The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients.

BACKGROUND: There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients. METHODS: Postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed. RESULTS: Among 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05). CONCLUSIONS: PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.

[Perioperative Outcome of Laparoscopic Surgery after Colonic Stent Placement for Obstructive Colorectal Cancer].

In recent years, bridge to surgery(BTS), in which surgery is performed after colorectal stenting for obstructive colorectal cancer, has gradually become popular, and laparoscopic surgery is also a treatment option. From January 2020 to December 2022, we retrospectively evaluated clinicopathological factors in 18 colorectal cancer cases who underwent radical resection after colorectal stenting. We found no difference in patient background, histopathological factors, primary anastomosis rate, stoma creation rate, operative time, postoperative complication rate and length of hospital stay between the laparoscopic surgery(L)and open surgery(O)groups. Blood loss was significantly lower in group L. In T4 patients, laparoscopic surgery after colorectal stenting can be safely performed, but conversion to open surgery may be necessary. Surgery after colorectal stenting should be performed based on preoperative accurate imaging and sufficient experience.

[A Case of Sigmoid Colon Cancer with Retroperitoneal Fibrosis Using Intraoperative Indocyanine Green Fluorescence Angiography for Colorectal Anastomosis].

A 72-year-old man was presented with anemia and diagnosed with sigmoid colon cancer by colonoscopy. CT showed a soft tissue density around the retroperitoneum, leading to the diagnosis of retroperitoneal fibrosis. Stenosis of left ureter, inferior mesenteric artery, and left colic artery due to the soft tissues were detected. Sigmoidectomy and retroperitoneal biopsy were performed, and colorectal anastomosis was completed after confirming the intestinal blood flow by ICG fluorescence angiography. In retroperitoneal fibrosis, identifying blood vessels intraoperatively can be difficult. ICG fluorescence angiography is useful for reliable anastomosis in colorectal cancer surgery with retroperitoneal fibrosis.

Quality and quantity of visceral fat tissue are associated with insulin resistance and survival outcomes after chemotherapy in patients with breast cancer.

PURPOSE: Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play significant roles in adipocyte function, and are related to insulin resistance. We tested the hypothesis that high amounts of upper VAT (aVAT) and low-quality VAT worsen treatment outcomes via altered insulin metabolism. METHODS: Cohort 1 included 106 women with breast cancer who were undergoing surgery. Homeostasis model assessment of insulin resistance (HOMA-R), insulin-like growth factor (IGF)-1, and IGF-binding protein 3 (IGFBP3) were measured before the initiation of treatment. aVAT was measured via computed tomography (CT). VAT quality was assessed using CT-determined Hounsfield units (VAT-HU). Associations between the variables investigated and VAT quality and quantity were analyzed. Cohort 2 included 271 patients who underwent chemotherapy. Associations between the variables investigated and survival outcomes after chemotherapy were analyzed via retrospective chart review. RESULTS: In cohort 1, aVAT was significantly correlated with insulin and HOMA-R levels. As body mass index (BMI) class increased, mean IGF-1 increased and mean IGFBP3 decreased, but these trends were not statistically significant. In cohort 2, aVAT was significantly positively correlated with BMI. The patients in the third aVAT tertiles had significantly shorter distant disease-free survival (dDFS) after neoadjuvant chemotherapy setting. In multivariate analysis, aVAT and VAT-HU were significantly associated with shorter dDFS. CONCLUSIONS: High aVAT and low-quality VAT were associated with poor survival outcome, increased insulin levels, and insulin resistance. The present study suggests the importance of evaluating the quality and quantity of VAT when estimating insulin resistance and treatment outcomes.

Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer.

PURPOSE: Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect. METHODS: Plasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2-) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states. RESULTS: Anti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model. CONCLUSIONS: HER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies.

Incidence of Metabolic Syndrome in Young Japanese Adults in a 6-Year Cohort Study: The Uguisudani Preventive Health Large-Scale Cohort Study (UPHLS).

INTRODUCTION: To clarify the incidences of metabolic syndrome (MS) and risks in young Japanese adults by gender. METHODS: A total of 58,901 adults who had undergone annual health check-ups in 2010 without a diagnosis of MS or missing data were divided into three age groups (20s through 40s) by gender. Participants were followed up for 6 years for new-onset MS according to Japanese criteria. The incidences of MS and risks were analyzed using the Cox proportional hazards model to adjust for confounding factors. RESULTS: The incidences of MS per 1,000 person-years were 2.2, 5.5, and 10.2 for women aged in their 20s, 30s, and 40s, respectively, and 26.3, 40.5, and 57.4 in the respective men groups. Compared with the group aged in their 40s, the hazard ratios of new MS were 0.19 (95% confidence interval [CI], 0.13-0.29) for women in their 20s and 0.50 (95% CI, 0.41-0.61) for women in their 30s, and 0.46 (95% CI, 0.42-0.50) and 0.70 (95% CI, 0.66-0.73) for men in their 20s and 30s, respectively, after adjustment for lifestyle factors. For women, MS was associated with smoking in their 20s and 30s, and eating speed in their 30s, and for men, was associated with physical activity, eating speed, alcohol intake in their 20s and 30s, and smoking in their 30s. CONCLUSION: Our findings suggest that the incidences of MS in the 20s and 30s are lower, but account for about 20-50% of women with MS and 50-70% of men with MS in their 40s. However, the data are not negligible and early lifestyle intervention for MS is necessary in young adults.

[Long-Term Outcome of Radiofrequency Ablation Therapy for Breast Cancer].

Although radiofrequency ablation (RFA) is promising for the local treatment of breast cancer, data concerning the longterm results are limited. The present study attempted to evaluate the safety and efficacy of RFA and to clarify patient outcomes after treatment. The study included 26 breast cancer patients treated with RFA between 2006 and 2010. There were no acute complications such as burns. All subjects were followed-up after breast radiation and systemic therapies. At the median follow-up period of 88 months, no local recurrence or distant metastases had occurred. After treatment, a hard lump was formed around the ablated area, which gradually decreased in size in all cases (p<0.001). The lumps were calcified in 9 cases. Nipple retraction persisted in 2 cases. However, it is necessary to recognize that a cosmetic result of RFA was not excellent in all cases, RFA appears to be a safe local treatment technique for breast cancer patients.

Clinical and genetic diagnosis of Cowden syndrome: A case report of a rare PTEN germline variant and diverse clinical presentation.

INTRODUCTION: Cowden syndrome is a rare autosomal dominant disease characterized by the development of hamartomas and increased risks of other tumors, including breast, thyroid, and uterine cancers. Most patients with Cowden syndrome show mutations of the phosphatase and tensin homolog (PTEN) gene on chromosome 10; however, some patients with mutations do not show clinical symptoms, while patients with clinical symptoms may not have detectable PTEN mutations. CASE PRESENTATION: A 39-year-old woman with macrocephaly had previously been diagnosed with Cowden syndrome at another hospital, when she presented with the onset of breast cancer. A wide variety of complications were detected, including cerebellar tumors treated by resection, hydrocephalus, and multiple polyps in the stomach and large intestine. She was further diagnosed with adult-onset Lhermitte-Duclos disease as a complication of Cowden syndrome. She subsequently developed a dural arteriovenous fistula treated by transvenous embolization. After transfer to our hospital, she developed adenomatous goiter treated by resection, recurrent breast cancer treated with hormonal therapy, and multifocal oral mucosal papillomatosis. Her older sister had previously been diagnosed with Cowden syndrome and her father was undiagnosed but had macrocephaly, hydrocephalus, and multifocal oral mucosal papillomatosis, suggestive of Cowden syndrome. After consultation with a genetic specialist, analysis of the PTEN gene showed a rare but likely pathogenic germline c.801 + 2T>A variant located at the splice donor site of intron 7. The patient's clinical diagnosis of Cowden syndrome was accordingly confirmed by the genetic findings. Appropriate surveillance procedures were put in place to detect any further tumors. CONCLUSIONS: The clinical symptoms of Cowden syndrome do not always correlate with the genetic results. However, recent improvements in genetic testing suggest the importance of diagnosing this disease using both clinical and genetic approaches, in collaboration with genetic experts, to ensure an accurate diagnosis and appropriate surveillance for malignant tumors.

Detection of Nonpalpable Tiny Axillary Lymph Nodes Surrounded by Adipose Tissue Using a Near-Infrared Camera.

Background: It is not always possible to detect nonpalpable small lymph nodes (LNs) surrounded by adipose tissue under the wavelength of visible light. A newly developed near-infrared camera with InGaAs element was able to capture photographs using light at >1000-nm wavelength, at which the difference in absorbance between water and lipids is large. This study investigated the ability to detect nonvisible small LNs using light at 1300-nm wavelength. Methods and Results: Following retrieval of LNs through axillary LN dissection from 20 patients with breast cancer, residual specimens were simultaneously photographed using light at 970-, 1070-, 1200-, 1300-, 1450-, and 1600-nm wavelengths. A total of 45 specimens were observed pathologically at the selected portions in which the 1300-nm light was absorbed (high absorbance group [HA group], n = 25) and those in which the 970-nm light was absorbed instead (low absorbance group [LA group], n = 20). All specimens categorized in the HA group detected the LNs, whereas none of those categorized in the LA group detected an LN. The sensitivity and specificity in the identification of an LN were 1.0. The LNs detected using this camera were significantly smaller than those detected by surgeons (3.00 ± 2.93 mm vs. 5.90 ± 3.91 mm, p < 0.01). Discussion: The light at 1300-nm wavelength was absorbed by axillary LNs. This camera detected LNs that were undetectable by surgeons. This novel technology may be applied to lymphatic microsurgery and contribute to the development of a minimally invasive LN dissection method.

Histological features of skin and subcutaneous tissue in patients with breast cancer who have received neoadjuvant chemotherapy and their relationship to post-treatment edema.

BACKGROUND: Lymphedema is a major complication of treatment for breast cancer. Although chemotherapy can cause lymphedema, there have been few reports about histological changes in skin and subcutaneous tissue after chemotherapy. The aim of our study was to determine whether chemotherapy affects blood and lymphatic vessels in the skin and subcutaneous fat and to investigate the relationship between these changes and extent of post-chemotherapy edema. METHODS: We compared histological findings in skin and subcutaneous fat of mastectomy specimens from 38 patients who had received NAC (neoadjuvant chemotherapy) and 56 who had not (non-NAC) attending our institution from 2007 to 2016. Patients whose tumor may have affected the area examined were excluded. Blood and lymphatic vessels were identified by CD31 and D2-40, respectively. We assessed microvessel density (MVD), lymphatic microvessel density (MLVD), lumen cross-sectional area (LA), and amount of endothelium (AE) in blood and lymphatic vessels. To minimize surgical effects, we measured edema, defined as ≥ 15% thicker dorsal subcutaneous tissue than baseline, on the contralateral side. RESULTS: MVD, LA, and AE of blood vessels were greater and MLVD not significantly different in the skin of NAC patients than in that of non-NAC patients. MVD was greater and AE of blood vessels less in subcutaneous fat of NAC patients than in that of non-NAC patients. Patients with edema had significantly less AE of blood vessels in skin than did those without it. CONCLUSIONS: These pathological findings can help to identify patients who will develop edema and improve their treatment.

Coexistence of regulatory B cells and regulatory T cells in tumor-infiltrating lymphocyte aggregates is a prognostic factor in patients with breast cancer.

BACKGROUND: Tumors can acquire tolerance to tumor immunity and develop enhanced proliferation. Regulatory B cells (Bregs), whose role in immune tolerance is similar to that of regulatory T cells (Tregs), appear to be involved in tumor immunity. Recently, Bregs were found to induce Tregs against tumor immunity. However, the platform for the coexistence of Bregs and Tregs in cancer patients and its clinical significance remain unclear; thus, they were evaluated in breast cancer patients. METHODS: In 489 breast cancer patients, CD25- and IL10-positive Bregs and Foxp3-positive Tregs were immunohistochemically evaluated in tumor-infiltrating lymphocyte aggregates (TIL aggregates) that consisted of CD19-positive B-cell follicles and CD3-positive T-cell parafollicles. Then the correlations of the localization and existence of these cells with metastasis-free survival (MFS) were evaluated in breast cancer patients. RESULTS: TIL aggregates were observed in marginal regions of tumors in breast cancer patients. In the TIL aggregates, the existence of Bregs was closely related to that of Tregs (p < 0.0001). On multivariate analysis, the coexistence of Bregs and Tregs in TIL aggregates was correlated with MFS in breast cancer patients (p = 0.007). Furthermore, MFS was significantly shorter for patients with the coexistence of Tregs and Bregs in TIL aggregates than in those with Tregs alone without Bregs (p = 0.0475). CONCLUSIONS: The present results suggest that Bregs are related to the induction of Tregs in TIL aggregates and the development of metastasis of breast cancer cells. Bregs are expected to be a new diagnostic and therapeutic target in breast cancer patients.

Dose-finding study of linaclotide in Japanese patients with chronic constipation: A phase II randomized, double-blind, and placebo-controlled study.

BACKGROUND: Based on the previous phase II/III studies of irritable bowel syndrome with constipation (IBS-C) in Japan that demonstrated the efficacy and safety of linaclotide 0.5 mg/d, we evaluated linaclotide at doses of 0.5 mg/d and lower in the treatment of Japanese patients with chronic constipation (CC). METHODS: This was a phase II randomized, double-blind, placebo-controlled, dose-finding study of linaclotide for Japanese patients with CC (n = 382, 64 men, 318 women, age 20-75). After a baseline period of two weeks, patients were randomized to receive placebo (n = 80), or 0.0625 mg (n = 82), 0.125 mg (n = 71), 0.25 mg (n = 73) or 0.5 mg (n = 76) of linaclotide during a two-week treatment period. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency during the first week. Secondary endpoints included complete SBM (CSBM) responder rates and IBS-QOL. Safety and adverse events were also evaluated. KEY RESULTS: The change in SBM frequency during the first week (mean) was 3.89, 3.11, 3.87, and 3.85 for 0.0625 mg, 0.125 mg, 0.25 mg, and 0.5 mg for linaclotide, significantly higher than for placebo (1.91, P < 0.05). The CSBM responder, which is an important parameter, showed the greatest improvement at the 0.5 mg during the 2 week. The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: Our results suggest that 0.0625, 0.125, 0.25, and 0.5 mg/d are effective doses of linaclotide for treating CC in Japanese patients. ClinicalTrials.gov: NCT02425722, supported by Astellas Pharma, Inc.

A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan.

BACKGROUND: Clinical testing was required to verify the effect of linaclotide 0.5 mg/d in patients with irritable bowel syndrome with constipation (IBS-C) in Japan. METHODS: This was a randomized, double-blind, placebo-controlled (Part 1) and long-term, open-label extension (Part 2) study of linaclotide at 60 hospitals and clinics in Japan. Patients with IBS-C diagnosed using Rome III criteria (n = 500) were randomly assigned to linaclotide 0.5 mg (n = 249) or placebo (n = 251) for a 12-week treatment period followed by open-label treatment with linaclotide (n = 324) for an additional 40 weeks. The primary endpoints were the responder rate of global improvement of IBS symptoms and complete spontaneous bowel movement (CSBM) during 12 weeks. The secondary endpoints included responder rates of SBM and abdominal pain/discomfort relief. KEY RESULTS: Part 1: The responder rates for global improvement and for CSBM frequency were significantly higher for linaclotide compared to placebo (P < 0.001). Secondary endpoints including responder rates for SBM and abdominal pain/discomfort relief in the linaclotide group were also significantly greater than those in the placebo group. Part 2: Patients switched from placebo to linaclotide showed similar responder rates for global improvement and CSBM frequency to those in patients who continued to receive linaclotide, supporting sustained efficacy. Diarrhea was seen in 14.5% of patients; all cases were mild or moderate. CONCLUSIONS AND INFERENCES: This study suggests that a linaclotide dose of 0.5 mg is effective and safe for IBS-C patients in Japan.

Phase II study of neoadjuvant anthracycline combined with nanoparticle albumin-bound paclitaxel for human epidermal growth factor receptor 2-negative breast cancer.

Neoadjuvant chemotherapy (NAC) with anthracyclines followed by taxane chemotherapy has become the standard treatment for patients with locally advanced, operable breast cancer. Recently, the efficacy of nanoparticle albumin-bound paclitaxel (nab-PTX) for metastatic breast cancer was reported. However, there are still few studies of a neoadjuvant regimen including nab-PTX. Thus, the present phase II study evaluated the efficacy and safety of 5-fluorouracil, epirubicin and cyclophosphamide (FEC regimen) followed by nab-PTX as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Women with operable HER2-negative breast cancer (clinical stage T1a-4N1-3) received 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days), followed by 4 cycles of nab-PTX at 260 mg/m2 every 21 days. The patients then underwent mastectomy or breast-conserving surgery (BCS). The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included clinical response rate, pathological response rate, BCS rate and safety. A total of 16 patients were evaluated and 3 patients (18%) achieved pCR (1 patient with estrogen receptor-positive cancer and 2 with estrogen receptor-negative cancer). The pCR rate was 12 and 25% in patients with estrogen receptor-positive and -negative cancers, respectively. The clinical response rate was 100% (clinical complete and partial response in 6 and 10 patients, respectively). The BCS rate was 31.25%. Three patients experienced grade 3 neutropenia during FEC therapy, and no grade 3/4 events occurred during nab-PTX therapy. Thus, neoadjuvant therapy with FEC followed by nab-PTX for operable HER2-negative breast cancer was found to be a safe and effective option.

Investigation of the atrial conduction time measured by tissue Doppler imaging at the left atrial appendage and the actual electrical conduction time: consideration of left atrial remodeling in atrial fibrillation patients.

PURPOSE: The atrial conduction time measured by echocardiography using tissue Doppler imaging (TDI) has been reported as a predictive factor of left atrial (LA) remodeling. We investigated the P wave to LA appendage (LAA) conduction time defined by transthoracic echocardiography using TDI (P-LAA TDI), and directly compared the actual LA electrical conduction time determined by the electrophysiological data. Additionally, we confirmed the clinical utility of the P-LAA TDI by examining the relationship to the electroanatomical LA remodeling data. METHODS: Sixty-three AF patients (22 paroxysmal AF, 41 persistent AF) underwent ablation and electroanatomical LA mapping. The P-LAA TDI was measured after the ablation and was compared with the electrophysiological data during sinus rhythm, including the actual electrical conduction time. RESULTS: A strong linear correlation (r = 0.776, p < 0.001, y = 1.28x + 49) was observed between the P-LAA TDI (161 ± 24 ms) and electrophysiological P-LAA time (87 ± 15 ms). The P-LAA TDI was also strongly correlated with the LA volume (173 ± 52 ml, r = 0.632, p < 0.001) and LA conduction velocity index (1.07 ± 0.19 mm/ms, r = -0.735, p < 0.001), but less to the focal anterior-LVA region surface area (2.2 [0.4-5.0] cm2, r = 0.380, p = 0.002). Additionally, a stepwise multiple linear regression demonstrated that both the LA volume and LA conduction velocity index were strongly associated with the value of the P-LAA TDI (p < 0.001). CONCLUSIONS: The P-LAA TDI was useful for estimating the actual electrophysiological conduction time and represented both electrical and anatomical LA remodeling.

An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer.

The aim of the present study was to evaluate the association between changes in the neutrophil-to-lymphocyte ratio and the survival rate, as well as tumor subtype, in recurrent breast cancer. Patients with recurrent breast cancer following surgery were included in this study. NLR was calculated and compared between two time points: Pre-treatment and recurrence. The associations between the longitudinal NLR change, the NLR at the time of recurrence and overall survival following recurrence (OSrec) were evaluated. A total of 89 patients were evaluated. NLR increased by 0.59 at recurrence, as compared with the initial treatment (P<0.05). The triple negative (TN) type demonstrated 4.59 in NLR, which was the highest among the four subtypes at the time of recurrence (P<0.05). The highest change (an increase of 2.0) was observed in TN type cancer (P<0.05). Patients with high NLR upon recurrence demonstrated significantly shorter OSrec rates (P<0.05). On the other hand, patients with an NLR increased by more than a third quartile demonstrated a shorter OSrec rate (P=0.06). When adjusted by covariates, the NLR and tumor subtype were determined to be associated with OSrec (P<0.05). Therefore, an increased NLR predicts survival, even in patients with recurrent breast cancer, and the NLR is potentially useful as an inflammation marker for TN breast cancer.

Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based Internet survey in Japan.

BACKGROUND: Abdominal bloating is a common symptom in patients with irritable bowel syndrome with constipation (IBS-C). However, it is not included among the required items in the Rome III diagnostic criteria for IBS. Little is known about an impact of abdominal bloating seen in patients with IBS-C. Using a large population-based sample, the aim of the present study was to investigate what is the most bothersome symptom in subjects with IBS-C. METHODS: An Internet survey of 30,000 adults drawn from the general public throughout Japan was conducted to identify subtypes of IBS using the Rome III diagnostic questionnaire. Consecutively, the screened subjects with IBS-C and the same number of age- and sex-matched non-IBS subjects who were randomly selected as controls were asked to answer a questionnaire on the degree of anxiety they experienced in their daily lives, thoughts about bowel habit, and their dominant gastrointestinal symptoms together with exacerbation factors (for IBS-C only). RESULTS: The screening survey showed that the prevalence of overall IBS was 16.5 % (female 17.4 %, male 15.5 %) and that 2.8 % met the criteria for IBS-C, 4.5 % for IBS with diarrhea (IBS-D) and 8.2 % for mixed IBS (IBS-M). Seven hundred and fifty-nine of 835 (90.9 %) subjects with IBS-C and 746 of 830 (89.9 %) control subjects completed the consecutive questionnaire. IBS-C subjects felt a higher degree of anxiety in their daily lives (p < 0.01) and considered bowel habit to be an indicator of health (p < 0.01) to a greater extent than control subjects. In IBS-C, the degree of anxiety was significantly associated with abdominal discomfort (p < 0.01), pain (p < 0.01) and bloating (p = 0.02), but not with the frequency of bowel habit (p > 0.1). Abdominal bloating was the most bothersome symptom (27.5 %), which was more likely to occur after a meal (52.2 %), at work/school (29.2 %) and during times of stress (26.8 %). Only 4.5 % of IBS-C subjects reported abdominal pain as the 'most bothersome' symptom. CONCLUSIONS: A large population-based Internet survey suggests that abdominal bloating has a great impact on the daily lives of subjects diagnosed with IBS-C. Not only bowel movement/abdominal pain but also abdominal bloating should be evaluated in patients with IBS-C.

Coved-type ST-elevation during ablation of ischemic ventricular tachycardia.

A coved-type electrocardiogram (ECG) change in Brugada syndrome is suggested to be the result of abnormally delayed depolarization over the right ventricular outflow tract; however, ischemia of the conus branch of the right coronary artery presents the same ECG change. A 63-year-old man with a history of myocardial infarction demonstrated a transient coved-type ECG change during catheter ablation of ventricular tachycardia. The ECG change appeared during left ventricular mapping without any chest symptoms, and recovered spontaneously. A pilsicainide test was negative and a coved-type ECG did not appear during the perioperative or follow-up period.

The influence of the external structures in atrial fibrillation patients: Relationship to focal low voltage areas in the left atrium.

INTRODUCTION: Left atrial (LA) low voltage areas (LVAs) are suggested as an important factor for maintaining atrial fibrillation (AF). The relationship between focal LVAs and anatomical contact is still unclear. METHODS: Thirty paroxysmal AF (PAF) and 30 persistent AF (PsAF) patients underwent high density voltage mapping during sinus rhythm before any radiofrequency applications were performed. The relationship between the LVA (<0.5mV) and contact area (CoA) demonstrated by enhanced CT and the distance to near external structures were investigated. RESULTS: The anterior region, posterior wall and left pulmonary vein (LPV) antrum were the three most frequent LVA sites that corresponded to CoA sites, and LVAs mostly overlapped with CoAs (PAF 47/61: 77%, PsAF 63/74: 85%). In the PAF group, patients with posterior-LVAs had a shorter distance to the vertebrae than those without (2.8 ± 1.1 vs. 4.4 ± 1.9 mm; P=0.0086). The distance to the vertebrae was the only predictive factor of the existence of a posterior-LVA and the cut-off value was ≤2.9 mm (P<0.0001). Similarly, an LPV-LVA also had the same results (2.0 ± 0.5 vs. 2.7 ± 0.8mm, P=0.0127) and the cut-off value was ≤2.6mm (P=0.0391). In contrast, the PsAF patients had no difference in the distance when compared to the existence of an LVA. CONCLUSIONS: Anatomical CoAs demonstrated a spatial relationship to the LVAs in AF patients. In PAF patients, the distance to near external structures in the posterior region was a predictive factor for the existence of an LVA and may have had some influence on maintaining AF, while in PsAF patients no relationship was suggested.