In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with ...(chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes.
Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response.
More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease.
Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UPUK
This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer.
...Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery.
Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%.
Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).
Abstract Background s: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most ...prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. Patients and methods A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. Results We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p<0.001). Conclusions We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the ...active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle.
Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350).
The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70).
Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background The purpose of this study was to evaluate the diagnostic value of dual-energy computed tomography (DECT) in detecting lymph node (LN) metastasis in patients with colorectal ...cancer. Methods Data from 81 LNs from 28 patients with colorectal adenocarcinoma were retrospectively analyzed. All patients received DECT before surgery without any neoadjuvant therapy. The diagnostic value was assessed using the iodine concentration (IC). Results In the pathological findings, 35 (43.2%) LNs from 13 patients were metastatic and 46 (56.8%) LNs from 17 patients were non-metastatic. The mean IC of metastatic LNs in the portal venous phase (PP) was 1.60 mg/ml, which was significantly lower compared with non-metastatic LNs (3.25 mg/ml, p < 0.001). Receiver operating characteristic (ROC) analysis revealed that the IC in PP had the highest ability to discriminate LN metastasis (area under the ROC curve AUC 0.932). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IC in PP (cutoff 2.1 mg/ml) were 87.0%, 88.6%, 85.3%, 90.0%, and 87.9%, respectively. When clinically obvious metastatic LNs in conventional CT findings were excluded, 50 LNs remained (5 metastatic and 45 non-metastatic LNs). In this subgroup analysis, the IC in PP remained the most powerful predictor of metastatic LNs (cutoff: 2.1 mg/ml, AUC 0.933). Conclusions The evaluation of IC in DECT may improve the diagnostic capabilities of discriminating metastatic LNs. This method may be particularly useful when conventional CT findings lead to equivocal results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Necrotising soft-tissue infections (NSTIs) of the upper limb are uncommon, but potentially life-threatening. We used a national database to investigate the risk factors for amputation of the limb and ...death. We extracted data from the Japanese Diagnosis Procedure Combination database on 116 patients (79 men and 37 women) who had a NSTI of the upper extremity between 2007 and 2010. The overall in-hospital mortality was 15.5%. Univariate analysis of in-hospital mortality showed that the significant variables were age (p = 0.015), liver dysfunction (p = 0.005), renal dysfunction (P < 0.001), altered consciousness (p = 0.049), and sepsis (p = 0.021). Logistic regression analysis showed that the factors associated with death in hospital were age over 70 years (Odds Ratio (OR) 6.6; 95% confidence interval (CI) 1.5 to 28.2; p = 0.011) and renal dysfunction (OR 15.4; 95% CI 3.8 to 62.8; p < 0.001). Univariate analysis of limb amputation showed that the significant variables were diabetes (p = 0.017) mellitus and sepsis (p = 0.001). Multivariable logistic regression analysis showed that the factors related to limb amputation were sepsis (OR 1.8; 95% CI 1.5 to 24.0; p = 0.013) and diabetes mellitus (OR 1.6; 95% CI 1.1 to 21.1; p = 0.038). For NSTIs of the upper extremity, advanced age and renal dysfunction are both associated with a higher rate of in-hospital mortality. Sepsis and diabetes mellitus are both associated with a higher rate of amputation.
ABSTRACT
Key external forcing factors have been proposed to explain the collapse of ice sheets, including atmospheric and ocean temperatures, subglacial topography, relative sea level and tidal ...amplitudes. For past ice sheets it has not hitherto been possible to separate relative sea level and tidal amplitudes from the other controls to analyse their influence on deglaciation style and rate. Here we isolate the relative sea level and tidal amplitude controls on key ice stream sectors of the last British–Irish and Fennoscandian ice sheets using published glacial isostatic adjustment models, combined with a new and previously published palaeotidal models for the NE Atlantic since the Last Glacial Maximum (22 ka BP). Relative sea level and tidal amplitude data are combined into a sea surface elevation index for each ice stream sector demonstrating that these controls were potentially important drivers of deglaciation in the western British Irish Ice Sheet ice stream sectors. In contrast, the Norwegian Channel Ice Stream was characterized by falling relative sea level and small tidal amplitudes during most of the deglaciation. As these simulations provide a basis for observational field testing we propose a means of identifying the significance of sea level and tidal amplitudes in ice sheet collapse.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The tidal regime in the Bohai Sea, China, is investigated using observations and an established numerical tidal model. The area has recently experienced rapid coastline changes due to natural ...developments of the Yellow River delta and large‐scale anthropogenic land reclamation. These morphological changes are not reflected in most global bathymetric databases and are thus rarely incorporated into investigations of the Bohai Sea. It is shown that there have indeed been significant changes in the tidal regime in the Bohai Sea over the last 35 years, with M2 amplitudes changing up to 20 cm in some parts. The model captures some of these changes when the appropriate bathymetries are used. Furthermore, the simulations show that the tides in the Bohai Sea have become more sensitive to future sea level rise and the way in which it is implemented in the model (i.e., whether or not flood defenses are included). These sensitivity changes are due to the recent coastal developments.
Key Points
Bohai Sea has undergone recent significant coastline changes
Past coastal change has lead to significant tidal changes
Tides of the Bohai Sea are sensitive to SLR
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The aim of this work was to explore whether selective muscle activation of the biceps brachii (BB) is modified by cathodal transcranial direct current stimulation (c-tDCS) in a movement ...frequency-dependent manner. Seventeen healthy participants were asked to perform repetitive isometric elbow flexion and forearm pronation at 0.75, 1.0, and 1.25 Hz, paced by an auditory metronome, before and after c-tDCS (1 mA, 15 min) applied to the primary motor cortex (M1) ipsilateral to the task side. Selectivity in the modulation of corticomotor excitability was expressed as a ratio of motor evoked potential (MEP) size in BB immediately before forearm pronation task relative to elbow flexion. Transcranial magnetic stimulation delivered to the right M1 representation of the left BB at 130% of active motor threshold either 150 or 200 ms prior to every fifth metronome beat. Cathodal tDCS over the ipsilateral M1 significantly improved MEP selectivity ratios in a frequency dependent manner primarily through selective suppression of the BB antagonist (i.e., during forearm pronation). Cathodal tDCS reduced the MEP selectivity ratio for movement-frequencies of 1.0 and 1.25 Hz but not 0.75 Hz compared to sham. Cathodal tDCS is capable of improving selective muscle activation of the ipsilateral proximal upper limb in a frequency-dependent manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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