Kenta Murotani

Adverse prognostic impact of perioperative allogeneic transfusion on patients with stage II/III gastric cancer

BackgroundAllogeneic blood transfusions (BTFs) are sometimes required for radical gastrectomy with regional lymph node dissection for advanced gastric cancer (GC). The prognostic impact of perioperative BTF in GC is controversial.MethodsClinical data were collected retrospectively from 250 consecutive patients who underwent curative gastric resection for stage II/III GC. The prognostic impact of BTF on patient survival was evaluated. Subgroup analysis was performed according to units of blood transfused, timing of BTF, type of gastrectomy, splenectomy, intraoperative estimated blood loss, and year of surgery.ResultsFifty-seven (22.8xa0%) patients underwent perioperative BTF. Patients who received BTF experienced a significantly shorter disease-specific survival after curative surgery, and multivariable analysis identified perioperative BTF as an independent prognostic factor for cancer-related death (hazard ratio, 1.80; 95xa0% confidence interval, 1.05–3.02; pxa0=xa00.032). The BTF group experienced significantly lower recurrence-free survival rate and a higher rate of initial peritoneal recurrence. The amount of blood cells transfused had less impact on prognosis. Pre- or postoperative BTF without intraoperative BTF had limited influence on postoperative prognosis. Prognosis of patients was affected by splenectomy. Even when intraoperative blood loss exceeded 800xa0ml, the prognosis of the non-BTF group was more favorable. The prognostic impact of BTF became less clear after introduction of adjuvant chemotherapy with S-1.ConclusionsBTF was an independent prognostic factor in patients with stage II/III GC after curative gastrectomy. To improve prognosis, BTF should be avoided when possible, particularly during surgery.

Comparison of the international consensus guidelines for predicting malignancy in intraductal papillary mucinous neoplasms

BACKGROUNDnThis study sought to evaluate the predictors of malignancy in the 2012 international consensus guidelines for intraductal papillary mucinous neoplasms (IPMNs) and validate their diagnostic value relative to the 2006 guidelines.nnnMETHODSnBetween 2002 and 2014, 177 consecutive patients who underwent curative resection of IPMN were reviewed. Based on the 2012 guidelines, high-risk stigmata (mural nodule with enhancement, main pancreatic duct [MPD] ≥ 10 mm, and obstructive jaundice) and worrisome features (cyst size ≥ 30 mm, thickened cyst wall, mural nodule without enhancement, MPD 5-9 mm, an abrupt change in MPD diameter, and lymphadenopathy) were assessed, and predictive and diagnostic values were analyzed statistically.nnnRESULTSnMultivariate analysis identified obstructive jaundice (odds ratio [OR], 23.9; P < .0001), abrupt change in MPD diameter (OR, 3.01; P = .017) and lymphadenopathy (OR, 5.84; P = .027) as independent predictive factors, with an accuracy of 69.8, 67.4, and 66.3%, respectively. Operative intervention was indicated in 156 patients (94.0%) using the 2006 guidelines, and in 130 (78.3%) using the 2012 guidelines. The accuracy of the 2006 guidelines was 35.5% compared with 44.8% for the 2012 guidelines. The area under the curve (AUC) for the 2006 and 2012 guidelines was 0.65 and 0.67, respectively; ΔAUC was 0.02, which was not statistically significant. When the worrisome features were combined with high-risk stigmata, the AUC increased to 0.79.nnnCONCLUSIONnObstructive jaundice, abrupt change in MPD diameter, and lymphadenopathy were independent predictive factors in the 2012 guidelines with high accuracy. Using the new guidelines, the number of patients with IPMN managed with observation and the predictive accuracy increased.

Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients

AIMSnHypersecretion of glucagon and reduced insulin secretion both contribute to hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of impaired glucagon and insulin secretions in glucose excursions at the various stages of T2DM development remain to be determined.nnnMETHODSnThe responses of glucagon and insulin as well as those of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were examined before and after ingestion of glucose or mixed meal in Japanese subjects with normal or impaired glucose tolerance (NGT and IGT) and in non-obese, untreated T2DM of short duration.nnnRESULTSnIn OGTT, T2DM showed a rise in glucagon at 0-30 min, unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a rise in glucagon at 0-30 min, with that in T2DM being highest, while T2DM showed a significant reduction in insulin. Linear regression analyses revealed that glucose area under the curve (AUC)0-120 min was associated with glucagon-AUC0-30 min and insulin-AUC0-30 min in both OGTT and MTT. Total and biologically intact GIP and GLP-1 levels were similar among the three groups.nnnCONCLUSIONSnDisordered early phase insulin and glucagon secretions but not incretin secretion are involved in hyperglycemia after ingestion of nutrients in T2DM of even a short duration.

Sex-Related Differences in Ocular Blood Flow of Healthy Subjects Using Laser Speckle Flowgraphy.

PURPOSEnTo evaluate sex-related differences in ocular blood flow of healthy subjects using laser speckle flowgraphy (LSFG).nnnMETHODSnIn this prospective cross-sectional study, we examined 103 healthy volunteers (47 males, 56 females; mean age: 39.3 ± 15.6 years and 42.1 ± 18.7 years, respectively). The blood flow to the optic nerve head (ONH) and choroid was assessed with LSFG, including mean blur rate (MBR) and pulse waveform variables. We evaluated sex-related differences in these variables and compared them with those in other clinical parameters.nnnRESULTSnA linear single regression showed that the ONH-MBR (r = -0.402, P < 0.001) and five ONH pulse waveforms were significantly correlated with sex. A multiple stepwise regression analysis revealed that sex (β = 0.389, P < 0.001) and age (β = -0.290, P = 0.002) were independent factors, indicating the ONH-MBR, age (β = -0.394, P < 0.001), and subfoveal choroidal thickness (β = 0.221, P = 0.016) were independent factors indicating the choroidal MBR. Moreover, sex was an independent factor indicating the five ONH pulse waveform parameters that were consistent with results of the linear single regression. The optic nerve head MBR in the female group was significantly higher than that in the male group (P < 0.001), but no differences were observed in the choroid between the groups (P > 0.05).nnnCONCLUSIONSnSex-related differences are present in ocular blood flow in the ONH, but not in the choroid in healthy subjects. We believe that these differences should be considered when interpreting blood flow data in ocular diseases.

Decreased expression of prenyl diphosphate synthase subunit 2 correlates with reduced survival of patients with gastric cancer

BackgroundIdentification of novel molecular biomarkers will improve the management of patients with gastric cancer (GC). Prenyl diphosphate synthase subunit 2 (PDSS2) is required for coenzyme Q10 biosynthesis and acts as a tumor suppressor; however, the role and regulatory mechanisms of PDSS2 in GC are not understood. The aim of this study was to determine expression status and regulatory mechanisms of PDSS2 in GC.MethodsAssociations between expression and methylation of PDSS2 were evaluated using GC cell lines. The clinical significance of PDSS2 expression was evaluated using 238 pairs of surgically resected gastric tissues with subgroup analysis based on GC subtypes.ResultsThe expression of PDSS2 mRNA was decreased in 73% of GC cell lines compared with the control non-cancerous cell. The PDSS2 promoter was hypermethylated in cells with decreased PDSS2 expression, and treating these cells with a methylation inhibitor reactivated PDSS2 expression. GC tissues expressed significantly lower mean levels of PDSS2 mRNA compared with adjacent normal tissues (P <0.001). The expression pattern of PDSS2 protein was consistent with that of its mRNA. The decrease of PDSS2 mRNA expression in GC tissues (less than half the level of expression detected in the corresponding normal adjacent tissues) correlated significantly with elevated levels of carbohydrate antigen 19-9 (P = 0.015), lymph node metastasis (P = 0.022), and shorter recurrence-free survival after curative resection (P = 0.022). Further, multivariate analysis identified PDSS2 mRNA expression as an independent prognostic factor (hazard ratio 1.95, 95% confidence interval 1.22–3.09, P = 0.005), and its expression pattern and prognostic significance were similar among three GC subtypes.ConclusionsPDSS2 encodes a putative tumor suppressor, and we show here that its expression was regulated by hypermethylation of its promoter in GC cells. Inhibition of PDSS2 mRNA expression may serve as a novel biomarker of all types of GC.

The effects of combine treatment of memantine and donepezil on Alzheimer's Disease patients and its relationship with cerebral blood flow in the prefrontal area

In this study, we evaluated the effect on cognitive function of memantine, behavioral and psychological symptoms of dementia, and the care burden, in patients with moderate‐to‐severe Alzheimers disease (AD). Furthermore, with near‐infrared spectroscopy (NIRS), we examined the association between effect of memantine and brain blood flow.

Vein resections >3 cm during pancreatectomy are associated with poor 1-year patency rates

BACKGROUNDnResection of the superior mesenteric vein (SMV) and portal vein (PV) involved in pancreatic neoplasms improves the chances of complete tumor removal. No consensus exists, however, on the optimal reconstructive approach, and postoperative venous stenosis in the first 6 months to 1 year can cause patient morbidity. We investigated medium-term patency after direct, end-to-end venous anastomosis and evaluate predictive factors for stenosis or occlusion.nnnMETHODSnWe analyzed retrospectively the records of 810 patients who underwent pancreatectomy at our institution from January 2000 through April 2014, and 197 patients who underwent concurrent SMV/PV resection were selected. The venous anastomosis was assessed every 4 or 6 months postoperatively by the use of portography with computed tomography. Preoperative and intraoperative variables were evaluated for their possible association with the development of severe anastomotic stenosis (≥70% occlusion).nnnRESULTSnAmong patients whose cancer did not recur during the 1-year follow-up period, 18 developed severe stenosis. Univariate analyses showed that operation time ≥520 minutes and length of SMV/PV resection ≥31 mm were associated with the development of severe anastomotic stenosis. Multivariate analysis showed that length of SMV/PV resection ≥31 mm was among independent predictors of medium-term, severe anastomotic stenosis (hazard ratio, 5.96; 95% confidence interval 1.79-22.69; P = .003).nnnCONCLUSIONnDirect end-to-end anastomosis of the PV system is safe and offers patients with periampullary neoplasia improved chances of complete tumor excision. When tension-free anastomosis cannot be guaranteed, generally in cases requiring ≥31 mm of SMV/PV resection, venous autografting may decrease the likelihood of anastomotic stenosis.

Long-term results of pulmonary vein antrum isolation in patients with atrial fibrillation: an analysis in regards to substrates and pulmonary vein reconnections

AIMSnTo examine the impact of left atrial (LA) low-voltage zones (LVZs) on atrial fibrillation (AF) recurrence after pulmonary vein antrum isolation (PVAI) without LA substrate modification.nnnMETHODS AND RESULTSnSeventy-six patients with AF (paroxysmal/persistent 65/11) were prospectively enroled. Left atrial voltage maps were constructed during sinus rhythm using NavX to identify LVZs (<0.5 mV), and PVAI without any LA substrate modification was performed using an open-irrigation catheter. After PVAI, 20 mg of adenosine triphosphate (ATP) was injected. Adenosine triphosphate-induced PV reconnections were eliminated by touch-up ablation when unmasked. Voltage maps revealed LVZs in 24 patients (32%) and no LVZs in 52 (68%). During 24 ± 7 months of follow-up, 15 patients (63%) with LVZs and 10 (19%) without had AF recurrences off antiarrhythmic drugs (log-rank P < 0.001). A multivariate logistic regression analysis revealed that LVZ areas [odds ratio (OR): 1.12 per 1 cm(2), 95% confidence interval (CI): 1.04-1.23, P = 0.001] and ATP-induced reconnection (OR: 2.08, 95% CI: 1.01-4.91, P = 0.046) were significant predictors of recurrence. In those with LVZs, the LVZ area was strongly correlated with the LA body volume (r = 0.81, P < 0.001) and a unique predictor of recurrence (OR: 1.17 per 1 cm(2), 95% CI: 1.01-1.55, P = 0.031), while in those without an LVZ, ATP-induced PV reconnection was a unique predictor (OR: 3.24, 95% CI: 1.15-15.39, P = 0.025).nnnCONCLUSIONnThe LVZ area was an independent predictor of recurrence after PVAI without any LA substrate modification. Adenosine triphosphate-induced PV reconnection was also an independent predictor, especially in those without LVZs.

Association Between Photoreceptor Regeneration and Visual Acuity Following Surgery for Rhegmatogenous Retinal Detachment

PURPOSEnThe purpose of this study was to evaluate foveal regeneration and the association between retinal restoration and visual acuity following reattachment surgery for rhegmatogenous retinal detachment (RRD).nnnMETHODSnTwenty-nine eyes of 29 patients with successfully reattached macula-off RRD were retrospectively analyzed. We used spectral-domain optical coherence tomography to image macular regions and measure retinal thickness and Snellen chart visual acuity (VA) to evaluate best-corrected VA (BCVA) at 1, 2, 3, 6, 9, and 12 months after vitrectomy. Best-corrected visual acuity data were converted to the logarithm of the minimum angle of resolution scale. Opposite eyes were used as controls.nnnRESULTSnThe thicknesses of the external limiting membrane (ELM)-ellipsoid zone (EZ) and EZ-retinal pigment epithelium (RPE) were significantly thinner in involved eyes than in corresponding unaffected eyes at 1 month after surgery (P < 0.001 for both), and the thickness increased over time (P < 0.001 for both). Best-corrected visual acuity significantly improved over time (P < 0.001), and the improvement correlated with EZ-RPE thickness (r = -0.45, P = 0.021). Multiple regression analysis demonstrated the presence of a foveal bulge as the independent predictor of final BCVA (P < 0.001). Eyes with a foveal bulge had significantly better BCVA and greater EZ-RPE thickness than those without throughout the follow-up period. Significant restoration of the integrity of EZ and cone interdigitation zone (CIZ) was observed over time (P < 0.001 for both) in eyes with a foveal bulge.nnnCONCLUSIONSnThe thickness of EZ-RPE and cone density increased during foveal regeneration, as demonstrated by the continuous improvements in CIZ integrity over time, leading to the formation of foveal bulge and good vision following successful reattachment of macula-off RRD.

A joint frailty-copula model between tumour progression and death for meta-analysis

Dependent censoring often arises in biomedical studies when time to tumour progression (e.g., relapse of cancer) is censored by an informative terminal event (e.g., death). For meta-analysis combining existing studies, a joint survival model between tumour progression and death has been considered under semicompeting risks, which induces dependence through the study-specific frailty. Our paper here utilizes copulas to generalize the joint frailty model by introducing additional source of dependence arising from intra-subject association between tumour progression and death. The practical value of the new model is particularly evident for meta-analyses in which only a few covariates are consistently measured across studies and hence there exist residual dependence. The covariate effects are formulated through the Cox proportional hazards model, and the baseline hazards are nonparametrically modeled on a basis of splines. The estimator is then obtained by maximizing a penalized log-likelihood function. We also show that the present methodologies are easily modified for the competing risks or recurrent event data, and are generalized to accommodate left-truncation. Simulations are performed to examine the performance of the proposed estimator. The method is applied to a meta-analysis for assessing a recently suggested biomarker CXCL12 for survival in ovarian cancer patients. We implement our proposed methods in R joint.Cox package.