[A case of extensive digestive tract metastasis from invasive lobular carcinoma of the breast].

A 59-year-old female patient underwent surgery for invasive lobular carcinoma of the right breast 12 years ago. The final diagnosis was invasive lobular carcinoma (T4N1M0 stage IIIB). She underwent chemotherapy, radiotherapy, and hormonal therapy after surgery. She had abdominal bloating and vomiting 12 years after surgery. Contrast-enhanced computed tomography (CECT) and esophagogastroduodenoscopy showed edematous thickening from the stomach to the duodenum and moderate amounts of ascites. Lymph node metastasis was not observed. Biopsy specimens of the stomach revealed signet ring cell carcinoma. Immunochemical studies (ER, GCDFP-15, MUC1, MUC5AC, and MUC6) confirmed gastroduodenal metastasis of invasive lobular carcinoma. Ascites disappeared after she underwent chemotherapy with paclitaxel and bevacizumab; however, wall thickening had spread from the lower esophagus to the stomach, small intestine, colon, and rectum on the CECT. She died 7 months after the diagnosis of gastroduodenal metastasis. Herein, we report a case of invasive lobular carcinoma of the breast with extensive digestive tract metastasis.

Gastrointestinal adverse reactions reduce the success rate of Helicobacter pylori eradication therapy: A multicenter prospective cohort study.

BACKGROUND: The screening and treatment of Helicobacter pylori infection for all junior high students in Saga Prefecture, Japan, were started in 2016. The present study aims to evaluate the influence of adverse reactions on the success of the eradication therapy. METHODS: From 2017 to 2019, 25,006 third-grade junior high school students were tested for urinary anti-H. pylori antibodies. Positive cases were confirmed by H. pylori stool antigen tests. Of the 531 students who were found to be H. pylori-positive, 390 (358 in first-line and 32 in second-line therapy) underwent eradication therapy, and 274 (242 in first-line and 32 in second-line) students actually completed a self-reported form to rate stool consistency (based on the Bristol Stool Scale), the maximum number of bowel movements, and abdominal symptoms during the 7 days of treatment. RESULTS: Among the 274 students, the total of primary and secondary eradication success rates was 87% (95% confidential interval: 82.9-90.1) in intention-to-treat analysis. On days 4, 5, and 6, stool consistency was looser in the primary eradication failure group than in the success group (p < .05). Looser stool consistencies were observed in male students with abdominal pain compared to those who did not experience pain (p < .05). Abdominal pain and diarrhea were detected in 28.5% and 42.7% of the subjects, respectively. The overall incidence of other adverse events was low (n = 8/274, 2.9%), and only two students discontinued treatment because of adverse events. CONCLUSIONS: Softening of the stool was related to the eradication failure in the junior high school students, especially in males with abdominal pain. Adverse effects did not induce discontinuation of the eradication treatment.

Development of a Novel Algorithm to Detect Atrial Fibrillation Using an Automated Blood Pressure Monitor With an Irregular Heartbeat Detector.

BACKGROUND: Atrial fibrillation (AF), which contributes to an increased risk of stroke, frequently remains undetected, suggesting an unmet need for easier and more reliable AF screening. The reports on screening AF using an Omron blood pressure (BP) monitor with an irregular heartbeat (IHB) detector show inconsistent results, so the aim of this study was to develop a novel algorithm to accurately diagnose AF with 3 BP measurements using an Omron automated BP monitor with IHB detector.Methods and Results:In total, 303 general cardiac patients were included. Real-time single-lead ECG revealed AF in 44 patients. BP measurement was performed 3 times per patient using the Omron BP monitor HEM-907, and the number of IHBs detected was recorded. Based on these data, we developed the following algorithm: ≥1 IHB is detected during at least 2 of 3 BP measurements and the maximum number of IHBs detected is ≥2. Using this algorithm, we achieved a sensitivity of 95.5% and specificity of 96.5%, for diagnosing AF. CONCLUSIONS: The novel algorithm with 3 BP measurements using the Omron automated BP monitor with IHB detector showed high sensitivity and specificity for diagnosing AF in general cardiac patients.

Prospective, randomized, controlled study of the efficacy of transcatheter arterial chemoembolization with miriplatin for hepatocellular carcinoma.

AIM: Transcatheter arterial chemoembolization (TACE) has been recognized as a treatment option for patients with intermediate hepatocellular carcinoma (HCC). This randomized, controlled study compared the local control efficacy of TACE with miriplatin (platinum monohydrate) or with epirubicin. METHODS: The study group consisted of 200 Japanese patients with unresectable HCC treated at the Kitasato University East Hospital (Sagamihara, Japan) between July 2010 and June 2013. The primary end-point of the study was time to tumor progression (TTP). RESULTS: We analyzed 198 patients (99 in the miriplatin group and 99 in the epirubicin group) treated with TACE. The median TTP in the epirubicin group was 5.9 months (95% confidence interval [CI], 4.8-7.0) and 7.6 months (95% CI, 5.8-9.4) in the miriplatin group. There was a significant difference between the two groups (P = 0.021; risk ratio, 1.488; 95% CI: 1.061-2.086). In the epirubicin group, 53 patients (53%) had complete response, 24 patients (24%) had partial response, 12 patients (12%) had stable disease, and 10 patients (10%) had progressive disease. In the miriplatin group, 38 patients (38%) had complete response, 41 patients (41%) had partial response, 2 patients (2%) had stable disease, and 18 patients (18%) had progressive disease. There was no significant difference in the response rate (P = 0.862). Overall incidences of adverse events and adverse drug reactions did not differ significantly between the two groups. CONCLUSION: Miriplatin proved more effective than epirubicin in TACE for unresectable HCC. The trial described in this work has been registered under the trial number: UMIN000004790.

Correction of collimator-dependent differences in the heart-to-mediastinum ratio in 123I-metaiodobenzylguanidine cardiac sympathetic imaging: Determination of conversion equations using point-source imaging.

BACKGROUND: Septal penetration causes collimator-dependent differences in the heart-to-mediastinum (H/M) ratio in 123I-metaiodobenzylguanidine (MIBG) cardiac imaging. We investigated generally applicable methods to correct such differences. METHODS AND RESULTS: Four hours after 123I-MIBG injection, 40 patients underwent anterior chest imaging successively with medium-energy (ME) and various non-ME collimators. The H/M ratios obtained with the non-ME collimators before and after 123I-dual-window penetration correction were compared with the ME-derived standard values to determine patient-based conversion equations for empiric and combined corrections, respectively. A 123I point source was imaged with various collimators, and the central ratio, the ratio of count in a small central region of interest to count in a large one, was calculated. The method of predicting the conversion equations from the central ratios was determined. Correction using the patient-based conversion equations removed systematic underestimation of the H/M ratios obtained with the non-ME collimators, and combined correction depressed residual random errors to some degree. Point-source-based equations yielded results comparable to the patient-based equations. CONCLUSIONS: Empiric and combined corrections effectively reduce collimator-dependent differences in the H/M ratio. The conversion equations can be predicted from simple point-source imaging, which would allow to apply these corrections to data obtained with various collimators.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging is useful in predicting malignant potential of vascular transformation of hypointense hypovascular nodules on gadoxetic acid-enhanced magnetic resonance imaging.

AIM: To examine whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) can be used to assess the malignant potential of hepatic hypovascular nodules showing hypointensity during the hepatobiliary phase (HBP) on gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI. METHODS: The study included 42 patients with chronic liver disease who had small hypovascular nodules (5-15 mm) showing hypointensity during the HBP on Gd-EOB-DTPA-enhanced MRI. The SPIO-enhanced T2-weighted MRI analyzed whether the signal intensity of each nodule was high. Nodules were prospectively followed up until hypervascularization by periodic Gd-EOB-DTPA-enhanced MRI. Initial MRI findings and clinical variables were used to analyze predictive factors for hypervascularization. RESULTS: We analyzed 77 nodules, of which 19 (25%) showed hypervascularization during the observation period. The cumulative rates for hypervascularization were 11% and 22% at 1 and 2 years, respectively. Hyperintensity was observed in 12 nodules (16%) on SPIO-enhanced T2-weighted MRI; among these, 7 (58%) showed hypervascularization, whereas 12 (18%) of the remaining 65 nodules without hyperintensity showed hypervascularization (P = 0.007). A Cox model revealed that independent predictors of hypervascularization included hyperintense nodules on SPIO-enhanced MRI (P < 0.001). The cumulative rates for hypervascularization in hyperintense nodules on SPIO-enhanced MRI were 52% at 1 year, whereas these rates were 3% for non-hyperintense nodules. CONCLUSION: Superparamagnetic iron oxide-enhanced MRI is useful for predicting the malignant potential of vascular transformation of hypovascular nodules with hypointensity observed in the HBP on Gd-EOB-DTPA-enhanced MRI.

Two-Dimensional Spoiled Gradient-Recalled Echo Magnetic Resonance Imaging of the Liver Using Respiratory Navigator-Gating Techniques.

OBJECTIVE: We assessed the feasibility of T1-weighted 2-dimensional spoiled gradient-recalled (2D SPGR) acquisition in steady-state imaging of the liver with various respiratory navigator gating techniques. METHODS: A total of 12 healthy volunteers underwent in-phase and out-of-phase 2D SPGR imaging of the liver during breath-holding and free-breathing. Four techniques for respiratory navigation, 2 conventional navigator techniques and 2 self-navigator techniques, were used for free-breathing imaging. RESULTS: Good navigator waveforms were obtained in conventional navigation, whereas fluctuations were evident in self navigation. All of the 4 navigator-based methods provided better images in terms of background signals and visual image quality compared with images obtained with no respiratory control. However, differences remained in comparison with breath-holding. Superiority of self-navigation to conventional navigation was not shown. CONCLUSIONS: Navigator-gating techniques improved 2D SPGR images of the liver acquired during free-breathing, suggesting feasibility and beneficial effects, although navigator-based images were still inferior to breath-hold images.

Three-dimensional computed tomography of portopulmonary venous anastomoses in patients with esophageal varices before treatment.

AIM: Portopulmonary venous anastomoses (PPVA) are shunts between esophageal varices and pulmonary veins. Because PPVA can cause serious complications at the time of sclerotherapy for esophageal varices, it is essential to confirm the existence of any PPVA before treatment. METHODS: The study group comprised 101 patients in whom hemodynamics were evaluated on three-dimensional computed tomography (3D-CT) before either elective or prophylactic treatment of esophageal varices at Kitasato University East Hospital from October 2007 through August 2013. The presence or absence of PPVA, laboratory test results and 3D-CT findings were retrospectively examined in these patients. RESULTS: Nine patients had PPVA, and 92 patients did not. The underlying diseases in the PPVA group were: hepatitis C liver cirrhosis in three; non-B, non-C liver cirrhosis in three; non-alcoholic steatohepatitis in one; primary biliary cirrhosis in one; and autoimmune hepatitis in one. The distribution of underlying diseases did not differ between the PPVA group and the non-PPVA group. When the study variables were statistically compared between the groups, the incidence of large, coil-shaped esophageal varices (grade F3) differed significantly between the groups (P = 0.001). Multivariate analyses of factors related to PPVA revealed that only the grade F3 type of esophageal varices differed significantly between the groups (P = 0.005; hazard ratio, 5.21; 95% confidence interval, 3.1-16.4). CONCLUSION: In patients with grade F3 esophageal varices, the treatment method should be selected on the basis of an accurate hemodynamic analysis using 3D-CT before therapy.

Higher Frequency of Reflux Symptoms and Acid-Related Dyspepsia in Women than Men Regardless of Endoscopic Esophagitis: Analysis of 3,505 Japanese Subjects Undergoing Medical Health Checkups.

BACKGROUND/AIMS: This study aimed at (i) clarifying the factors associated with high scores on the modified frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) among 3,505 relatively healthy subjects undergoing routine medical health checkups with gastrointestinal endoscopy and (ii) comparing risk factors for high FSSG scores between subjects with and without reflux esophagitis. METHODS: In total, 3,505 subjects (male/female: 1,922/1,583) who underwent upper gastrointestinal endoscopy during health medical checkups at 5 hospitals in Saga, Japan from January 2013 to December 2013 were enrolled. All subjects completed a modified FSSG questionnaire, which comprised 7 questions regarding reflux symptoms and 7 questions regarding acid-related dyspepsia. Each question was assigned a score based on the frequency of symptoms. RESULTS: Younger age, female gender, hiatal herniation, and endoscopic reflux esophagitis were risk factors for a FSSG score with a high total. Subjects with high scores but without esophagitis were women, and hiatal herniation and Barrett's esophagus were frequently seen in patients with reflux esophagitis. CONCLUSION: Younger age, female gender, hiatal hernia, and endoscopic esophagitis were risk factors for a high FSSG score, and women tended to complain of upper gastrointestinal symptoms more frequently than did men among subjects without endoscopic esophagitis.

A preliminary study on pre-operative tumor volumetry measured by three-dimensional computer tomography in gastric cancer.

BACKGROUND/AIMS: The aim of the present study was to evaluate the clinical significance of tumor volumetry measured by three-dimensional (3-D) multidetector row computed tomography (MD-CT). METHODOLOGY: A total of 50 patients with gastric cancer who had undergone pre-operative tumor volumetry using 3D-MD-CT followed by subsequent laparotomy (11 women, 39 men; mean age 63.9 years) were examined. Tumor volume and conventional clinicopathological factors were studied and then analyzed with respect to survival. RESULTS: Tumor volume was distributed widely and ranged from 0.16 cm3 to 363.5 cm3 with a mean of 43.6 cm3 (<10 cm3, 21 tumors; ≥10 cm3, 29 tu- mors). Significant differences in survival were found for volume (<10.0 cm3 vs. ≥10.0 cm3; p=0.0414), and depth of invasion (T1-2 vs. T3-4; p=0.0475), but not for diameter (<50 mm vs. ≥50 mm; p=0.2142), location (proximal third vs. middle or distal third; p=0.3254), macroscopic type (localized vs. invasive; p=0.3619), or microscopic type (differentiated vs. undifferentiated; p=0.1230). CONCLUSIONS: The present findings suggest that tumor volume measured by pre-operative 3D-MD-CT offers an alternative indicator for determining the prognosis in gastric cancer.

Benefits and problems of transarterial therapy in patients with hepatocellular carcinoma and chronic kidney disease.

PURPOSE: To evaluate the feasibility of transarterial therapy (transcatheter arterial chemoembolization and transcatheter arterial infusion) for patients with hepatocellular carcinoma and chronic kidney disease (CKD). MATERIALS AND METHODS: The study enrolled 35 patients who received transarterial therapy. The patients were classified into a CKD group (n = 10 nondialysis chronic kidney disease [NDCKD] and n = 9 end-stage renal disease [ESRD]) or a non-CKD group (n = 16). The survival rates between the two groups were compared using two different starting points: (a) from initial diagnosis of hepatocellular carcinoma and (b) from enrollment in the study. The tolerance of transarterial therapy in patients with CKD was evaluated by comparing the incidence of major adverse events. RESULTS: The 2-year and 5-year survival rates from initial diagnosis were 83.9% and 53.8% in the CKD group and 70.1% and 40.4% in the non-CKD group (P = .478). The corresponding 3-year survival rate from enrollment in the two groups was 25.6% and 41.2%, respectively (P = .995). The 2-year and 5-year survival rates from initial diagnosis were 70.1% and 40.4% in the non-CKD group, 90.0% and 39.4% in NDCKD patients, and 76.2% and 76.2% in ESRD patients (P = .380). The corresponding 2-year survival rates from enrollment in these groups were 54.9%, 48.0%, and 48.6% (P = .943). Severe contrast-induced nephropathy (n = 3) and late-onset death caused by cholesterol crystal embolism (n = 1) were observed in the NDCKD group. CONCLUSIONS: Transcatheter arterial chemoembolization is feasible in patients with CKD by instituting periprocedural hemodialysis with similar 2-year and 5-year survival compared with patients without CKD.

An improved method for estimating the heart-to-mediastinum ratio from cardiac sympathetic nerve imaging with low-energy high-resolution collimators.

BACKGROUND: Septal penetration causes underestimation of the heart-to-mediastinum (H/M) ratio in cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging with a low-energy high-resolution (LEHR) collimator. We aimed to improve the method of estimating the H/M ratios using the LEHR collimator. METHODS AND RESULTS: 4 hours after (123)I-MIBG injection, 40 patients were imaged successively with the medium-energy (ME) and LEHR collimators using gamma cameras having 3/8-inch crystals. Severe underestimation of the H/M ratios was observed with the LEHR collimator when compared to the ME collimator. Narrowing the energy window width did not reduce the underestimation. Application of (123)I-dual-window (IDW) correction using a narrow or wide subwindow reduced the underestimation substantially but not entirely. The H/M ratios estimated from the LEHR images with or without IDW correction were corrected based on their correlations with the ratios estimated from the ME images. This empiric correction removed systematic underestimation, and residual errors were reduced when the H/M ratios after IDW correction were converted using the empiric equation. The conversion equation was successfully applied to the correction of the H/M ratios determined in another 40 patients using a 5/8-inch crystal. CONCLUSIONS: In estimating the H/M ratios using an LEHR collimator, empiric correction combined with IDW correction improves concordance with ME-based values in comparison with empiric correction alone.

99mTc-Sn-colloid SPECT/CT in thoracic splenosis after esophageal cancer surgery.

Splenosis occurs as a result of autotransplantation of splenic tissue following splenic injury or splenectomy. A 56-year-old man with esophageal cancer underwent thoracoscopic-assisted subtotal esophagectomy accompanied by three-field lymph node dissection, and retrosternal gastric tube reconstruction. The spleen was injured during the surgery and was removed. A retrosternal nodule of 12 mm in diameter was detected near the reconstructed gastric tube on computed tomography (CT) performed 3 years and 6 months postoperatively. Retrospectively, the nodule was observed in the same area on early postoperative CT and gradually increased in size. No accessory spleen was identified on the preoperative CT. Splenosis was suspected, and 99mTc-Sn-colloid single photon emission computed tomography (SPECT)/CT was performed. It revealed intense uptake in the retrosternal nodule, consistent with the diagnosis of thoracic splenosis. Subsequently, the patient has been under observation without treatment. 99mTc-labeled colloid SPECT/CT allowed confident diagnosis of thoracic splenosis following esophageal cancer surgery. This examination is considered valuable for the evaluation of ectopic splenic tissue.

The impact of dietary fat type on lipid profiles in lean mass hyper-responder phenotype.

Key Clinical Message: Although the lean mass hyper-responder (LMHR) phenotype is well known, its diagnosis is impeded by the influence of fat type and intake on the lipid profile. Accordingly, a detailed assessment is warranted if LMHR is suspected. Abstract: A 47-year-old man with suspected familial hypercholesterolemia presented with elevated triglyceride and low-density lipoprotein cholesterol levels. He had adhered to a ketogenic diet and was suspected of a lean mass hyper-responder phenotype; however, his lipid profile did not meet the definition. His lipid profile improved through dietary management without medication.

Phenotypic homozygous familial hypercholesterolemia successfully treated with proprotein convertase subtilisin/kexin type 9 inhibitors.

Recent data reveal phenotypic HoFH patients may be responsive to PCSK9 inhibitors, challenging prior assumptions. Genetic testing advancements now more accurately forecast patient responses to these therapies, improving treatment strategies.

Transitional Medicine of Intractable Primary Dyslipidemias in Japan.

Transitional medicine refers to the seamless continuity of medical care for patients with childhood-onset diseases as they grow into adulthood. The transition of care must be seamless in medical treatment as the patients grow and in other medical aids such as subsidies for medical expenses in the health care system. Inappropriate transitional care, either medical or social, directly causes poorer prognosis for many early-onset diseases, including primary dyslipidemia caused by genetic abnormalities. Many primary dyslipidemias are designated as intractable diseases in the Japanese health care system for specific medical aids, as having no curative treatment and requiring enormous treatment costs for lipid management and prevention of complications. However, there are problems in transitional medicine for primary dyslipidemia in Japan. As for the medical treatment system, the diagnosis rate remains low due to the shortage of specialists, their insufficient link with generalists and other field specialists, and poor linkage between pediatricians and physicians for adults. In the medical care system, there is a mismatch of diagnostic criteria of primary dyslipidemias between children and adults for medical care expense subsidization, as between The Program for the Specific Pediatric Chronic Diseases and the Program for Designated Adult Intractable Diseases. This could lead some patients subsidized in their childhood to no longer be under the coverage of the aids after transition. This review intends to describe these issues in transitional medicine of primary dyslipidemia in Japan as a part of the efforts to resolve the problems by the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare of Japan.

Improved Efficiency of the Clinical Diagnostic Criteria for Familial Hypercholesterolemia in Children: A Comparison of the Japan Atherosclerosis Society Guidelines of 2017 and 2022.

AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which increases the risk of premature coronary artery disease. Early detection and treatment are vital, especially in children. To improve FH diagnosis in children, the Japan Atherosclerosis Society (JAS) released new guidelines in July 2022. This study assessed and compared the sensitivity and specificity of the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. METHODS: From September 2020 to March 2023, 69 children with elevated plasma LDL-C levels (≥ 140 mg/dL) were included in a pediatric FH screening project in Kagawa. The children were evaluated using genetic testing alongside the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. RESULTS: Using the JAS pediatric FH 2017 criteria, eight children were diagnosed as FH-positive and 61 children as FH-negative. The JAS pediatric FH 2022 criteria identified 15 children with definite FH, 31 with probable FH, and 23 with possible FH. Genetic testing detected FH pathogenic variants in 24 children. The sensitivity and specificity for the JAS pediatric FH 2017 criteria were 0.292 and 0.978, respectively. For the JAS pediatric FH 2022 criteria, the sensitivity was 0.542 for definite FH with a specificity of 0.956, and 0.917 for probable FH with a specificity of 0.467. CONCLUSION: The clinical diagnostic criteria of the JAS pediatric FH 2022 guidelines demonstrated improved diagnostic efficiency compared with those of 2017, as evidenced by the increased sensitivity while preserving specificity.

Motion artifact reduction of diffusion-weighted MRI of the liver: use of velocity-compensated diffusion gradients combined with tetrahedral gradients.

PURPOSE: To assess the effect of motion artifact reduction on the diffusion-weighted magnetic resonance imaging (DWI-MRI) of the liver, we compared velocity-compensated DWI (VC-DWI) and VC-DWI combined with tetrahedral gradients (t-VC-DWI) to conventional DWI (c-DWI) in the assessment of apparent diffusion coefficients (ADCs) of the liver. MATERIALS AND METHODS: In 12 healthy volunteers, the liver was scanned with c-DWI, VC-DWI, and t-VC-DWI sequences. The signal-to-noise ratio (SNR) and ADC of the liver parenchyma were measured and compared among sequences. RESULTS: The image quality was visually better for t-VC-DWI than for the others. The SNR for t-VC-DWI was significantly higher than that for VC-DWI (P < 0.05) and comparable to that for c-DWI. ADCs in both hepatic lobes were significantly lower for t-VC-DWI than for c-DWI (P < 0.01). ADC in the left lobe was significantly lower for VC-DWI than for c-DWI (P < 0.01). Although ADC in the left lobe was significantly higher for c-DWI (P < 0.01), no significant differences in ADCs were found between the right and left lobes for VC-DWI and t-VC-DWI. CONCLUSION: The use of a t-VC-DWI sequence enables us to correct ADCs of the liver for artificial elevation due to cardiac motion, with preserved SNR.