Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Fusion Imaging for Prediction of Metastasis to Sentinel and Nonsentinel Nodes in Patients with Clinically Node-Negative Breast Cancer.

PURPOSE: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) is an important diagnostic tool in breast cancer. The utility of maximum standardized uptake values (SUVmax) of primary tumors has been evaluated to predict sentinel node (SN) and non-SN metastasis in clinically node-negative (cN0) patients. PATIENTS AND METHODS: 18F-FDG PET/CT was performed on 414 cN0 patients. The following parameters were evaluated: SUVmax at 60 min (SUVmax1), SUVmax at 120 min (SUVmax2), percent change between SUVmax1 and SUVmax2 (ΔSUVmax%), SN metastasis foci maximum size (SN meta size), and ratio of metastatic SNs to total SNs or SN ratio (SNR). It was assessed whether these were risk factors for SN metastasis. The relationship between these parameters and the status of SN and/or non-SN metastasis was retrospectively explored to predict non-SN metastasis. RESULTS: All SUV parameters significantly correlated with pathological T factor (pT), nuclear grade, lymphatic invasion (Ly), and Ki-67 labeling index. On multivariate analysis, pT and Ly were independent predictive factors for SN metastasis. In SN meta-positive cases, SN meta size, SNR, and ΔSUVmax% were predictors for non-SN metastasis on univariate analyses, and the former two were independent predictors on multivariate analysis. The combination of SUVmax2 and ΔSUVmax% was an independent predictor of non-SN metastasis (P = 0.0312) and was associated with prediction of non-SN metastasis negative status with high probability (92.3%). CONCLUSIONS: In patients with cN0 breast cancer, SUV parameters of the primary tumor were correlated with pathological features. The combination of SUVmax2 and ΔSUVmax% may be useful for predicting non-SN metastasis.

Dual time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer.

BACKGROUND: To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUVmax) at 60 min (SUVmax1) and SUVmax at 120 min (SUVmax2) (ΔSUVmax%) using dual time point 18F-fluorodeoxyglucose emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer. METHODS: Four hundred and sixty-four patients with primary breast cancer underwent 18F-FDG PET/CT for preoperative staging. ΔSUVmax% was defined as (SUVmax2 - SUVmax1) / SUVmax1 × 100. We explored the optimal cutoff value of SUVmax parameters (SUVmax1 and ΔSUVmax%) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUVmax1 and ΔSUVmax% were analyzed by Cox's univariate and multivariate analyses. RESULTS: The optimal cutoff values of SUVmax1 and ΔSUVmax% were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUVmax1 groups (P = 0.0003) and also between high and low ΔSUVmax% groups (P = 0.0151). In Cox multivariate analysis for RFS, SUVmax1 was an independent prognostic factor (P = 0.0267) but ΔSUVmax% was not (P = 0.152). There was a weak correlation between SUVmax1 and ΔSUVmax% (P < 0.0001, R2 = 0.166). On combining SUVmax1 and ΔSUVmax%, the subgroups of high SUVmax1 and high ΔSUVmax% showed significantly worse prognosis than the other groups in terms of RFS (P = 0.0002). CONCLUSION: Dual time point 18F-FDG PET/CT evaluation can be a useful method for predicting relapse in patients with breast cancer. The combination of SUVmax1 and ΔSUVmax% was able to identify subgroups with worse prognosis more accurately than SUVmax1 alone.

Imatinib plasma levels during successful long-term treatment of metastatic-gastrointestinal stromal tumors.

BACKGROUND/AIMS: To investigate whether imatinib dosage correlated with effective plasma levels and clinical characteristics for Japanese patients undergoing long-term (≥2 years) imatinib therapy for GISTs. METHODOLOGY: Twenty-five patients who received imatinib for a metastatic pathologically diagnosed GISTs at our hospital were enrolled. Imatinib response was assessed according to Choi's criteria. Blood samples were collected 22­26 h after the previous imatinib dose before the next scheduled dose. Results: Fourteen patients were male and the median age was 65 years. The median duration of imatinib therapy was 3.8 years (range, 2.0­11.5 years). The median plasma level of imatinib was 1098 ng/ml and the minimal plasma level after ≥5 years of therapy was 789 ng/ml. Imatinib dosage was significantly correlated with history of gastrectomy. The minimum body surface area of patients who received 400-mg/day imatinib dosage was 1.560 m2. CONCLUSIONS: The minimum level in all patients showing response for ≥5 years of treatment was 789 ng/ml, suggesting an effective plasma imatinib level of ≥800 ng/ml. Our results suggest that imatinib dosage of 400 mg/day is recommended for a patient with a large BSA (≥1.56 m2) and that of 300 mg/day might be sufficient for patients who have undergone a gastrectomy.

Combined multi-kernel head computed tomography images optimized for depicting both brain parenchyma and bone.

BACKGROUND: The hybrid convolution kernel technique for computed tomography (CT) is known to enable the depiction of an image set using different window settings. OBJECTIVE: Our purpose was to decrease the number of artifacts in the hybrid convolution kernel technique for head CT and to determine whether our improved combined multi-kernel head CT images enabled diagnosis as a substitute for both brain (low-pass kernel-reconstructed) and bone (high-pass kernel-reconstructed) images. METHODS: Forty-four patients with nondisplaced skull fractures were included. Our improved multi-kernel images were generated so that pixels of >100 Hounsfield unit in both brain and bone images were composed of CT values of bone images and other pixels were composed of CT values of brain images. Three radiologists compared the improved multi-kernel images with bone images. RESULTS: The improved multi-kernel images and brain images were identically displayed on the brain window settings. All three radiologists agreed that the improved multi-kernel images on the bone window settings were sufficient for diagnosing skull fractures in all patients. CONCLUSIONS: This improved multi-kernel technique has a simple algorithm and is practical for clinical use. Thus, simplified head CT examinations and fewer images that need to be stored can be expected.

Novel nasogastric tube-related criteria for urgent endoscopy in nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Patients with active upper gastrointestinal bleeding (UGIB) require urgent endoscopy, but appropriate criteria for urgent endoscopy in these patients have not yet been established. AIMS: The goal of this study is to establish a simple system for the selection of UGIB patients who may benefit from urgent endoscopy. METHODS: Of the 335 patients who required emergency hospitalization for UGIB from May 2010 to March 2012 at Nagoya Daini Red Cross Hospital, 166 patients who underwent placement of a nasogastric tube (NGT) were retrospectively identified. Active bleeding on the endoscopic image was used as an endpoint that reflected the need for urgent endoscopy. RESULTS: The ratio of the heart rate to the systolic blood pressure (HR/SBP ratio) and aspiration of fresh or dark red fluid from the NGT [NGT(+)] were significant predictors of active bleeding in the univariate analysis [HR/SBP ratio, P=0.016; NGT(+), P<0.001]. The HR/SBP ratio [odds ratio (OR) 8.118; 95% confidence intervals (CI) 1.696-38.850; P=0.009] and NGT(+) (OR 4.630; 95% CI 2.092-10.204; P<0.001) were also significantly associated with active bleeding in the multivariate analysis. Moreover, receiver operating characteristic analysis revealed a setting with HR/SBP ratio>1.4 or NGT(+) to be optimal criteria to predict active bleeding. These criteria were associated with a sensitivity of 64.9% (24/37) and a specificity of 76.7% (99/129) for the prediction of active bleeding; consequently, they are superior to the sensitivity and specificity of previously proposed criteria. CONCLUSIONS: A novel and simple criteria system using NGT(+) and HR/SBP is a good predictor of the need for urgent endoscopy in patients with nonvariceal UGIB.

Vasospasm-induced ST-segment elevation myocardial infarction in a premenopausal woman with endothelial dysfunction.

ST-segment elevation myocardial infarction (STEMI) can be caused by coronary artery vasospasm (VSA) due to endothelial dysfunction. However, the clinical role of endothelial function tests in VSA-induced STEMI is not fully understood. We present the case of a 43-year-old woman with atypical chest pain and no coronary risk factors. STEMI caused by VSA was diagnosed. Flow-mediated vasodilatation (FMD) and EndPAT tests were performed; the FMD and reactive hyperaemia index were 3.8% and 1.23, respectively. Endothelial dysfunction is the putative cause of STEMI. FMD and EndPAT tests might be useful for predicting adverse outcomes in young premenopausal women with VSA.

Delayed Vasovagal Reaction with Reflex Syncope Following COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) has become a pandemic, and vaccines remain the only effective tools available for ending it. However, their side effects, such as syncope, which mimics sudden cardiac death, are serious concerns. We herein report 6 cases of delayed vasovagal syncope and presyncope (VVR) caused by COVID-19 vaccination among 25,530 COVID-19 patients. The prevalence of delayed VVR due to COVID-19 vaccination was 0.026%. In addition, no delayed VVR was found among 17,386 patients who received the influenza vaccine. Delayed VVR is likely to be overlooked if medical staff are not aware of this symptom. This report provides significant information regarding effects of COVID-19 vaccination.

Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation.

AIMS: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. METHODS: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day, n=16) for 12weeks. 18F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. RESULTS: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%). 18F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of 18F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. CONCLUSIONS: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.

IgG4-related Sclerosing Cholangitis Complicated with Cholangiocarcinoma and Detected by Forkhead Box P3 Immunohistochemical Staining.

An 80-year-old man was admitted due to biliary stricture with autoimmune pancreatitis. Although radiographical examinations suggested Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC), punched biopsies from the bile duct revealed adenocarcinoma. In the resected specimen, abundant N-terminus of Forkhead box P3 (Foxp3)-positive cells were localized in cholangiocarcinoma (CCA) tissue, while IgG4-positive cells were spread around the entire bile duct. Therefore, the case was diagnosed with IgG4-SC accompanied by CCA, not sporadic CCA. We herein report an informative case wherein IgG4-positive cells were abundant in CCA tissue and Foxp3 immunohistochemical staining allowed us to determine that this case had two entities.

Variations in atherosclerosis and remodeling patterns in aorta and carotids.

BACKGROUND: Atherosclerosis is a progressive disease that causes vascular remodeling that can be positive or negative. The evolution of arterial wall thickening and changes in lumen size under current "standard of care" in different arterial beds is unclear. The purpose of this study was to examine arterial remodeling and progression/regression of atherosclerosis in aorta and carotid arteries of individuals at risk for atherosclerosis normalized over a 1-year period. METHODS: In this study, 28 patients underwent at least 2 black-blood in vivo cardiovascular magnetic resonance (CMR) scans of aorta and carotids over a one-year period (Mean 17.8 +/- 7.5 months). Clinical risk profiles for atherosclerosis and medications were documented and patients were followed by their referring physicians under current "standard of care" guidelines. Carotid and aortic wall lumen areas were matched across the time-points from cross-sectional images. RESULTS: The wall area increased by 8.67%, 10.64%, and 13.24% per year (carotid artery, thoracic aorta and abdominal aorta respectively, p < 0.001). The lumen area of the abdominal aorta increased by 4.97% per year (p = 0.002), but the carotid artery and thoracic aorta lumen areas did not change significantly. The use of statin therapy did not change the rate of increase of wall area of carotid artery, thoracic and abdominal aorta, but decreased the rate of change of lumen area of carotid artery (-3.08 +/- 11.34 vs. 0.19 +/- 12.91 p < 0.05). CONCLUSIONS: Results of this study of multiple vascular beds indicated that different vascular locations exhibited varying progression of atherosclerosis and remodeling as monitored by CMR.

Impact of oxidative posttranslational modifications of SERCA2 on heart failure exacerbation in young patients with non-ischemic cardiomyopathy: A pilot study.

BACKGROUND: Oxidative posttranslational modifications (OPTM) impair the function of Sarcoplasmic/endoplasmic reticulum (SR) calcium (Ca2+) ATPase (SERCA) 2 and trigger cytosolic Ca2+ dysregulation. We investigated the extent of OPTM of SERCA2 in patients with non-ischemic cardiomyopathy (NICM). METHODS AND RESULTS: Endomyocardial biopsy (EMB) was obtained in 40 consecutive patients with NICM. Total expression and OPTM of SERCA2, including sulfonylation at cysteine-674 (S-SERCA2) and nitration at tyrosine-294/295 (N-SERCA2), were examined by immunohistochemical analysis. S-SERCA2 increased in the presence of late gadolinium enhancement on cardiac magnetic resonance imaging. S-SERCA2/SERCA2 and N-SERCA2/SERCA2 correlated with cardiac fibrosis evaluated by Masson's trichrome staining of EMB. SERCA2 expression modestly increased in parallel with an upward trend in OPTM of SERCA2 with aging. This tendency became prominent only in patients aged >65 years. OPTM of SERCA2 positively correlated with brain natriuretic peptide (BNP) values only in patients aged ≤65 years. Composite major adverse cardiac events (MACE) increased more in the high OPTM group of younger patients; however, MACE-free survival was similar irrespective of the extent of OPTM in older patients. CONCLUSIONS: OPTM of SERCA2 correlate with myocardial fibrosis in NICM. In younger patients, OPTM of SERCA2 correlate with elevated BNP and increased composite MACE.

[Efficacy and safety of S-1 plus docetaxel combination therapy for patients with advanced gastric cancer].

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.

Spontaneous Regression of Germinomas After Salvage Surgery and Possible Mechanism of Induced Apoptosis.

BACKGROUND: A few cases of spontaneous regression of germ cell tumors have been reported. Possible mechanisms include steroid medication, surgical intervention, diagnostic radiation exposure, and immune response. None of these hypotheses has been supported by sufficient data. CASE DESCRIPTION: Two cases of germinoma demonstrated spontaneous regression before antitumor therapy. In the first case, a 19-year-old man presented with acute hydrocephalus due to a pineal mass and underwent emergent endoscopic third ventriculostomy. The pineal tumor started to regress on the 4th postoperative day after endoscopic third ventriculostomy. In the second case, a 22-year-old man presented with acute hydrocephalus and panhypopituitarism due to a suprasellar mass and underwent emergent external ventricular drainage, biopsy, and septostomy on the day of admission. Apparent regression of the tumor was discovered on the 5th day after initial surgery. Pathologic diagnosis was pure germinoma in both cases. Remarkable accumulations of CD4-positive lymphocytes and some apoptotic cells positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining were detected in both cases. Diagnostic radiation exposure is the only common condition in all reported cases. CONCLUSIONS: This unusual phenomenon of spontaneous regression of germinoma may be caused by a combination of pathognomonic characteristics of anatomic location with paraventricular development and stress induction as a trigger, such as salvage surgery or diagnostic radiation, including at extremely low dosage.

Perivascular Epithelial Cell Tumor of the Pancreas Diagnosed Preoperatively by Endoscopic Ultrasound-guided Fine-needle Aspiration.

We herein report a 49-year-old woman with a perivascular epithelial cell tumor (PEComa) of the pancreas. Imaging studies demonstrated a relatively well-demarcated mass, measuring approximately 40 mm in diameter, located in the pancreatic tail. It was heterogeneously enhanced almost to the same degree as the surrounding pancreatic tissue in both the arterial and portal venous phases. We performed endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using the Acquire® 22-gauge needle and preoperatively obtained a definitive diagnosis with a sufficient sample. Clinicians should consider pancreatic PEComa in their differential diagnosis of patients with a pancreatic mass.

Inhibitory Effect of TNF-alpha Produced by Macrophages Stimulated with Grifola frondosa Extract (ME) on the Growth of Influenza A/Aichi/2/68 Virus in MDCK Cells.

We investigated the inhibitory effect of the conditioned medium (CM) from P338D1 (D1) cells, a murine macrophage cell line, stimulated for 10 hours with a fixed dose (100 mug/ml) of the extracts from the fruit bodies of Grifola frondosa (ME) or its ultra filtration-based fractions (MFs), on the growth of influenza A/Aichi/2/68 virus in Madin-Darby canine kidney cells. Direct addition of ME and 3 kinds of MFs (MF1, MF2 and MF3) to the infected cells had no obvious inhibitory effect. However, virus yields were reduced in the presence of CMs. Notably, the inhibitory effect of the CM prepared by using MF2 (molecular weight of 30 Kd to 100 Kd) was the strongest (28% reduction compared to the control). RT-PCR and ELISA assays showed that the CMs could induce the expression of TNF-alpha mRNA in D1 cells leading to production of TNF-alpha, known as an antiviral cytokine. These findings suggest that ME and MFs (especially MF-2) might induce the production of certain factors, including TNF-alpha, which are responsible for the inhibition of viral growth in vitro.

Clinical significance of the serum IL-2R level and Ga-67 scan findings in making a differential diagnosis between sarcoidosis and non-Hodgkin's lymphoma.

OBJECTIVE: To compare the serum-soluble interleukin-2 receptor (sIL-2R) levels of non-Hodgkin's lymphoma patients and active sarcoidosis patients in relation to the (67)Ga scan findings. METHODS: A total of 29 adenopathy patients suspected of having non-Hodgkin's lymphoma or sarcoidosis were enrolled in the study. All patients underwent a whole-body (67)Ga scan and single-photon emission computed tomography studies 48 h after intravenous injection of (67)Ga citrate. The sIL-2R levels were compared between the sarcoidosis patients and non-Hodgkin's lymphoma patients, the patients with and without the panda and/or lambda sign, the lymphoma patients with stage I/II disease and with stage III/IV disease, and the sarcoidosis patients and non-Hodgkin's lymphoma patients with stage III/IV disease. RESULTS: The range of the sIL-2R levels was 195-3750 U/ml in sarcoidosis and 240-62 300 U/ml in non-Hodgkin's lymphoma. The sIL-2R levels of the six non-Hodgkin's lymphoma patients with stage III/IV disease were significantly higher than those of the 15 sarcoidosis patients (P < 0.001). The sIL-2R levels of the sarcoidosis patients with the panda and/or lambda sign were significantly higher than those with neither sign (P < 0.005). The sIL-2R levels of the non-Hodgkin's lymphoma patients with stage III/IV disease were significantly higher than those of the patients with stage I/II disease (P < 0.005). CONCLUSIONS: Measurement of sIL-2R levels was sometimes useful in differentiating between sarcoidosis and stage III/IV non-Hodgkin's lymphoma, staging non-Hodgkin's lymphoma, and predicting the presence of the panda and/or lambda sign in sarcoidosis patients.

Does supplementation of contrast MR imaging with thallium-201 brain SPECT improve differentiation between benign and malignant ring-like contrast-enhanced cerebral lesions?

OBJECTIVE: To determine whether thallium-201 ((201)Tl) brain single photon emission computed tomography (SPECT) could supplement magnetic resonance (MR) imaging diagnostic information by visual comparison of two separate data sets from patients with ring-like contrast-enhanced cerebral lesions. METHODS: A combination of MR imaging and (201)Tl brain SPECT sets obtained from 13 patients (10 men, 3 women) ranging in age from 26 years to 86 years (mean 61.0 years) were retrospectively reviewed. A total of 12 patients had a solitary lesion, and the others had multiple lesions. All but two intracranial foci were pathologically confirmed. The final diagnoses were six glioblastomas, two cerebral metastases from lung cancer, and one each of abscess, resolving hematoma, primary central nervous system lymphoma, toxoplasmosis, and radiation necrosis. The two separate image formats (MR images and SPECT) were shown to ten readers with practical experience. All of the MR images for each patient were shown to each reader first. After interpreting them, the readers were shown the SPECT images. Images were scored in terms of how benign or malignant the foci were on a 5-point scale from "definitely benign" to "definitely malignant." RESULTS: The improvement in the performance of all ten readers was from 67.7% to 93.8% in mean accuracy (P = 0.0028) and from 0.730 to 0.971 in mean Az value (P = 0.0069) after they were shown the (201)Tl brain SPECT images. CONCLUSIONS: (201)Tl brain SPECT should substantially increase confidence in the diagnosis of intracranial lesions with ring-like contrast enhancement when MR imaging does not permit differentiation between benign and malignant disease.

Acute Acalculous Cholecystitis Caused by Giardia lamblia.

We report a case of a 70-year-old man with acute acalculous cholecystitis caused by Giardia lamblia. Contrast-enhanced computed tomography (CT) showed distention of the gallbladder due to a pericholecystic abscess without gallstones. Magnetic resonance cholangiopancreatography and drip infusion cholecystocholangiography-CT demonstrated a stricture of the hilar bile duct and cystic duct obstruction. We conducted transpapillary bile duct brush cytology and a biopsy of the hilar bile duct stricture; numerous active trophozoites of Giardia lamblia were observed without malignant findings. We considered this bile duct lesion to be biliary giardiasis. Biliary giardiasis should be taken into consideration when diagnosing acute acalculous cholecystitis.

Pulmonary spread of laryngeal papillomatosis: radiological findings.

Laryngeal papillomatosis is a rare benign disease seen in children and young adults. The spread of laryngeal papillomas throughout the respiratory tract occurs rarely; and involvement of the distal bronchi, bronchioles, and lung parenchyma is very rare. We report a case of pulmonary spread of laryngeal papillomatosis in a 34-year-old man, focusing on the radiological evidence. Chest radiographs showed pulmonary nodules, but computed tomography scans more clearly demonstrated multiple small nodules showing cavitations and distributed centrilobularly. Pulmonary nodules and cavitations progressed gradually through the 6-year follow-up. The combination of clinical and characteristic radiological features suggests a diagnosis of pulmonary spread of laryngeal papillomatosis.