No Recurrence Research Articles

Data-Driven Surveillance Protocol for Patients at Risk for Peritoneal Recurrence of Primary Colon Cancer: Surveillance for Peritoneal Carcinomatosis.

Peritoneal carcinomatosis (PC) is rarely discovered early due to low sensitivity of screening imaging and tumor markers, however, earlier identification may improve outcomes. This study assesses risk factors and time to recurrence of PC and implementation of a surveillance system. Patients with stage II-III colon adenocarcinoma undergoing curative colectomy between 2005-2022 were retrospectively reviewed at a single tertiary care institution. Patients were divided into three cohorts: no recurrence (NR), PC, and other types of recurrence (OTR). Baseline characteristics between cohorts were compared with univariate analysis. Overall survival and PC risk were assessed using multivariate analysis with Cox's proportional-hazard modelling. 412 patients were included; 78.4% had NR, 7.8% had PC, and 13.8% had OTR. Patient demographics, comorbidities, tumor side, and histologic features were similar between cohorts. Patients with PC were more likely to have microscopic tumor perforation (25% vs. 8.8% vs. 6.8%, p = 0.002), margin involvement (25% vs. 8.8% vs. 4.6%, p < 0.001), lymphovascular invasion (56.2% vs. 33.3%, vs. 24.5%, p < 0.001), perineural invasion (28.1% vs. 15.8% vs. 11.5%, p = 0.026) compared to OTR or NR. Median time to PC after colectomy was 11 months. Tumor characteristics of stage II-III colon cancer define a high-risk profile for PC. An early surveillance program sensitive for peritoneal disease should be adopted for these patients.

Abstract 10888: Toward a Framework for Comparing Inducibility of Reentrant Arrhythmia in Patient-Specific Computational Models to Clinical Atrial Fibrillation Phenotypes

Introduction: Computational models that incorporate patient-specific left atrial (LA) anatomy and fibrosis from LGE-MRI can assess in silico arrhythmia inducibility in atrial fibrillation (AF) patients. Modeling currently relies on a one-size-fits-all approach for electrophysiological properties, limiting the agreement between simulations and patient outcomes. Hypothesis: Personalization of conduction velocity (ϴ) in computational models of LA fibrosis-mediated arrhythmia derived from persistent AF (PsAF) patients could improve simulation agreement with clinical arrhythmias. Methods: PsAF patients (n=37) were followed ≥2 years after ablation to determine outcomes: AF recurrence, atrial flutter (AFL)-recurrence, or no recurrence (NR). Patient-specific LA models (n=74) were constructed using pre- and ≥90 days post-ablation MRI. Simulated pacing gauged in silico arrhythmia inducibility due to AF-like rotors or AFL-like macro-reentrant tachycardias (MTs). A range of possible ϴ values was tested (±10 or 20%; baseline: non-fibrotic, 71.5 cm/s; fibrotic, 47.0 cm/s). Pre-ablation models were deemed to agree if pacing induced ≥1 rotor or MT; post-ablation models agreed if pacing induced ≥1 rotor, MT, or neither in AF, AFL, or NR patients, respectively. Results: Fifteen patients recurred with AF and 6 with AFL (57% overall). Arrhythmia was induced in 1078/5550 simulations. Using baseline ϴ, model/clinical agreement was 46% (34/74 models), improving to 65% (48/74) when all ϴ values were considered (p=0.031, Fisher’s exact test, Fig. A). ϴ modulation improved model/clinical agreement in both pre- and post-ablation models (Figs. B, C). Pre-ablation model/clinical agreement was higher for patients with more LA LGE (&gt;17.2%) or higher BMI (&gt;32.0 kg/m 2 ) (Fig. D). Conclusions: Patient-specific ϴ calibration improved model/clinical agreement by 41%. Improved understanding of factors that influence model ϴ will have immediate clinical implications.

Abstract 12350: Modulation of Fibrosis Arrhythmogenicity Improves the Accuracy of Patient-Specific Computational Modeling in Persistent Atrial Fibrillation

Introduction: Computational models incorporating left atrial (LA) anatomy and fibrosis from MRI can identify post-ablation recurrence mechanisms in persistent atrial fibrillation (PsAF) patients. However, model accuracy is limited since fibrosis arrhythmogenicity (FA) is simulated identically across all models. Hypothesis: In each model, there exists an optimal FA level such that pre- and post-ablation simulation behaviors match the corresponding patient’s clinical outcome. Methods: 50 LA models were constructed from pre- and ≥90 days post-ablation late gadolinium enhanced MRI in 25 PsAF patients. Virtual pacing was used to probe for arrhythmia inducibility due to AF-like reentrant drivers (RD; i.e., rotors) or atrial flutter (AFL)-like macro-reentry (MR). FA variability was modeled in all patients by altering conduction velocity (CV) ±10% vs baseline (71.5cm/s). No recurrence (NR) was defined as ≥2 years arrhythmia-free. Pre-ablation, accuracy was assessed by confirming ≥1 RD was inducible; post-ablation models for patients with AF, AFL, or NR were screened for RD, MR, or non-inducibility, respectively. Results: At baseline FA, 26/50 (52%) models had simulations matching clinical outcome. When simulations with modulated FA were added, 36/50 (72%) models had simulations matching clinical outcome (Fig A; two-sample proportion t-test, p=0.034). FA modulation improved accuracy in three scenarios: eliminating non-inducible pre-ablation models; unmasking RD inducibility in post-ablation models for patients with AF recurrence; and abolishing inducibility in post-ablation models for NR patients (activation maps shown in Figs B-D, respectively). Conclusion: Modulation of FA in computational models of PsAF improved correlation between simulation behavior and clinical outcomes. This suggests that if FA can be quantified pre-ablation (e.g., via biomarker assay), it could create a new paradigm for model personalization with improved accuracy.

Role of Ki-67, MRE11, and PD-L1 as Predictive Biomarkers for Recurrence Pattern in Muscle-invasive Bladder Cancer.

Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC. Our institutional cystectomy database containing cases from 1992-2014 was queried for patients with local only recurrence (LOR), and case-matched to patients with distant recurrence (DR) and no recurrence (NR). Clinicopathological data were collected and a tissue microarray was analyzed for presence of Ki-67, MRE11, and PD-L1 using immunofluorescence and immunohistochemistry. Pathologic specimens from 42 patients (18 NR, 16 LOR, and 8 DR) were reviewed. Compared to normal bladder tissue, tumors had increased expression of Ki-67 (p<0.01) and PD-L1 (p<0.05). High Ki-67 was associated with recurrence pattern (local vs. distant) on univariate analysis (p<0.05). Ki-67 cell density varied by recurrence type: LOR (1354 cells/mm2), DR (557 cells/mm2) and NR (1111 cells/mm2) (p=0.034). Our selected biomarkers could distinguish MIBC from normal bladder tissue but could not classify samples by recurrence pattern.

Distinct transcriptional profiles in plasma exosomes associated with recurrence of nasopharyngeal carcinoma patients with standard treatment.

6534 Background: Nasopharyngeal carcinoma (NPC) is endemic with a high prevalence in Southern China, Asia,cetuximab and North Africa. Exosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. In the progression of NPC, the tumor cells constantly release exosomes into the surrounding environment and also into the circulating blood. The aim of this study was to explore the association between RNA expression in plasma exosomes and prognosis of NPC patients after standard treatment. Methods: In this retrospective study, a total of 25 eligible NPC patients were included: 12 patients in the recurrence (R) subgroup and 13 patients in the no recurrence (NR) subgroup. RNA was extracted from the exosomes of plasma specimens which were collected at West China Hospital, Sichuan University. Gene expression profiles were conducted by using the RNA-sequencing platform. The DESeq2 package was used to analyze the differentially expressed genes (DEGs) between R and NR subgroups. The gene set variance analysis (GSVA) was performed to explore C5 gene sets enrichment related to the recurrence after standard treatment. Results: We observed 332 DEGs between R and NR subgroups, which include 125 up-regulated and 207 down-regulated genes (R vs. NR,∣log2fold change∣&gt;1, p&lt;0.05). Moreover, hierarchical clustering analysis of the 332 DEGs revealed that all samples clustered into two subgroups, with cluster 1 containing 82% (9/11) recurrence patients and cluster 2 containing 79% (11/14) no recurrence patients. Further, univariate Cox regression analysis showed that 293 out of 332 DEGs were significantly correlated with DFS ( p&lt;0.05), such as TRAM1, CAPN1, SAT1 and ACTB. GSVA and Log Rank test of survival data demonstrated that a total of 824 pathways/biological processes were significantly different between R andNR subgroups ( p&lt;0.05). Specifically, the top 9 pathways/biological processes, such lipoxygenase pathway, rough endoplasmic reticulum membrane and low density lipoprotein particle clearance, was mainly enriched in the NR subgroup ( p &lt;0.001). Conclusions: Profiling of plasma exosomes RNA in NPC patients reveals distinctive gene expression pattern between patients with or without recurrence. Further functional analysis revealed that top enriched 9 pathways/biological processes may correlate with a favorable prognosis and are worth investigating. Moreover, for the prognosis of patients with NPC, RNA expression of plasma exosomes may be a potentially valuable research object.

A Preliminary Study of NER and MMR Pathways Involved in Chemotherapy Response in Bladder Transitional Cell Carcinoma: Impact on progression-free survival.

One of the main genotoxic drugs used in bladder cancer chemotherapy is cisplatin. While it is applied in most types of cancers, resistance to cisplatin is wildly common. In order to overcome drug resistance, it is necessary to determine a predictive marker. This study was conducted to provide basic data for selecting and designing a gene profile for further cohort and RCT studies in the future to improve response to treatment in bladder cancer. The expression levels of ERCC1, MLH1, MSH2, and CTR1 mRNA were determined in the tumor tissue using real-time q-PCR. Progression-free survival (PFS) was analyzed in term of the level of genes expression. The results revealed that the level of ERCC1 mRNA expression was higher in the recurrence (R) group compared to the no recurrence (NR) group. Moreover, the PFS time was increased in the patients with an ERCC1 expression level of below 1.57. The level of MLH1 and MSH2 mRNA expression was lower in the R group compared to the NR group; therefore, PFS time was increased in the patients with MLH1 and MSH2 gene expression levels above the cutoff point. While the level of CTR1 mRNA expression was higher in the R group versus the NR group, the PFS time was longer in the patients with CTR1 expression levels of below 1.265 compared to the patients with high levels of CTR1 expression. It can be concluded that the level of ERCC1, MLH1, MSH2, and CTR1 mRNA expression may be associated with PFS time as possible therapeutic targets for decreasing cisplatin resistance.

Machine Learning in Prediction of Second Primary Cancer and Recurrence in Colorectal Cancer.

Background: Colorectal cancer (CRC) is the third commonly diagnosed cancer worldwide. Recurrence of CRC (Re) and onset of a second primary malignancy (SPM) are important indicators in treating CRC, but it is often difficult to predict the onset of a SPM. Therefore, we used mechanical learning to identify risk factors that affect Re and SPM.Patient and Methods: CRC patients with cancer registry database at three medical centers were identified. All patients were classified based on Re or no recurrence (NRe) as well as SPM or no SPM (NSPM). Two classifiers, namely A Library for Support Vector Machines (LIBSVM) and Reduced Error Pruning Tree (REPTree), were applied to analyze the relationship between clinical features and Re and/or SPM category by constructing optimized models.Results: When Re and SPM were evaluated separately, the accuracy of LIBSVM was 0.878 and that of REPTree was 0.622. When Re and SPM were evaluated in combination, the precision of models for SPM+Re, NSPM+Re, SPM+NRe, and NSPM+NRe was 0.878, 0.662, 0.774, and 0.778, respectively.Conclusions: Machine learning can be used to rank factors affecting tumor Re and SPM. In clinical practice, routine checkups are necessary to ensure early detection of new tumors. The success of prediction and early detection may be enhanced in the future by applying “big data” analysis methods such as machine learning.

Predictors of postoperative early recurrence of extrahepatic bile duct cancer.

Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer. Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared. Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1year, p < 0.01, respectively). Multivariate analysis showed that age > 75years, serum CA19-9 > 1008U/ml and perineural invasion were independent predictors of early recurrence. High serum CA19-9 values (>1008U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.

Can Bladder Cancer Biomarkers from Patients Undergoing Cystectomy Predict the Need for Adjuvant Radiotherapy?

There is a high rate of recurrence of muscle-invasive bladder cancer (MIBC) after cystectomy with local recurrence rates of about 40% and up to 50% distant recurrence. Currently, the inability to predict recurrence patterns limits the use of adjuvant radiotherapy. The ability to use biomarkers to predict local vs distant recurrence could individualize adjuvant therapy. This study evaluates the ability of PD-L1, MRE11 and Ki67 labeling index in radical cystectomy specimens to predict recurrence (no recurrence (NR), local-only recurrence (LOR), and distant recurrence (DR)) in those with MIBC. Our institutional radical cystectomy (RC) database, which includes 2405 cases of urothelial MIBC from 1/1992-12/2014, was queried for LOR. This yielded 119 patients. Of these, pathologic confirmation of disease was available on 20 patients. These were case-matched to 20 NR patients and 20 DR patients. Those without tissue for biomarker staining or adequate follow-up data were excluded. Representative tumor specimens were selected based on H&E slides. Normal bladder tissue adjacent to areas of tumor from RC specimens was also evaluated. A tissue microarray (TMA) was built from formalin fixed, paraffin embedded tissue and analyzed for presence of MRE11, PD-L1 and Ki67 antibodies via immunofluorescence and immunohistochemistry (PD-L1 and Ki67 only). We evaluated pathologic specimens of 42 patients (18 NR, 16 LOR, and 8 DR). The median age of the patients was 69 years. 81% had pT3/pT4 disease, 36% were pN0, and 14% had positive margins. Median follow-up was 147 months. Compared to normal bladder tissue, urothelial cancer cells had higher PDL1 H score, Ki67 H score, % Ki67 on IHC, MRE11 positive cells, MRE11 positive cell density, PD-L1 positive cells, and PD-L1 positive cell density. On univariate analysis, positive surgical margins were more likely to have PD-L1 CPS score >10 and a lower mean Ki67 H score, Ki67 percentage on IHC, PD-L1 positive cells, %PD-L1 positive cells and PD-L1 cell density. Patients with DR had a significantly lower Ki67 mean positive cells (IF) than those with LOR (p=0.04). PD-L1 H score, PD-L1 positive cells and % positive PD-L1 cells were significantly correlated with RFS (p= 0.008, 0.018, 0.015, respectively). On multivariable analysis (MVA), none of the three biomarkers were correlated with LOR/DR, RFS, or OS. PD-L1, MRE11, and Ki67 could discriminate cancer cells from noncancer cells but were unable to predict types of recurrence or clinical cancer outcomes on MVA. Further studies with larger sample size are required to examine the relationship between these biomarkers and bladder cancer recurrence.

Does Coronal Knee and Ankle Alignment Affect Recurrence of the Varus Deformity after High Tibial Osteotomy?

PurposeThe purpose of this study was to evaluate changes in the coronal alignment of the knee and ankle joints after open wedge high tibial osteotomy (OWHTO) to determine factors related to the recurrence (R) of the varus deformity by serial analysis.Materials and MethodsSixty-four OWHTOs were enrolled in this study. The weight bearing line (WBL) ratio, joint line convergence angle (JLCA), knee joint inclination, mechanical axis-tibial plateau angle, talar inclination (TI), and distal tibia articular angle (DTAA) were serially assessed. Serial correlation analysis between all parameters was performed. Patients were divided into R group and no recurrence (NR) group according to the WBL ratio (55%) at postoperative one year.ResultsThe preoperative WBL ratio showed significantly negative correlation with serial changes of JLCA, TI, and DTAA (p<0.05). The JLCA, TI, and DTAA as well as WBL ratio showed a significantly larger degree of varus alignment in the R group than in NR group at postoperative 6 weeks and 1 year after OWHTO (p<0.05).ConclusionsSufficient correction of the WBL and restoration of the JLCA during OWHTO are essential to prevention of the R of varus deformity after the surgery because they are the only modifiable factors during surgery.Level of EvidenceIV, Case series

MicroRNA‐125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection

Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non-cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1year of resection as the early recurrence (ER) group, patients who had a recurrence within 1-5years as the late recurrence (LR) group, and patients who did not recur during the 5-year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. Multivariate analysis revealed that α-fetoprotein >31ng/mL, tumor size >4cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)-125b-5p and miR-148a-3p were significantly downregulated in recurrent cases. The ratio of miR-125b-5p expression in cancerous versus non-cancerous tissue (miR-125b ratio), but not miR-148a-3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR-125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR-125b ratio and IM were independently associated with ER and disease-free survival. Assessing tissue miR-125b-5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection.

Predictive Independent Factors for Extrahepatic Metastasis of Hepatocellular Carcinoma Following Curative Hepatectomy.

The aim of this study was to investigate the prognostic factors associated with extrahepatic metastasis of primary hepatocellular carcinoma (HCC). We retrospectively analyzed 559 patients with HCC who underwent curative hepatectomy. We divided the patients into no recurrence (NoR), intrahepatic early recurrence (IHER), intrahepatic late recurrence (IHLR), and extrahepatic recurrence (EHR) groups. We compared the non-metastatic group (IHLR and NoR) with the metastatic group (IHER and EHR) and also compared IHER with EHR to determine risk factors for EHR. There were 252, 163, 109, and 35 patients with NoR, IHER, IHLR, and EHR, respectively. For the EHR group, the independent risk factor was vascular invasion. The EHR group had better liver function and worse tumor factors. Vascular invasion is predictive of extrahepatic metastasis of HCC.

MP90-14 DOES SATURATION INDEX PREDICT STONE ACTIVITY IN PATIENTS WITH CALCIUM OXALATE NEPHROLITHIASIS?

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy1 Apr 2017MP90-14 DOES SATURATION INDEX PREDICT STONE ACTIVITY IN PATIENTS WITH CALCIUM OXALATE NEPHROLITHIASIS? Noah Canvasser, Aaron Lay, Elysha Kolitz, Beverley Huet, Xilong Li, John Poindexter, Jodi Antonelli, and Margaret Pearle Noah CanvasserNoah Canvasser More articles by this author , Aaron LayAaron Lay More articles by this author , Elysha KolitzElysha Kolitz More articles by this author , Beverley HuetBeverley Huet More articles by this author , Xilong LiXilong Li More articles by this author , John PoindexterJohn Poindexter More articles by this author , Jodi AntonelliJodi Antonelli More articles by this author , and Margaret PearleMargaret Pearle More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2833AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Equil 2 has been the gold standard for estimation of urinary saturation of stone-forming salts (relative saturation ratio, RSR). The Joint Expert Speciation System (JESS) is an alternative, perhaps superior, computer program that takes into account soluble complexes that Equil 2 does not and is thought to be a more accurate estimation of supersaturation (saturation index, SI). While RSR is often provided in 24-hour urine analyses, the clinically relevant impact of these estimations of supersaturation on stone activity is not well studied. Our goal was to determine if SI CaOx correlates with stone activity in calcium oxalate (CaOx) stone formers. METHODS We reviewed the charts of 604 patients from our stone clinic between 2005 and 2016 and identified CaOx stone formers who had a baseline 24-hour urine collection and at last one follow-up urine collection after the initiation of drug and/or dietary therapy. Patient demographics, imaging studies, serum chemistries, and 24-hour urine studies were recorded in a timeline for each patient. SI was calculated using JESS for each 24-hour urine study. Stone recurrence (SR) was defined as stone growth or new stone formation and no recurrence (NR) indicated no new stone formation. Absolute SI values were compared between times of SR and times of NR, and change in SI from baseline to time of SR were correlated with SI. Statistical analysis was performed with SAS, and significance was set at p<0.05. RESULTS In total, 255 patients with 358 events were included in the analysis. Mean patient age was 51 ± 13 SD years, with a male:female ratio of 1.3. Comparing NR (98 patients with 97 events) to SR (157 patients with 113) demonstrated no significant difference in mean SI CaOx values (5.6 ± 2.8 versus 5.6 ± 2.9, p=0.6). In addition, in patients who experienced SR (n=157) no significant difference was seen comparing mean SI CaOx values during NR (n=148) or SR (n=113) events (5.9 ± 2.8 versus 5.6 ± 2.9, respectively, p=0.08). For all patients with SR, 65 were identified who experienced both changes from SR to NR (median ΔSI CaOx 0.20, IQR -1.46-1.21) and NR to SR (median ΔSI CaOx 0.52, IQR -1.55-1.47). No significant difference was seen (p=0.84). CONCLUSIONS At first evaluation, neither absolute nor change in SI correlates with stone recurrence and may not be a reliable way to follow effectiveness of medical therapy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1215-e1216 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Noah Canvasser More articles by this author Aaron Lay More articles by this author Elysha Kolitz More articles by this author Beverley Huet More articles by this author Xilong Li More articles by this author John Poindexter More articles by this author Jodi Antonelli More articles by this author Margaret Pearle More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Persistent left atrial remodeling after catheter ablation for non-paroxysmal atrial fibrillation is associated with very late recurrence

BackgroundThis study aimed to evaluate the association between left atrial (LA) structural remodeling and very late recurrence [VLR; initial recurrence >12 months after catheter ablation (CA)] after successful CA for non-paroxysmal atrial fibrillation (AF). MethodsWe retrospectively evaluated 63 patients who underwent initial, single ablation for drug-refractory persistent or long-standing persistent AF and those who had no recurrence in the first year after CA. We followed patients for a mean of 3.2±1.5 years and divided them into VLR and no-recurrence (NR) groups. Before and 3 months after ablation, all patients were subjected to 64-slice multidetector computed tomography scanning to estimate LA volume, including maximum and minimum volume during the cardiac cycle (LAMaxV and LAMinV, respectively), and the LA emptying fraction. ResultsVLR occurred in 21 patients. The reduction rate of LAMaxV after CA was significantly larger in the NR group than in the VLR group (25±19% vs. 5±18%, p=0.0002). Receiver operating characteristic analysis was performed to determine the best cut-off values in the prediction of VLR. The highest area-under curve was obtained with post-CA LAMinV [0.828 (95% confidence interval, 0.712–0.912), p<0.0001], with a best cut-off value of 44mL (sensitivity 81.0%, specificity 81.0%). ConclusionsPersistent LA structural remodeling after initially successful CA for non-paroxysmal AF may be an important risk factor for VLR.

Outcome of pulmonary vein isolation ablation for paroxysmal atrial fibrillation: predictive role of left atrial mechanical dyssynchrony by speckle tracking echocardiography

Although few clinical variables have been associated with recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) the role of left atrial (LA) mechanical function in the outcome of catheter ablation of AF is not adequately defined. The aim of our study was to determine whether LA mechanical dyssynchrony as evaluated by speckle tracking echocardiography can predict outcome of PVI ablation procedure in patients with paroxysmal AF. Twenty-five patients (age 58 ± 11 years, [mean ± standard deviation], 17 males) with paroxysmal AF who met specific enrollment criteria pertaining to clinical presentation and follow-up, assessment of LA mechanical dyssynchrony, and strategy of catheter ablation procedure were enrolled. For LA mechanical dyssynchrony assessment, the time to peak longitudinal strain (TPk) in opposing walls in the midportion of the LA walls at peak atrial contraction in standard two- and four-chamber echocardiographic views by vector velocity imaging (VVI) was measured. Outcome of PVI procedure, whether no recurrence (NR) or AF recurrence (AFR) after 3 months of post-procedural blanking period, was evaluated based on AF-related symptoms and documentation of AF by electrocardiogram, continuous 24-h Holter, and intermittent event monitor recordings. During a follow-up period of 20.3 ± 8.6 months, 18 out of 25 (72 %) patients had no recurrence (NR group), and 7 out of 25 (28 %) patients had recurrence of AF (AFR group). Significant gender difference was observed in terms of outcome such that all AFR patients were men and no woman had recurrence of AF. Between the NR and AFR groups, neither the left atrial diameter, 4.0 ± 0.3 and 4.2 ± 0.2 cm, respectively (p = 0.2), nor the left atrial volume indexes, 45 ± 15 and 48 ± 20 ml/m(2), respectively (p = 0.56), were statistically significantly different. For LA mechanical function, compared to the patients in NR group who had maximum opposing wall TPk delay of 39.9 ± 12.0 ms, those in the AFR group demonstrated significantly more LA mechanical dyssynchrony with maximum opposing wall TPk delay of 64.4 ± 17.0 ms prior to ablation (p = 0.007). Using receiver operative characteristic analyses of the data that had an area under the curve of 0.865, we identified a maximum opposing wall delay cutoff value of 51 ms which predicted AF recurrence with sensitivity and specificity values of 89 and 72 %, respectively (p = 0.005). Speckle tracking strain analysis echocardiography can evaluate the LA mechanical dyssynchrony quantitatively. The severity of LA mechanical dyssynchrony by VVI can predict the outcome of PVI catheter ablation for paroxysmal AF.

Serological predictors for the recurrence of atrial fibrillation after electrical cardioversion.

Background and ObjectivesAlthough electrical cardioversion (CV) is effective in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF), AF frequently recurs in spite of antiarrhythmic medications. We investigated the predictors of failed CV and AF recurrence after successful CV.Subjects and MethodsIn 81 patients (M:F=63:18, 59.1±10.5 years old) with AF who underwent CV, clinical findings and pre-CV serologic markers were evaluated.ResultsDuring 13.1±10.6 months of follow-up, 8.6% (7/81) showed failed CV, 27.16% (22/81) showed early recurrence atrial fibrillation (ERAF; ≤2 weeks), 32.1% (26/81) had late recurrence atrial fibrillation (LRAF; >2 weeks), and 32.1% (26/81) remained in SR and had no recurrence (NR). Plasma levels of transforming growth factor beta (TGF)-β were significantly higher in patients with failed CV than in those with successful CV (p=0.0260). Patients in whom AF recurred were older (60.4±9.0 years old vs. 55.3±12.5 years old, p=0.0220), and had lower plasma levels of stromal cell derived factor (SDF)-1α (p=0.0105). However, there were no significant differences in these parameters between ERAF patients and LRAF patients.ConclusionPost-CV recurrence commonly occurs in patients aged >60 years and who have low plasma levels of SDF-1α. High plasma levels of TGF-β predict failure of electrical CV.

The Effect of Cystine Level and Urinary PH on the Recurrence of Cystine Stones

Purpose Retrospective review of the medical therapy on pediatric patients with cystin stones as regards recurrence rates. Material and Methods 21 patients (12 boy, 9 girl) under follow-up with cystin stones were retrospectively evaluated. Median diagnosis age was 1 year old(range:1-16). Medical therapy was applied with 10 to 15 mg/kg a-mercaptopropionylglycine and 1 mEq./kg potassium citrate or Scholl solution following the initial treatment. Results Surgery was performed on 18 patients (percutaneous nephrolithotomy in 21 sessions on 13 patients, open on 8 patients); ESWL on 12 patients (in 2,7 sessions in the average). All patients received the same medical treatment stated above. Urinary pH levels increased (pretreatment/posttreatment urinary pH were from 6,0± 0.63 to 6.6± 0.59) and cystine levels decreased (from 885±1118 to 322±204mmol./mol. creatinine) after treatment. Being the control urinary pH over 6.5 was observed to be effective in the prevention of recurrences (p=0.02). Recurrence was seen in none of the patients with control urinary system levels under 150. Recurrence significantly lower in patients with control cystine levels under 150 when urinary pH was over 6.5 (p=0.044) (Table). In addition, while recurrence was seen in two patients out of six with high cystine levels and urinary pH over 7, recurrences were seen in six patients out of seven with lower pH values. Table. Effect of urinary pH>=6.5 when cystine levels are high (p=0.044) CYSTINE>150; URINARY pH CYSTINE>150; URINARY pH>=6,5 TOTAL NO RECURRENCE 0 5 5 RECCURENCE + 5 3 8 TOTAL 5 8 13 Conclusions Keeping the control urinary pH above 6.5 for the prevention of cystine stones appears to be effective even in patients with high cystine levels.

Molecular signatures associated with clinical outcome in patients with high-risk head-and-neck squamous cell carcinoma treated by surgery and radiation

The local-regional control rate for advanced head-and-neck squamous cell carcinoma (HNSCC) remains poor and is unpredictable for a given individual. This study examined whether gene expression patterns developed from tumors from surgicopathologic, criteria-defined, high-risk HNSCC patients could be correlated with clinical outcomes, namely, metastasis or nonrecurrent disease. Fifteen primary tumors from patients treated with a consistent protocol of surgery followed by radiotherapy were examined. Seven of these tumors were from high-risk patients who developed distant metastasis (DM), and eight tumors were from patients with no recurrence (NR) (median follow-up, 59 months). Unsupervised clustering of gene expression did not separate the two groups from one another, but when supervised methodologies were applied, 205 genes discriminated the two groups. Within the DM group, genes associated with cell growth and proliferation; DNA replication, recombination, and repair; antiapoptotic pathways; cell adhesion; and angiogenesis were identified. For NR samples, discriminatory genes were associated with the onset of apoptosis. Our data suggest that gene expression analysis of surgically excised HNSCC tumors from patients considered at high risk for recurrence has the potential to identify individuals susceptible to metastasis on the basis of distinct gene-expression patterns. These patients would be ideal candidates for testing systemic therapy.

Expression and induction of heme oxygenase mRNA in rat placenta

s: J.P.G. Japan 1995 EXPRESSION AND INDUCTION OF HEME OXYGENASE mRNA IN RAT PLACENTA. Naomi Ihara, Yuji Hiramatsu, Hiroyuki Okuda, Takahumi Kudo and Reiko Akagi, Department of Obstetrics and Gynecology, Okayama University Medical School, Faculty of Health and Welfare Science, Okayama Prefectural University, Okayama, Japan Heme oxygenase (HO), a rate-limiting enzyme in heme catabolism, cleaves heme to form biliverdin, iron and carbon monoxide (CO). It is thought to function as a defense system against several kinds of stress because of the end product bilirubin which is one of endogenous radical scavengers. Recently it was suggested that CO produced by the HO reaction functions as an endogenous modulator of vascular one. The fact that the fetus lives under hypoxic conditions prompted us to investigate the statistics of HO expression in the placenta and fetal tissues. HO mRNA was detected by Northern blot analysis using biotin labeled specific RNA probe. HO mRNA showed significantly higher levels in placenta compared to other rat fetal tissues and was almost the same level of adult spleen. It increased during pregnancy, reached the highest on the 17th day of gestation. Ligature of uterine vessels resulted in the induction of HO within 2 hours and reached more than two times of the basal level. Our findings suggest that heme might be primarily catabolized in the placenta instead of the spleen during the fetal period and CO produced by the HO reaction may contibute as a modulator of the fetoplacental circulation. A.3 A CASE OF PLACENTAL SITE TROPHOBLASTIC TUMOR (PSTT) WITH NO RECURRENCE FOR 8 YEARS AFTER TREATMENT. Kenichiro Ikuma”, Toshiya Komatsu” and Tadashi Takemura”, Department of Obstetrics and Gynecology” and Division of Pathology”, Takarazuka City Hospital, Hyogo, Department of Obstetrics and Gynecology, Hyogo Medical College’, Hyogo , Japan (Objective) The histological diagnosis of a biopsy specimen was glassy cell carcinoma, Placental site trophoblastic tumor (PSTT) was suspected and later confirmed. We have followed the patient for 8 years and noted no abnormal findings. (Case Report) A 44-year-old woman had had two normal deliveries and two artificial terminations of pregnancy, most recently in 1980. On October 27, 1988, she visited our hospital because of bleeding during coitus. A dark red polyp-like protrusion was seen in the uterine cervix. Cytological and histological examinations led to a definite diagnosis of PSTT. Tumor markers before surgery were within the normal range; hCG, less than 2.0 mIU/ml; ,0 -hCG, less than 0.6 rig/ml; hPL, less than 1 g/ml. (Clinical course) She was admitted to our hospital on December 1, 1988, and abdominal hysterectomy and right adnectomy were performed on December 5. Her postoperative recovery was good, and she was discharged on December 20,1988 after intraperitoneal administration of 80 mg of CDDP. Radiation therapy was started in January 1989. Etoposide was administered orally every other week at a daily dose of 25 mg for 6 months. (Conclusion) Previous reports of PSTT have indicated that the prognosis is relatively poor in patients with many karyokinetic figures and high values of hCG. Further elucidation of the pathophysiology of this disease and the establishment of appropriate therapy are needed, but we believe that surgery is still the best initial therapy.

CASE OF SARCOMA OF THE CHOROID—OPERATION—NO RECURRENCE IN NEARLY THREE YEARS.Read in the Section of Ophthalmology at the Forty-first Annual Meeting of the American Medical Association, held at Nashville, Tenn., May, 1890.

Malignant intra-ocular growths are of so much importance that every case of the kind should be placed on record, and especially the results of treatment, whether favorable or otherwise, in order that we may learn at what stage of development the disease passes beyond the control of remedial measures. I therefore beg to occupy your time briefly with a report of the following case: In June, 1887, I was consulted by Mrs. K., 40 years of age, who reported that three years previously she had lost the sight of her right eye while suffering from symptoms which, according to her description, were very like those of acute glaucoma, and that the organ had continued more or less irritable up to the time of presentation. On examination I found vision extinct; conjunctiva moderately injected; pupil somewhat dilated, and motionless; iris discolored; lens cataractous; tension plus 1; pain in the eye, forehead