANM)) and for PANM in endometrial cancer using established risk factors. METHODS: In this retrospective two-center study, 364 patients with endometrial cancer were included: 253 in the model development and 111 in the external validation. For r-LNM and PANM, respectively, best subset regression with ten-time fivefold cross validation was conducted using ten established risk factors (4 clinical and 6 imaging factors). Models with the top 10 percentile of area under the curve (AUC) and with the fewest variables in the model development were subjected to the external validation (11 and 4 candidates, respectively, for r-LNM and PANM). Then, the models with the highest AUC were selected as the final models. Models without MRI findings were developed similarly, assuming the cases where MRI was not available. RESULTS: The final r-LNM model consisted of pelvic lymph node (PEN) ≥ 6 mm, deep myometrial invasion (DMI) on MRI, CA125, para-aortic lymph node (PAN) ≥ 6 mm, and biopsy; PANM model consisted of DMI, PAN, PEN, and CA125 (in order of correlation coefficient ß values). The AUCs were 0.85 (95%CI: 0.77-0.92) and 0.86 (0.75-0.94) for the external validation, respectively. The model without MRI for r-LNM and PANM showed AUC of 0.79 (0.68-0.89) and 0.87 (0.76-0.96), respectively. CONCLUSIONS: The prediction models created by best subset regression with cross validation showed high diagnostic performance for predicting LNM in endometrial cancer, which may avoid unnecessary lymphadenectomies. CLINICAL RELEVANCE STATEMENT: The prediction risks of lymph node metastasis (LNM) and para-aortic LNM can be easily obtained for all patients with endometrial cancer by inputting the conventional clinical information into our models. They help in the decision-making for optimal lymphadenectomy and personalized treatment. KEY POINTS: •Diagnostic performance of lymph node metastases (LNM) in endometrial cancer is low based on size criteria and can be improved by combining with other clinical information. •The optimized logistic regression model for regional LNM consists of lymph node ≥ 6 mm, deep myometrial invasion, cancer antigen-125, and biopsy, showing high diagnostic performance. •Our model predicts the preoperative risk of LNM, which may avoid unnecessary lymphadenectomies.

Optimal Use of Serum Leucine-Rich Alpha-2 Glycoprotein as a Biomarker for Small Bowel Lesions of Crohn's Disease.

Introduction: A large proportion of small bowel lesions in Crohn's disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods: This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a CD activity index >150 and active colonic lesions were excluded. Results: A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval: 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP <3 mg/L (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81) and 0.74 (0.54-0.84), respectively. The cut-off of 16 µg/mL of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00, while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 µg/mL. Conclusion: LRG can accurately detect and/or exclude the small bowel lesions with two cut-off values.

Effects of anti-ulcer drugs on delirium in trauma patients.

OBJECTIVE: Histamine-2 receptor antagonists (H2RAs) may induce a higher risk of developing delirium than proton pump inhibitors (PPIs), but current evidence is insufficient. Therefore, this study aimed to investigate whether anti-ulcer drugs increase delirium risk. METHOD: Data were obtained from the medical records of patients admitted to a hospital due to trauma. We compared the incidence of delirium in patients who received H2RAs and PPIs with that in patients who received no anti-ulcer drugs. RESULTS: A total of 150, 158, and 238 patients received H2RAs, PPIs, and no anti-ulcer drugs, respectively. Delirium incidence was significantly higher in patients who received H2RAs (34.0%) and PPIs (44.9%) than in those who did not receive anti-ulcer drugs (22.3%). Even after adjustment for possible confounding factors, the association between H2RAs and delirium remained (adjusted OR 1.78; 95% CI 1.04-3.05), but that between PPIs and delirium was attenuated (adjusted OR 1.25; 95% CI 0.71-2.23). CONCLUSIONS: Our results show that H2RAs are associated with delirium risk. We replicated findings of a previous data-driven study. Clinicians need to consider the effect of delirium in anti-ulcer drug selection.

Adenoid Basal Carcinoma with Adenoid Cystic Carcinoma Component of the Uterine Cervix: A Case Report and Literature Review.

Adenoid basal carcinoma (ABC) is rare cancer with a favorable prognosis. However, some ABCs are associated with other histological types, such as squamous cell carcinoma. Here, we present a case of a mixed tumor of ABC and adenoid cystic carcinoma (ACC) of the cervix, with a detailed immunohistochemical study and literature review. We describe a case of a 66-year-old woman who underwent cervical cancer screening that led to the detection of a 0.7 cm nodular lesion. Cervical punch biopsies revealed a high-grade squamous intraepithelial lesion. Cervical conization revealed a mixed carcinoma composed of ABC and ACC, showing stromal invasion, lymphovascular invasion, and positive resection margins. Immunohistochemically, the ACC components were positive for KIT and αSMA and negative for NKX3.1. The tumor presented with proficient mismatch repair (MMR) and was negative for HER2, PD-L1, and TRKA (NTRK1). Subsequent radical hysterectomy with pelvic lymph node dissection revealed the presence of residual tumor cells in the cervix. Our literature review identified six similar cases, including one patient who died of disease recurrence. We report a rare tumor comprising both ABC and ACC. Prognostic data on mixed tumors are scarce; however, given the aggressive nature of ACC, attention should be paid to the detection of mixed tumors. Since ABC and ACC histology may overlap, adequate sampling and IHC for detecting ACC would be helpful.

Uterine Leiomyosarcoma Masquerading as a Malignant Perivascular Epithelioid Cell Tumor: A Diagnostic Challenge.

Uterine sarcomas with myomelanocytic differentiation have been reported to be diagnostically challenging. We report a case of uterine leiomyosarcoma with extensive perivascular epithelioid cell tumor (PEComa)-like areas and extrauterine metastases. The patient was a 49-year-old gravida 3 para 2 Japanese woman with no relevant medical history. She noticed a vaginal mass with bleeding. Imaging examination revealed a uterine tumor and multiple liver and lung metastases. The vaginal tumor (3.5 cm) was resected and diagnosed as a malignant PEComa based on morphology and myomelanocytic marker expression. Clinically used targeted sequencing (FoundationOneCDx™) revealed gene alterations in RB1, TP53, and ATRX but not TSC1/2. Despite administration of an mTOR inhibitor, the tumor size increased, and subsequently, hysterectomy was performed to relieve the symptoms. The uterine tumor was composed of conventional leiomyosarcoma showing RB1 loss, wild-type TP53 staining, and retained ATRX expression, as well as adjacent predominant PEComa-like components with RB1 loss, TP53 overexpression, and ATRX loss, identical to the characteristics of the vaginal tumor. In the uterine tumor, both HMB-45 and MITF were weak to moderately positive for approximately 40% of tumor cells while Melan-A was negative. The tumor was finally diagnosed as leiomyosarcoma with PEComa-like features. This case exemplifies the tumorigenesis of diagnostically challenging tumors with myomelanocytic differentiation and demonstrates the importance of integrating multiple types of information, including genomic profiling, in making a correct diagnosis leading to appropriate treatment.

Delirium risk of histamine-2 receptor antagonists and proton pump inhibitors: A study based on the adverse drug event reporting database in Japan.

OBJECTIVE: Although histamine-2 receptor antagonists (H2RAs) have been shown to be more likely to cause delirium than proton pump inhibitors (PPIs), these results were not adjusted for potential confounding factors. Accordingly, we investigated whether H2RAs and PPIs are risk factors for delirium, even when adjusting for other risk factors by analyzing adverse drug event reports compiled in the post-marketing stages of drugs provided by the Japanese regulatory authorities. METHOD: We analyzed 577,431 reports in the Japanese Adverse Drug Event Report database from April 2004 to July 2020. RESULTS: Of all reports analyzed, 2532 described delirium, and 574,899 described other adverse events. Delirium was associated with H2RAs (crude reporting odds ratio, ROR, 4.17; 95% CI, 3.34-5.22) but not PPIs (crude ROR 0.62; 95% CI 0.43-0.90). Even with adjustment for age, sex, history of dementia or depression, and concomitant drugs reported as risk factors for delirium, the use of H2RAs showed a significantly higher adjusted ROR than that of PPIs (H2RAs: adjusted ROR 3.99; 95% CI 3.18-5.01 and PPIs: adjusted ROR 0.58; 95%CI 0.40-0.84). CONCLUSIONS: These results suggest that, from a cognitive perspective, PPIs may be preferable to H2RAs for patients with or at risk for delirium.

Gastric-type cervical adenocarcinoma with squamous differentiation: buried in adenosquamous carcinomas?

Gastric-type adenocarcinoma (GAS) of the cervix is a human papilloma virus (HPV)-independent, aggressive, and chemo-resistant adenocarcinoma. However, although the histopathological features of GAS have been extensively investigated, squamous differentiation has not been mentioned. This study aimed to elucidate the frequency of GAS with squamous differentiation and describe their clinicopathological characteristics. We retrospectively evaluated 78 patients with GAS (n = 13) and adenosquamous carcinoma (n = 65) diagnosed between 2000 and 2020. Two patients with GAS with squamous differentiation were identified. Both tumors showed advanced stage (pT2bN1) and had predominant GAS and merged squamous cell carcinoma components without p16-block positivity and HPV DNA. Gastric-type adenocarcinoma in situ was confirmed in both cases. Some cases of GAS could show squamous differentiation mimicking the usual, HPV-associated, adenosquamous carcinoma. GAS with squamous differentiation is recognized as an HPV-independent cancer.

Magnetic resonance imaging findings in 11 cases of dedifferentiated endometrial carcinoma of the uterus.

PURPOSE: We evaluated magnetic resonance imaging (MRI) findings of dedifferentiated endometrial carcinoma (DEC), comprising undifferentiated carcinoma and low-grade endometrioid carcinoma. MATERIALS AND METHODS: We recruited 11 patients with pathologically proven DEC treated at our institute. We evaluated primary lesion size, location and signal intensity on MRI, and prognosis. MRI and pathological findings were compared in eight resected patients. RESULTS: Primary tumors ranged from 16 to 206 mm in diameter. DEC was located at the endometrium in 9 of the 11 patients; the remaining two patients showed diffuse involvement of the enlarged myometrium. These two patients with diffuse involvement type died within 4 months. Of the eight patients who underwent resection, seven had macroscopic intratumoral hemorrhage and six showed a high signal on T1-weighted images or low signal on T2-weighted images. Of the eight resected patients, four had tumor necrosis > 25% and tumor size > 5 cm. In these patients, necrosis appeared as nonenhanced areas on contrast-enhanced MRI. CONCLUSION: MRI findings of DEC showed two patterns: mass-forming type and diffuse myometrial type with poor prognosis. Most patients with DEC had intratumoral hemorrhage, and large tumors (> 5 cm) had gross necrosis, which appeared as nonenhanced areas on contrast-enhanced MRI.

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BACKGROUND: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation. CASE PRESENTATION: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation. CONCLUSIONS: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.

Combination of colonoscopy and magnetic resonance enterography is more useful for clinical decision making than colonoscopy alone in patients with complicated Crohn's disease.

BACKGROUND/AIMS: The small bowel is affected in more than half of patients with Crohn's disease (CD) at the time of diagnosis, and small bowel involvement has a negative impact on the long-term outcome. Many patients reportedly have active lesions in the small intestine even in patients in clinical remission. This study was performed to compare findings of magnetic resonance enterography (MRE) and ileocolonoscopy. METHODS: A single-center retrospective study was conducted in 50 patients (60 imaging series) with CD, for whom MRE was additionally performed during the bowel preparation for subsequent ileocolonoscopy. Endoscopic remission was defined as a Simple Endoscopic Score for CD (SES-CD) of <5. MRE remission was defined as a Magnetic Resonance Index of Activity (MaRIA) score of <50. The time to treatment escalation was assessed by the log-rank test. RESULTS: Importantly, 7 of 29 patients (24.1%) with endoscopic remission had a MaRIA score of ≥50. Both SES-CD and MaRIA correlated with the need for treatment escalation (P = 0.025, P = 0.009, respectively). MRE predicted the need for treatment escalation even in patients with endoscopic remission. Although no correlation was present between SES-CD and MaRIA score in patients with structuring/penetrating disease, or insufficient ileal insertion (<10cm), a high MaRIA score still correlated with the need for treatment escalation in stricturing or penetrating disease (P = 0.0306). CONCLUSIONS: The MaRIA score predicts the need for treatment escalation even in patients with endoscopic remission, indicating that addition of MRE to conventional ileocolonoscopy alone can be a useful, noninvasive tool for monitoring CD especially in stricturing or penetrating disease.

Bacterial Expression of a Single-Chain Variable Fragment (scFv) Antibody against Ganoderic Acid A: A Cost-Effective Approach for Quantitative Analysis Using the scFv-Based Enzyme-Linked Immunosorbent Assay.

Due to the highly specific binding between an antibody and its target, superior analytical performances was obtained by immunoassays for phytochemical analysis over conventional chromatographic techniques. Here, we describe a simple method for producing a functional single-chain variable fragment (scFv) antibody against ganoderic acid A (GAA), a pharmacologically active metabolite from Ganoderma lingzhi. The Escherichia coli BL21(DE3) strain produced a large amount of anti-GAA scFv. However, in vitro refolding steps, which partially recovered the reactivity of the scFv, were required. Interestingly, the functional scFv was expressed as a soluble and active form in the cytoplasm of an engineered E. coli SHuffle® strain. Purified anti-GAA scFv, which yielded 2.56 mg from 1 L of culture medium, was obtained from simple and inexpensive procedures for expression and purification. The anti-GAA scFv-based indirect competitive enzyme-linked immunosorbent assay (icELISA) exhibited high sensitivity (linearity: 0.078-1.25 µg/mL) with precision (CV: ≤6.20%) and reliability (recovery: 100.1-101.8%) for GAA determination. In summary, the approach described here is an inexpensive, simple, and efficient expression system that extends the application of anti-GAA scFv-based immunoassays. In addition, when in vitro refolding steps can be skipped, the cost and complexity of scFv antibody production can be minimized.

Immunochromatographic strip assay for detection of bioactive Ganoderma triterpenoid, ganoderic acid A in Ganoderma lingzhi.

Ganoderic acid A (GAA) is one of the major Ganoderma triterpenes produced by medicinal mushroom belonging to the genus Ganoderma (Ganodermataceae). Due to its interesting pharmacological activities, Ganoderma species have been traditionally used in China for the treatment of various diseases. Herein, we developed a colloidal gold-based immunochromatographic strip assay (ICA) for the rapid detection of GAA using highly specific monoclonal antibody against GAA (MAb 12A) conjugated with gold nanoparticles. Using the developed ICA, the detection of GAA can be completed within 15min after dipping the test strip into an analyte solution with the limit of detection (LOD) for GAA of ~500ng/mL. In addition, this system makes it possible to perform a semi-quantitative analysis of GAA in Ganoderma lingzhi, where high reliability was evaluated by enzyme-linked immunosorbent assay (ELISA). The newly developed ICA can potentially be applied to the standardization of Ganoderma using GAA as an index because GAA is major triterpenoid present much in the mushroom.