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Chronic inflammation is widely recognized as a major risk factor for cancer formation, but the underlying mechanisms are poorly understood. Recently, it was shown that Gasdermin D (GSDMD) protein drives pyroptotic cell death in macrophages upon cleavage by inflammatory caspases. Even though the Gsdmd gene is specifically expressed in the intestinal epithelium, the role of Gsdmd in the intestinal tissues remains poorly characterized. In this study, we examined the biological role of Gsdmd in colorectal cancer (CRC) development, employing an azoxymethane (AOM)/dextran sulfate sodium (DSS) carcinogenesis model. Results show that Gsdmd deficiency enhances CRC development, probably due to decreased apoptosis caused by down-regulation of interferon-gamma (IFNγ) – signal transducer and activator 1 (STAT1) signaling. Furthermore, we show that GSDMD protein is diminished in human colorectal cancer, indicating involvement of GSDMD in repression of CRC development in humans. Our findings provide a new insight into functions of Gsdmd/GSDMD in colonic inflammation and human CRC development.

The mitral L-wave, a prominent mid-diastolic filling wave in echocardiographic examinations, is associated with severe left ventricular diastolic dysfunction. The relationship between the mitral L-wave and outcome of catheter ablation (CA) in patients with atrial fibrillation (AF) has not been established. This study aimed to evaluate the predictive value of mitral L-waves on AF recurrence after CA.This was a retrospective and observational study in a single center. One hundred forty-six patients (mean age; 63.9 [56.0-72.0] years, 71.9% male) including 66 non-paroxysmal AF patients (45.2%) who received a first CA were enrolled. The mitral L-waves were defined as a distinct mid-diastolic flow velocity with a peak velocity ≥20 cm/s following the E wave in the echocardiographic examinations before CA. The patients enrolled were divided into groups with (n = 31, 21.2%) and without (n = 115, 78.8%) mitral L-waves. Univariate and multivariate analyses were carried out to determine the predictive factors of late recurrences of AF (LRAFs), which meant AF recurrence later than 3 months after the CA.During a follow-up of 28.8 (15.0-35.8) months, the ratio of LRAFs in patients with mitral L-waves was significantly higher than that in those without mitral L-waves (15 [46.9%] vs. 16 [14.0%], p .001). A multivariate analysis using a Cox proportional hazard model revealed that the mitral L-waves were a significant predictive factor of LRAFs (hazard ratio: 3.09, 95% confidence interval: 1.53-6.24, p = .002).The appearance of mitral L-waves could predict LRAFs after CA.

BACKGROUND The predictive value of the cardio-ankle vascular index (CAVI) for estimating the efficacy outcome of catheter ablation (CA) in atrial fibrillation (AF) patients is unclear. We aimed to examine the predictive performance of the CAVI for recurrences of atrial arrhythmias after CA. METHODS We enrolled a total of 193 patients with AF (paroxysmal 126 and non-paroxysmal 67) who underwent initial CA procedures at our institute, and CAVI measurements were conducted between January 2016 and March 2017. We evaluated recurrences of atrial arrhythmias after the first CA procedure as a clinical outcome. The CAVI value was assessed and the enrolled patients were divided according to the optimal CAVI value cut-off point (9.5) in the atrial arrhythmia recurrence group. RESULTS During a mean follow-up of 31.3 (17.5-43.0) months, 74 (32.5%; PaAF 41 and 49.3%; non-PaAF 33) patients had recurrences of atrial arrhythmias. The recurrence ratio of atrial arrhythmias was significantly higher in patients with a high CAVI (≥9.5) than those with a low CAVI (

Background Dealing with chemotherapy-related cardiac dysfunction (CTRCD) remains a significant problem complicated by the difficulty in early detection of cardiotoxicity. Electrocardiogram (ECG) is expected to be the most realistic methodology due to lower cost-performance and non-invasiveness. We investigated the long-term visual fluctuations in the ECG waveforms in patients with chronic doxorubicin (DOX)-induced cardiotoxicity to identify ECG indices for the early detection of cardiotoxicity. Methods We conducted a retrospective case series study by reviewing the medical records of 470 consecutive patients with malignant lymphoma who were treated with DOX at our institute between January 2010 and December 2017. Of them, 23 (4.9%) patients developed left ventricular dysfunction and were diagnosed with CTRCD using echocardiography. We assessed the ECG indices on 12-lead ECG recordings before and after treatment in 15 patients; eight patients were excluded due to conduction disturbances or atrial fibrillation. Results CTRCD was detected at a median of 475 (interquartile range, IQR: 341–1333) days after initiating chemotherapy. The evaluation of ECG indices preceding CTRCD development was performed 93 (IQR: 52–232) days before the detection of CTRCD. In the stage of CTRCD, the most significant ECG change was T-wave flattening in leads V3–V6 (12 patients, 80%). Additionally, QTa prolongation was observed in leads I and aVL (n = 10, 66%), leads II, III, and aVF (n = 9, 60%), and leads V3–V6 (n = 10, 73%). These ECG changes were not observed before the treatment but were detected mildly in the pre-CTRCD stage, which subsequently worsened in the CTRCD stage. Conclusions This study indicated that T-wave changes and QTa prolongation may be useful as an early indicator before the onset of CTRCD in patients with DOX-induced cardiotoxicity.

Malnutrition has been reported to be associated with worse clinical outcomes in various cardiovascular diseases. We aimed to investigate the clinical significance of the nutritional status in atrial fibrillation (AF) patients aged 80 years and over receiving oral anticoagulants (OACs), focusing on the difference between direct OACs (DOACs) and warfarin treatment.This was a retrospective and observational study. We enrolled 332 consecutive AF patients aged 80 years and over who were treated with OACs: DOACs (n = 256) and warfarin (n = 76). A controlling nutritional status (CONUT) score was used to evaluate the nutritional status. The enrolled patients were divided into two groups based on the CONUT score: CONUT score5 (n = 239) and CONUT score ≥5 (n = 93) groups. We investigated the relationship between the nutritional status and clinical outcomes.The CONUT score ≥5 group had significantly higher incidence of major bleeding (MB) compared to the CONUT score5 group (4.6/100 person-years vs. 0.7/100 person-years, p 0.01). On Cox hazard analysis, CONUT score ≥5 group was significantly associated with increased MB compared with the CONUT score5 group (hazard ratio: 5.80, 95% confidence interval: 1.44-23.33, p = 0.013). In the DOAC group, the incidence of MB did not differ between the CONUT score ≥5 and CONUT score5 groups (p = 0.54). In the warfarin group, MB occurred more frequently in the CONUT score ≥5 group than CONUT score5 group (p 0.01). There was no significant difference in the incidence of thromboembolic events between the CONUT score ≥5 and CONUT score5 groups in both the DOAC and warfarin groups.The prognostic values of the nutritional status based on the CONUT score for MB differed between AF patients aged 80 years and over receiving DOACs and those receiving warfarin. It may be favorable to use DOACs to avoid bleeding events in those with malnutrition.

A case of nasopharyngeal tuberculosis with cervical lymph node tuberculosis is reported. The patient was a 20-year-old female immigrant from Vietnam and cook apprentice. Her chief complaint was left neck swelling with pain for three months. She was diagnosed with left neck lymphadenitis at a previous hospital, which suspected malignant lymphoma and referred her to our hospital. At the time of the first visit, she had left lymph swelling with tenderness and granuloma-like masses in the nasopharynx. PET-CT showed accumulations in both the swollen left neck lymph and nasopharynx. The diagnosis of this case would appear to be nasopharyngeal cancer with left and neck lymph node metastasis or nasopharyngeal tuberculosis with cervical lymph node tuberculosis in addition to malignant lymphoma. Based on some examinations (biopsy, bacteria culture, and imaging), it was diagnosed as nasopharyngeal tuberculosis with cervical lymph node tuberculosis. Therefore, she was treated with anti-tuberculosis agent in respiratory medicine.

Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered.

Introduction. The canal of Nuck is an embryological remnant of the peritoneal pouch that extends into the labium majus of women. Hydrocele is the most common presentation, but only a small number of cases are reported in association with endometriosis.Case Presentation. The patient is a 45-year-old woman who presented with left inguinal mass with persistent pain. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 30 mm cystic mass, and a hydrocele of the canal of Nuck (HCN) was suspected. The excised mass was a cyst containing yellow-tan serous fluid, and the cyst wall was lined by mesothelium. The morphology was consistent with conventional HCN. However, since several foci of endometrial-like epithelium and stroma were identified beneath the mesothelium, the mass was diagnosed with HCN with endometriosis (EM-HCN).Discussion. Right-side dominance of EM-HCN is suggested by several authors, but a thorough review has never been performed. For the first time, we reviewed the literature and statistically confirmed that EM-HCNs dominantly occur on the right side compared to those without endometriosis. We consider that this supports the theory that endometriosis derives from retrograde menstruation of endometrial tissue through fallopian tubes. When endometriosis is discovered in HCN, the clinician should be aware of the possibility of pelvic endometriosis.

COVID-19 vaccine-related myocarditis has been reported worldwide. We herein report two Japanese cases with suspected vaccine-related myocarditis. A 27-year-old man was admitted with chest pain 4 days after the second vaccination. An electrocardiogram (ECG) did not reveal any significant abnormalities. The second patient, a 37-year-old man, was admitted with chest pain 9 days after the first vaccination. His ECG exhibited ST-elevation in multiple leads. In both cases, cardiac magnetic resonance imaging findings were consistent with myocarditis. They recovered with symptomatic relief within a few days. These cases suggest that the benefit of COVID-19 vaccination exceeds the risk of vaccine-related myocarditis.

The inducibility of atrial fibrillation (AF) and incidence of nonpulmonary vein (nonPV) triggers in patients with heart failure (HF) have not been elucidated. Furthermore, the relationship between AF triggers and the change in the left ventricular (LV) function after catheter ablation (CA) remains unclear.A total of 101 consecutive patients with a history of HF due to tachycardia who underwent CA of AF were prospectively enrolled (64.8 ± 10.7 years, male 72.3%, and paroxysmal AF 15.8%). According to the AF inducibility by isoproterenol (ISP), the patients were divided into two groups: inducible AF (66.3%) and noninducible AF (33.7%). Furthermore, inducible AF was categorized into a PV type (61.2%) and nonPV type (38.8%). This study investigated the AF recurrence and change in the LV ejection fraction (LVEF) after CA.AF recurred in 35 patients (34.7%) during the follow-up period (41.6 ± 26.8 months). Kaplan-Meier curves showed that patients with noninducible AF had just as bad an AF recurrence rate as those with the nonPV type. Cox proportional hazards models also revealed that noninducible AF (Hazard-ratio, 5.74; 95% CI, 1.81-18.13) was associated with a higher risk of recurrence. The LVEF significantly improved after the CA (from 49.1 ± 16.3% to 67.0 ± 7.9%). However, the nonPV type was associated with a lower improvement in the LVEF (Odds-ratio, 0.18; 95% CI, 0.05-0.70).The AF inducibility was associated with AF recurrence. Furthermore, the nonPV triggers were associated with a lesser improvement in the LVEF. Confirming the AF inducibility and triggers was important to predict the outcome after CA.

We experienced a case of anterior glottic web with bilateral vocal cord cancers. The laryngoscopic findings showed milky tumour lesions on bilateral vocal cords and a web-like formation with an adhesion in the anterior commissure. In this case, we performed laryngomicrosurgery to remove the bilateral vocal cord tumours and the anterior glottic web. This case was diagnosed as bilateral glottic carcinoma (laryngeal carcinoma TNM classification: pT1bN0M0) with an anterior glottic web. Therefore, this patient underwent radiation therapy (66 Gy). At present, one and a half years have passed since the end of radiotherapy. There is no recurrence of the glottic cancer or web. The airway at the glottis was patent. It has been reported that cutting-off the anterior glottic web could easily lead to readhesion. Accordingly, we continued to follow-up to determine whether there was a recurrence of readhesion of the anterior glottic web or glottic cancer.

A 45-year-old man suffering from dermal blistering disease with proteinuria and hematuria underwent renal biopsy. The renal biopsy specimen suggested proliferative glomerulonephritis with monoclonal IgG deposits under routine light, immunofluorescence and electron microscopy. The staining for IgG subclasses (IgG1 and IgG2) and κ/λ light chain indicated secondary immune complex type MPGN type 3. The patient had been diagnosed as having dermatitis herpetiformis (DH), a phenotype of gluten hypersensitivity prior to the appearance of the renal abnormality. Although common autoantibodies might be related to the pathogenesis of disorders in the skin and kidney, DH is mainly driven by IgA autoantibody, while MPGN is induced by IgG immune complexes. IgA was not observed in the glomeruli by immunofluorescence. Neither the examination for DH specific autoantibodies nor HLA-DQB1 genotype supported the diagnosis of DH. Reassessment of the skin biopsy record revealed that the blister was localized in the epidermis, suggesting pemphigus herpetiformis by IgG class anti-epidermal autoantibody, which also affected the renal disorder.

Intracardiac defibrillation (IDF) is performed to restore sinus rhythm (SR) during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). This study aimed to investigate the change in the IDF threshold before and after RFCA during the ablation procedure and determine whether the IDF threshold after RFCA was associated with the AF substrate and AF recurrence. A total of 141 consecutive patients with drug-refractory persistent AF (age 62.5 ± 10.3 years, 84.4% male) were enrolled in this study. Before RFCA, we initially performed IDF with an output of 1 J. When IDF failed to restore SR, the output was gradually increased to 30 J. After RFCA, we attempted pacing-induced AF to provoke other focuses of AF. When AF was induced, we performed IDF again to terminate AF with outputs of 1 to 30 J. The change in the IDF threshold to restore SR before and after RFCA was evaluated. After RFCA, the IDF threshold for restoring SR significantly decreased (from 11.5 ± 8.6 J to 4.0 ± 3.8 J, P0.001). During the follow-up (24.3 ± 12.2 months), SR was maintained in 107 patients (75.9%). The multivariate analysis using a Cox proportional-hazards model revealed that an IDF threshold of5 J after RFCA was significantly associated with the AF recurrence (HR, 3.99; 95% confidence interval 1.93-8.22; P = 0.0001). RFCA decreased the IDF threshold for restoring SR in patients with persistent AF. The IDF output of5 J after RFCA could be a predictor of AF recurrence independent of the AF substrate.

Background: Dealing with chemotherapy-related cardiac dysfunction (CTRCD) remains a significant problem complicated by the difficulty in early detection of cardiotoxicity. Electrocardiogram (ECG) is expected to be the most realistic methodology due to lower cost-performance and non-invasiveness. We investigated the long-term visual fluctuations in the ECG waveforms in patients with chronic doxorubicin (DOX)-induced cardiotoxicity to identify ECG indices for the early detection of cardiotoxicity. Methods: We conducted a retrospective case series study by reviewing the medical records of 470 consecutive patients with malignant lymphoma who were treated with DOX at our institute between January 2010 and December 2017. Of them, 23 (4.9%) patients developed left ventricular dysfunction and were diagnosed with CTRCD using echocardiography. We assessed the ECG indices on 12-lead ECG recordings before and after treatment in 15 patients; eight patients were excluded due to conduction disturbances or atrial fibrillation. Results: CTRCD was detected at a median of 475 (interquartile range, IQR: 341–1333) days after initiating chemotherapy. The evaluation of ECG indices preceding CTRCD development was performed 93 (IQR: 52–232) days before the detection of CTRCD. In the stage of CTRCD, the most significant ECG change was T-wave flattening in leads V3–V6 (12 patients, 80%). Additionally, QTa prolongation was observed in leads I and aVL (n=10, 66%), leads II, III, and aVF (n=9, 60%), and leads V3–V6 (n=10, 73%). These ECG changes were not observed before the treatment but were detected mildly in the pre-CTRCD stage, which subsequently worsened in the CTRCD stage.Conclusions: This study indicated that T-wave changes and QTa prolongation may be useful as an early indicator before the onset of CTRCD in patients with DOX-induced cardiotoxicity.

Management of hemosuccus pancreaticus (HP) due to pancreatic adenocarcinoma is problematic. This is the first report of the successful management of HP caused by pancreatic adenocarcinoma by chemoradiotherapy, which is a treatment option for cases with a high surgical risk that are not suitable for interventional radiology. In the present case, bloody pancreatic juice was detected in the main pancreatic duct, and anemia worsened without repeated blood transfusions. The patient ultimately underwent chemoradiotherapy comprising radiation of 3 Gy in 15 fractions concomitant with systemic chemotherapy of S-1. After the treatments, the anemia improved, and the patient was discharged on day 45.

In recent years, embedded real-time systems have grown in complexity and are required to be able to handle both periodic and aperiodic tasks. When an external interrupt occurs via an I/O peripheral, the program counter jumps to the corresponding exception vector. This results in large overhead due to context switching. However, embedded real-time systems are required to execute tasks in real-time with high precision. The Responsive Multithreaded Processor (RMTP), a prioritized SMT CPU, consists of eight hardware contexts treated as eight logical processing cores and has various hardware mechanisms for fine-grained real-time processing on the order of 10 µs. One hardware mechanism implemented in RMTP is an interrupt wake-up mechanism that enables interrupt-triggered thread wake ups. When a thread is designated to be an interrupt handling thread, it starts execution one clock cycle after an interrupt occurs. In this paper, we design and implement a software mechanism which reduces the interrupt response time by using this mechanism and demonstrate the effectiveness of our proposed method by RTL simulations. Evaluation results show that our proposed method achieves high real-time performance by reducing the interrupt response time by up to 82% compared to the baseline.

Introduction: In rectal cancer, distal intramural spread may sometimes occur, but a maximum extent of distal spread of > 6 cm is very rare. Case Presentation: A 65-year-old Japanese male with an advanced rectal cancer tumor with para-aortic lymph node metastasis was admitted. We performed a low anterior resection with lymphadenectomy, but the intraoperative frozen-section analysis of margins revealed malignant cell positivity; we, therefore, performed an abdominoperineal resection. Pathological findings showed that the maximum extent of distal spread was 6 cm. After 12 courses of FOLFOX4 as adjuvant chemotherapy, abdominal computed tomography revealed whole lymph node metastases, including Virchow’s node. Though FOLFIRI + panitumumab was started, he was not eligible for additional chemotherapy after 10 cycles. Conclusion: An intraoperative frozen pathology examination was helpful for the additional resection, when unexpected distal spreading had occurred in rectal cancer. The evidence of a distal negative margin should not be underestimated.

Predicting malignancy is important for adequate adjuvant therapy in patients with cancer. Due to cancer being a genetic disease, the detection of gene mutations could be helpful in predicting the prognosis and efficacy of drugs. Gastric cancer is the fifth most common cancer and is the third leading cause of cancer associated mortality worldwide. Mutations in genes may correlate with clinical information in patients with gastric cancer after surgery and, therefore, may be useful for predicting the prognosis of this disease. In the present study, to assess the usefulness of a commercial sequencing panel, TruSeq® Amplicon-Cancer Panel (Illumina), using a next-generation sequencer (Illumina MiSeq), mutation analysis of fresh as well as formalin-fixed paraffin-embedded (FFPE) gastric cancer tissues was performed retrospectively. The study group comprised of 4 patients who underwent gastrectomy for gastric cancer. Cancer and normal stomach tissues were collected immediately following surgical removal. Thereafter, the specimens were fixed in 10% neutral formalin for 24–72 h. Normal and FFPE cancer tissues were histologically examined and confirmed. A total of 3 mutations were identified in the driver genes (KRAS, TP53 and APC) in cancer tissues from 2 of the 4 patients, using fresh samples. In addition, FFPE samples were analysed for the same tissues and the same results were obtained by setting the threshold for the percentage of the mutation rate to avoid detection of pseudo-positive mutations. In conclusion, the sequencing analysis using FFPE-derived DNA samples was successfully performed.

AIM Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. METHODS A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids and tyrosine, and branched-chain amino acid-to-tyrosine ratio were determined. The hazard ratios of factors associated with liver-related events were analyzed by Cox proportional hazard analysis. RESULTS Of the 75 patients enrolled, 12 showed a decrease in serum branched-chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched-chain amino acid-to-tyrosine ratio decreased in 16 patients. During a median 5.6-year follow up, liver-related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 μmol/L was identified as a cut-off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3-101.5, P

Two unusual cases of ruptured distal posterior inferior cerebellar artery(PICA)aneurysm on the cortical segment were successfully treated with open surgery. A 76-year-old woman presented with a Hunt and Kosnik(HK)grade II Subarachnoid hemorrhage(SAH). CT showed a slight SAH in the cisterna magna and around the vermis, and fourth intraventricular hematoma. Cerebral angiography revealed an aneurysm on the cortical segment of the distal PICA. Intraoperative findings identified the aneurysm as fusiform. Trapping of the aneurysm was performed, and the indocyanine green angiography fiuding confirmed aneurysmal flow disappearance and good circulation in the cerebellar cortex. An 89-year-old woman presented with HK grade II SAH. CT revealed a thick SAH in the posterior cranial fossa, and third to fourth intraventricular hematoma with hydrocephalus. Cerebral angiography revealed an aneurysm on the cortical segment of the distal PICA. Intraoperative findings showed that the aneurysm was fusiform. Trapping and resection of the aneurysm were performed. Thirteen previous cases of aneurysms on the cortical segment of the distal PICA have been reported. Distal PICA aneurysms apparently show rebleeding more frequently than do aneurysms at other locations, so immediate direct surgery is necessary to avoid rebleeding. After proximal ligation or trapping of the aneurysm, indocyanine green angiography is useful to determine the need for revascularization.

Although primary (PGC) and remnant gastric cancers (RGC) both originate from the same gastrointestinal organ, they have very distinct clinicopathological behaviors. We hypothesized that there would be distinct differences in DNA methylation patterns that would occur during carcinogenesis of RGC and PGC, and that the differences in methylation patterns may help identify the primary factor contributing to chronic inflammation in patients with RGC. We investigated the genome-wide DNA methylation patterns of PGC and RGC tissues from 48 patients using the Infinium HumanMethylation450 Beadchip assay. The results were validated by quantitative methylation-specific PCR (qMSP) in separate, independent cohorts. We found that in our training cohort of 48 patients, the most variable genes from the gastric cancer tissues identified by the Infinium HumanMethylation450 Beadchip clustered the resultant heatmap into high and low methylation groups. On multivariate analysis, PGCs contributed significantly to the high methylation group (p = 0.004, OR 12.33), which suggested that the promoter methylation status in PGC is higher than that in RGC. Supporting this conclusion was the finding that in a separate qMSP analysis in a test cohort, the EPB41L3 gene, chosen because of its high β value on microarray analysis in the gastric cancer tissues, had significantly higher DNA promoter methylation in cancer tissues in the validation PGC tissues than in RGC. This study demonstrated that promoter methylation status in PGC is higher than in RGC. This result may reflect the effects of the absence of Helicobacter pylori on the reduced DNA methylation in the remnant stomach.

Although the specific findings of the histopathological features of the reflux esophagitis (RE) have been not vertified, many histological findings have been thought to be important in inves- tigating the RE. In this review, the histopathological findings of RE were presented according the points, described above.

Early detection and accurate diagnosis have strong impacts on cancer care; therefore, pathological diagnosis of biopsy specimen is important. It is too late that the lesion is followed up until the carcinoma invades the submucosa or more. For the better quality of life (QOL) of patients, carcinomas should be endoscopically diagnosed and resected before metastasis. To achieve correct histological diagnosis on early-stage gastric carcinomas by biopsy specimen, it is necessary to understand the difference in histological diagnosis between Japanese and Western pathologists and learn the characteristic histological features of noninvasive well-differentiated adenocarcinomas, especially those of low-grade atypia. In addition, for selecting the suitable therapy, it is also necessary to know the clinicopathological features of special types of gastric carcinomas and how to correctly perform a histological evaluation of endoscopically resected specimens.

BACKGROUND AND AIM Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection. METHODS Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method. RESULTS Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P

Aim Recent reports have indicated that aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)-infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection. Methods Expression of AKR1B10 in the liver of 119 chronic HBV-infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan–Meier analysis. Results Expression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow-up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0–38.6; P

We experienced a case of huge chronic thyroiditis with malignant lymphoma that caused dyspnea with tracheal stenosis, dysphagia with esophagus stenosis and recurrent nerve paralysis. In this case, thyroidectomy was performed and, after the surgery, there was no sign of breathing or swallowing difficulties, and it was confirmed by the postoperative computed tomography that the tracheal stenosis had improved. We considered two possible explanations for the preoperative right recurrent nerve paralysis. In the first, the right recurrent nerve could have suffered from mechanical stimulation such as compression and traction to the recurrent nerve due to enlargement of the malignant lymphoma together with chronic thyroiditis. The second possible explanation was that malignant cells had invaded neurons. We could not distinguish between the two possibilities, since this right recurrent nerve was spared and could not be examined histopathologically.

A 40-year-old man with a rare case of dissecting aneurysm of the distal middle cerebral artery(MCA, M2 segment)presented with ischemic stroke, manifesting as headache, nausea, and visual disorder. Computed tomography(CT)scan revealed cerebral infarction, and three-dimensional CT angiogram revealed stenotic change at the M2 segment. The patient was conservatively treated and remained neurologically stable. Ten months later, CT scan and magnetic resonance imaging(MRI)revealed outpouching of the M2 segment at the location of the initial stenosis. Angiogram revealed pearl and string sign at the M2 segment of the inferior trunk. The preoperative diagnosis was spontaneous dissecting aneurysm of the right distal MCA. The patient was treated with direct surgery for aneurysm resection and revascularization using the superficial temporal artery. The brain surface in contact with the dissecting aneurysm was colored xanthochromic, so minor bleeding from the dissecting aneurysm was highly suspected. Previously, 19 cases of dissecting aneurysm of the distal MCA have been reported. Distal dissecting aneurysms seem to rupture more frequently in the MCA than in the proximal segment. Long-term follow-up MRI and angiogram might be important, not only in the acute stage in patients with atypical caliber changes in the distal MCA. Immediate direct surgery is indicated to avoid hemorrhagic stroke if dilatation of the major trunk at the dissection is suspected.

A 69-year-old man was under maintenance dialysis due to diabetic renal failure. He had a drop in blood pressure during dialysis, developed hematemesis, and was transported to our hospital. Emergency upper gastrointestinal endoscopy revealed diffuse erosion, mucosal sloughing, and edematous mucosa in the upper body of the stomach to the posterior wall of the antrum and to the greater curvature, which were considered to be an ischemic change. His underlying diseases included diabetic renal failure, chronic arteriosclerosis obliterans, cerebral infarction, internal carotid artery stenosis, hypertension, and myocardial infarction. Blood evaluation showed only mild inflammation and no fibrinolytic hyperactivity. Contrast-enhanced computed tomography (CECT) showed no occlusion of blood vessels. It was considered that the patient had a transient ischemic change due to blood pressure drop. The patient's condition improved with conservative treatment.

Laryngeal polyps are common, but some hospitals have reported that a giant vocal fold polyp could cause dyspnea. We encountered a giant vocal fold polyp with dyspnea. Under general anesthesia, laryngomicrosurgery successfully improved the symptoms of the dyspnea. In this case, stenosis of the posterior glottis (considered to be the respiratory glottis) due to a giant vocal fold polyp was thought to be the cause of the preoperative dyspnea.

Background. Despite complete resection of gastrointestinal stromal tumors (GIST), recurrent and/or metastatic disease occurs, often depending on the grade of malignancy. As such, markers are needed that accurately predict patients at high risk for recurrence. Previously our group reported Pfetin as a prognostic biomarker for GIST. In order to create an approach for predicting risk of recurrence, we incorporated Pfetin expression with clinicopathological data to produce a predictive model.Object. Forty-five patients with localized primary GIST were treated with complete gross surgical resection surgically at our institution between 1995 and 2010 were included. The majority of tumors originated in the stomach (38 cases), as well as small intestine (6 cases) and rectum (1 case).Method. (1) We performed retrospective analysis of the connection between Pfetin expression, clinicopathological data, and incidences of recurrence, using bivariate and multivariate analyses. (2) The reactivity of the monoclonal antibody against Pfetin was examined by immunohistochemistry.Pfetin. We have reported Pfetin, identified microarray technology, and compared between statistically different GISTs for good and poor prognoses and for prognostic marker.Results. There were 7 cases of recurrences. (1) By univariate analysis, tumor size, mitoses, exposure to abdominal cavity, and complete tumor removal predicted risk of recurrence. (2) Pfetin-negative cases were significantly related to recurrence (P= 0.002).Conclusions. This analysis demonstrates that lack of Pfetin expression is an additional predictor of recurrence in resected GIST. Further study may determine the role of this variable added to the current predictive model for selection of adjuvant therapy.

Purpose: Submucosal invasive colorectal carcinoma (SICC) exhibits lymph node metastasis in about 10% of patients. Therefore, endoscopic resection is insufficient for cases of SICC at risk of lymph node metastasis, and surgical resection accompanied with lymph node dissection is necessary. However, because additional intestinal resection is unnecessary for cases without lymph node metastasis, more rigid criteria are required in order to decrease the incidence of unnecessary further intestinal resection. We retrospectively identified predictive factors for lymph node metastasis in submucosal invasive colorectal carcinoma. Methods: One hundred and two patients who underwent intestinal resection as the first treatment or additional intestinal resection after endoscopic resection at our department between 1999 and 2012 were enrolled in the present study. Clinicopathological factors were analyzed to determine predictive factors related to lymph node metastasis. Results: The multivariate analysis revealing only depth of submucosal invasion (≤2700 μm) was found to be a significant, independent predictive factor of lymph node metastasis (P = 0.04, Odds ratio: 4.18, 95% CI: 1.06 - 16.40). Conclusion: It is considered that the refinement of the criteria in the present study will be very useful, especially in the patients for whom careful judgment is required when considering additional intestinal resection.

Purpose: Although primary gastric cancers (PGC) and remnant gastric cancers (RGC) both originate from the same gastrointestinal organ, they have very distinct clinicopathological behaviors. Due to the importance of chronic inflammation in the carcinogenesis of gastric malignancies, we hypothesized that DNA promoter hypermethylation would play a critical role in the carcinogenesis of RGC as well as PGC. Methods: We investigated the genome-wide DNA methylation patterns of PGC and RGC tissues from 48 patients from an academic medical center in Japan using the Infinium HumanMethylation450 BeadChip assay. The results were validated by quantitative methylation-specific PCR (qMSP) in separate, independent cohorts. Results: We found that in our training cohort of 48 patients, genes from the gastric cancer tissues identified by the Infinium HumanMethylation 450 Beadchip clustered into high and low methylation groups on multivariate analysis (p=0.004, OR=12.33). PGCs contributed significantly to the high methylation group suggesting that the DNA promoter methylation status in PGC is higher than that in RGC. Supporting this conclusion was the finding that in a separate qMSP analysis in a test cohort, the gene A had significantly higher DNA promoter methylation in cancer tissues in the validation PGC tissues than in RGC. Conclusion: This study demonstrated that DNA promoter methylation status in PGC is higher than in RGC. This result may reflect the effects of Helicobacter pylori on the induction of DNA methylation in the remnant stomach. Citation Format: Tomoaki Ito, Kiichi Sugimoto, Hajime Orita, Masahiro Maeda, Hiroshi Moro, Toshikazu Ushijima, Hitoshi Katai, Ryo Wada, Kazuhiro Sakamoto, Koichi Sato, Malcolm V. Brock. DNA methylation genome-wide analysis in remnant gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 819.

Background and Aim The purpose of this study was to evaluate the usefulness of liver stiffness measurement (LSM) for assessing the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients receiving interferon (IFN) therapy. Methods One hundred fifty-one CHC patients who underwent LSM and received IFN therapy were included in the estimation cohort, and 56 were included in the validation study. The cumulative HCC incidences were evaluated using Kaplan–Meier plot analysis and the log-rank test. Multivariate Cox proportional hazard analyses were used to estimate the hazard ratios (HRs) of variables for HCC. Results In the estimation cohort, 9 of 151 patients developed HCC during the median follow-up time of 722 days. Multivariate analysis identified three independent risk factors for HCC: LSM (≥ 14.0 kPa, HR 5.58, P = 0.020), platelet count (

We previously reported a relationship between depth of submucosal invasion of early colorectal carcinomas and desmoplastic reaction (DR). However, poor inter-observer agreement on the histopathological diagnosis of DR in biopsy specimens with hematoxylin and eosin (H&E) staining has been the major critique of this tool. In this study, reproducibility of the histopathological diagnosis of DR was evaluated. Furthermore, we investigated the possible improvement of the reproducibility after education about histological characteristics and tried to identify histological characteristics that are most important in the recognition of DR. A total of 34 H&E stained slides were included in this study and analyzed by three pathologists. Slides were reviewed before and after education about histological characteristics of DR. Kappa statistics were used to compare the inter-observer variability. We investigated the relationship between DR and histopathological factor. The inter-observer agreement during the first session varied between 0.30 and 0.63, which improved during the second session toward an agreement between 0.58 and 0.71. Myofibroblast proliferation associated with cancer invasion was found to be the most useful in the diagnosis of DR. In conclusion, the correct detection of myofibroblasts may facilitate the standardization of diagnosis of DR.

Two cases of mucinous cystadenoma of the appendix successfully treated by laparoscopy are reported. An 81-year-old woman with lower right back pain was diagnosed with mucinous cystadenoma of the appendix or appendiceal carcinoma and underwent elective laparoscopic surgery. The other case involved a 70-year-old man with hematochezia who was diagnosed with mucinous cystadenoma. He also underwent elective laparoscopic surgery. In these two cases, gauze was folded around the tumors rather than grasping them directly. The postoperative courses were uneventful, and these patients had no recurrent disease at 2-year follow-up. In such cases, surgical excision of the tumor without rupture is of paramount importance because rupture of the lesion can cause pseudomyxoma peritonei. Though appendiceal mucinous cystadenoma has been considered a contraindication of laparoscopic resection, it was possible to achieve this by using a laparoscopic procedure with a gauze technique.

OBJECTIVE Genotype 1 chronic hepatitis C (G1CHC) is generally accompanied by metabolic disturbances related to visceral obesity, such as insulin resistance, steatosis, or dyslipidemia. Because these abnormalities negatively influence the clinical course of G1CHC, we sought to clarify the effect of visceral obesity on the pathophysiology of G1CHC. METHODS We evaluated 180G1CHC patients for the presence of visceral obesity on the basis of computed tomography findings. Multivariate analysis was performed to estimate the relationship between visceral obesity and demographic, viral, and biochemical characteristics of patients. The associations of visceral obesity with histological findings and serum adipokine levels were also analyzed. RESULTS Multiple logistic regression analysis revealed that visceral obesity was independently associated with metabolic syndrome, platelet count, high-density lipoprotein level, and serum viral load in elderly patients (≥65 years). Multiple linear regression analysis confirmed the association between visceral obesity and high viral load. However, visceral obesity was not correlated with viral load in non-elderly patients (

Although both lung cancer and pulmonary tuberculosis (TB) commonly occur in clinical practice, little attention has been paid to their coexistence. A 62‐year‐old female was admitted with acute dyspnoea secondary to cardiac tamponade. During her admission, a mass lesion harbouring air bronchograms in the right upper lobe rapidly increased in size. Surgical lung, pericardial, and pleural specimens yielded TB from a nodule in the right upper lobe and lung adenocarcinoma from the pericardium and pleura. Anti‐tuberculous therapy was administered and gefitinib was subsequently started after the positive identification of epidermal growth factor receptor (EGFR) mutation (exon 19 deletion). The patient's general condition gradually improved with the anti‐tuberculous and the EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) treatment. Dual pathology is important to consider in patients with atypical radiological appearances. In those with proven EGFR mutation positive for lung cancer and pulmonary TB, sequential anti‐tuberculous medication followed by EGFR‐TKI treatment is advised.