TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

Correlation between a Bedridden Status and the Long-term Outcome in Hemodialysis Patients after Intracerebral Hemorrhaging

Objective The quality of life and activities of daily living (ADL) are generally poor among dialysis patients after intracerebral hemorrhaging, and their precise clinical course remains unclear. In addition, the association between the severity of cerebral hemorrhaging and the long-term prognosis in these patients has not been fully elucidated. This study aimed to evaluate the subsequent prognosis of hemodialysis patients who survived the acute phase of intracerebral hemorrhaging. Methods We included hemodialysis patients who were admitted to Nagasaki University Hospital between 2007 and 2015 for intracerebral hemorrhaging treatment. After excluding cases of in-hospital death, survivors were classified using the 5-point modified Rankin Scale (mRS), which specifically measures the ADL in patients with cerebrovascular diseases. The patients were followed up at the medical facilities to which they were transferred in the same medical zone until 2017. Results Out of 91 patients with cerebral hemorrhaging (65±11 years old, 66% men, hemodialysis duration 108±91 months), 62 survived until discharge. Twenty-one patients died during observation, largely due to infectious diseases, such as sepsis and pneumonia (n=16, 76%). Compared to patients with mRS 0-4 (n=31), those with mRS 5 (n=31) showed a significantly poorer prognosis. The hazard ratio adjusted for age and antiplatelets was 13.7 (95% confidence interval: 3.88-63.7, p<0.001). Conclusion Hemodialysis patients with intracerebral hemorrhaging who were bedridden showed poor outcomes. The major causes of death were infections. Therefore, these patients should be carefully monitored for infections in order to improve their prognosis.     

A neutralizing anti-fibroblast growth factor (FGF) 8 monoclonal antibody shows anti-tumor activity against FGF8b-expressing LNCaP xenografts in androgen-dependent and -independent conditions

BACKGROUNDS: Fibroblast growth factor 8-isoform b (FGF8b) has been detected in human clinical sex-organ related cancers including hormone-refractory prostate cancer. There are, however, few relevant experimental models. A murine monoclonal anti-FGF8 antibody, KM1334, has been shown to neutralize FGF8b and inhibit the growth of androgen-dependent mouse mammary SC-3 cells in vitro and in vivo. In the present study, we evaluated the anti-tumor activity of KM1334 against androgen-dependent and -independent progression of FGF8b-expressing human prostate cancer xenografts. METHODS: FGF8b cDNA was transfected into androgen-dependent human prostate cancer cell line LNCaP, and its xenograft tumors were established subcutaneously in SCID mice with or without castration. KM1334 at the dose of 400 microg/head was injected twice weekly. RESULTS: FGF8b-expressing LNCaP cells secreted FGF8b, showed enhanced level of Erk1/2 phosphorylation, and showed more potent growth properties than mock-expressing cells in vitro and in vivo. KM1334 reduced these properties in vitro, inhibited tumorigenecity in vivo (T/C=0.33), and showed anti-tumor activity against established tumors (T/C=0.47) of FGF8b-expressing cells. FGF8b-expressing LNCaP tumors were androgen-dependent. However, they recurred as androgen-independent FGF8b positive tumors after castration. KM1334 also inhibited the growth of established FGF8b-expressing tumors in the androgen-independent states (T/C=0.47). CONCLUSIONS: These results indicate that humanized monoclonal antibodies, conserving the paratope of KM1334, are a promising candidate for therapy of FGF8b-expressing clinical prostate cancers. Follow-up studies using xenograft models with clinical FGF8b-expressing tumors are required to validate these early findings.     

Sling removal after the Vesica sling and tension-free vaginal tape (TVT) procedures

PURPOSE: We describe our experience of sling removal performed after either the Vesica sling procedure (due to vaginal erosion or at the time of reoperation for recurrent stress incontinence) or the tension-free vaginal tape (TVT) procedure (due to persistent urinary retention). MATERIALS AND METHODS: From May 1997 to December 2002, we performed 19 Vesica sling procedures and 66 TVT procedures for the treatment of urodynamic stress incontinence. In the former procedures, four patients (21%) developed vaginal erosion and underwent total or partial removal of sling material (Hemashield made from bovine-collagen-injected woven polyester). In another three patients, stress incontinence recurred 2-4 years after the Vesica sling procedure, and they underwent total sling removal and the TVT procedure. Before using the urethral pull-down process (UPDP) in TVT procedures, 2 out of 23 patients (8.7%) developed persistent urinary retention and underwent either sling release alone or partial sling removal concomitant with a second TVT procedure. After the introduction of the UPDP, no patient developed urinary retention. RESULTS: Three patients in whom total sling removal was performed due to vaginal erosion after a Vesica sling procedure developed recurrent stress incontinence. One patient who underwent partial sling removal remained continent, but vaginal erosion recurred 2 years later. Patients who had total sling removal and TVT procedures due to recurrent stress incontinence after Vesica sling procedure became continent with an uneventful postoperative course. One patient who underwent transvaginal release of TVT tape (polypropylene mesh) due to urinary retention after the TVT procedure developed recurrent stress incontinence, and the other who underwent partial removal of TVT tape and a second TVT procedure had resolution of urinary retention without recurrence of stress incontinence. CONCLUSION: Prompt and total sling removal should be recommended for vaginal erosion after the Vesica sling procedure. In patients with urinary retention after the TVT procedure, partial removal of TVT tape and a second TVT procedure using the UPDP to prevent overtightness may be a preferable choice to attain both continence and resolution of urinary retention.     

Diagnostic accuracy of a volume-rendered computed tomography movie and other computed tomography-based imaging methods in assessment of renal vascular anatomy for laparoscopic donor nephrectomy

To evaluate the diagnostic accuracy of computed tomography (CT)-based imaging methods for assessing renal vascular anatomy, imaging studies, including standard axial CT, three-dimensional volume-rendered CT (3DVR-CT), and a 3DVR-CT movie, were performed on 30 patients who underwent laparoscopic donor nephrectomy (10 right side, 20 left side) for predicting the location of the renal arteries and renal, adrenal, gonadal, and lumbar veins. These findings were compared with videos obtained during the operation. Two of 37 renal arteries observed intraoperatively were missed by standard axial CT and 3DVR-CT, whereas all arteries were identified by the 3DVR-CT movie. Two of 36 renal veins were missed by standard axial CT and 3DVR-CT, whereas 1 was missed by the 3DVR-CT movie. In 20 left renal hilar anatomical structures, 20 adrenal, 20 gonadal, and 22 lumbar veins were observed during the operation. Preoperatively, the standard axial CT, 3DVR-CT, and 3DVR-CT movie detected 11, 19, and 20 adrenal veins; 13, 14, and 19 gonadal veins; and 6, 11, and 15 lumbar veins, respectively. Overall, of 135 renal vascular structures, the standard axial CT, 3DVR-CT, and 3DVR-CT movie accurately detected 99 (73.3%), 113 (83.7%), and 126 (93.3%) vessels, respectively, which indicated that the 3DVR-CT movie demonstrated a significantly higher detection rate than other CT-based imaging methods (P < 0.05). The 3DVR-CT movie accurately provides essential information about the renal vascular anatomy before laparoscopic donor nephrectomy.     

Clinical pathway for tension-free vaginal mesh procedure: Evaluation in 300 patients with pelvic organ prolapse

Objectives:   To evaluate a clinical pathway of discharge on postoperative day 3 for the tension-free vaginal mesh (TVM) procedure in patients with pelvic organ prolapse (POP).
Methods:   Between May 2006 and December 2007, 305 consecutive women with POP quantification stage 3 or 4 were planned to undergo the TVM procedure in a single general hospital. Excluding five patients with concomitant hysterectomy, a pathway (removal of the indwelling urethral catheter on the next morning, discharge on postoperative day 3) was applied to the remaining 300 patients. The perioperative complications and postoperative hospitalization were prospectively evaluated in this case series.
Results:   Perioperative complications were: bladder injury (11 cases, 3.7%), vaginal wall hematoma (two cases, 0.7%), rectal injury (one case, 0.3%) and temporary hydronephrosis (one case, 0.3%). None needed blood transfusion. The indwelling urethral catheters were removed on the next morning as in the pathway in 287 cases (95.6%), and none required clean intermittent catheterization at home. Postoperative hospitalization was within 3 days in 280 cases (93.3%). The six cases (2.0%) with longer hospitalization were due to complications (two cases of bladder injury, one of rectal injury, one of blood loss over 200 mL, one of temporary urinary retention, and one of hydronephrosis). Two patients were re-hospitalized within one month due to vaginal bleeding or gluteal pain.
Conclusions:   Patients generally accepted the pathway of discharge on postoperative day 3 in spite of the Japanese culture preferring a longer hospital stay.     

CD133 Expression at the Metastatic Site Predicts Patients’ Outcome in Colorectal Cancer with Synchronous Liver Metastasis

Background

CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods

CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results

CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133? patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions

Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133? patients had a significantly higher rate of extrahepatic recurrence.

     

Cross-modal binding and activated attentional networks during audio-visual speech integration: a functional MRI study

We evaluated the neural substrates of cross-modal binding and divided attention during audio-visual speech integration using functional magnetic resonance imaging. The subjects (n = 17) were exposed to phonemically concordant or discordant auditory and visual speech stimuli. Three different matching tasks were performed: auditory-auditory (AA), visual-visual (VV) and auditory-visual (AV). Subjects were asked whether the prompted pair were congruent or not. We defined the neural substrates for the within-modal matching tasks by VV-AA and AA-VV. We defined the cross-modal area as the intersection of the loci defined by AV-AA and AV-VV. The auditory task activated the bilateral anterior superior temporal gyrus and superior temporal sulcus, the left planum temporale and left lingual gyrus. The visual task activated the bilateral middle and inferior frontal gyrus, right occipito-temporal junction, intraparietal sulcus and left cerebellum. The bilateral dorsal premotor cortex, posterior parietal cortex (including the bilateral superior parietal lobule and the left intraparietal sulcus) and right cerebellum showed more prominent activation during AV compared with AA and VV. Within these areas, the posterior parietal cortex showed more activation during concordant than discordant stimuli, and hence was related to cross-modal binding. Our results indicate a close relationship between cross-modal attentional control and cross-modal binding during speech reading.     

Follow-up for patients with obstructive sleep apnea syndrome using a portable recording device

A home screening device, LT-200, can record data on both breathing conditions and body positions during sleep for up to 3 consecutive days in patients with obstructive sleep apnea (OSAS). We investigated the usefulness of the LT-200 device for follow-up of OSAS. Eighteen patients (age 51.0 +/- 10.8 years, mean +/- SD) were enrolled in this study. Standard polysomnography (PSG) was performed on all patients. The number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI), the total time that nocturnal oxygen saturation was < 90% (oxygen desaturation time: ODT), and the minimum oxygen saturation during sleep (lowest Spo2) were calculated. We used the LT-200 and PSG to evaluate any improvement in the data obtained after auto-continuous positive airway pressure (auto-CPAP) therapy. AHI was also measured using the LT-200 in three sleep positions to evaluate the efficacy of the lateral position. AHI, ODT, and lowest Spo2 values did not differ significantly between the PSG and LT-200 recordings on the control and therapy nights. The LT-200 recordings showed that AHI, ODT, and lowest Spo2 tended to be better on the second night of auto-CPAP therapy than on the first. AHI was significantly lower in the right and left lateral sleep positions than that in the supine position. Our findings suggest that since the LT-200 device provides important information about the severity of OSAS, the efficacy of auto-CPAP therapy, and body position under unattended conditions in the home. It may prove to be a useful tool for following up patients.