Chemotherapy-induced neurotoxicity is a significant complication in the successful treatment of many cancers. Neurotoxicity may develop as a consequence of treatment with platinum analogues ...(cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine) and more recently, thalidomide and bortezomib. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. These symptoms may be disabling, adversely affecting activities of daily living and thereby quality of life. The incidence of chemotherapy-induced neurotoxicity appears critically related to cumulative dose and infusion duration, while individual risk factors may also influence the development and severity of neurotoxicity. Differences in structural properties between chemotherapies further contribute to variations in clinical presentation. The mechanisms underlying chemotherapy-induced neurotoxicity are diverse and include damage to neuronal cell bodies in the dorsal root ganglion and axonal toxicity via transport deficits or energy failure. More recently, axonal membrane ion channel dysfunction has been identified, including studies in patients treated with oxaliplatin which have revealed alterations in axonal Na+ channels, suggesting that prophylactic pharmacological therapies aimed at modulating ion channel activity may prove useful in reducing neurotoxicity. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity will inevitably assist in the development of future neuroprotective strategies and in the design of novel chemotherapies with improved toxicity profiles.
The Thorpe scale is an energy-containing vertical overturning scale of large eddies associated with shear-generated turbulence. This study investigates indirect estimates of vertical diffusivities ...from the Thorpe scale method in the polar front region east of the Kerguelen Islands based on fine-scale density profiles gathered during the 2011 KEOPS2 (KErguelen Ocean and Plateau compared Study 2) cruise. These diffusivities are validated in comparison with diffusivities estimated from the turbulence dissipation rate directly measured via a TurboMAP (Turbulence ocean Microstructure Acquisition Profiler) microstructure profiler. The results are sensitive to the choice of the diffusivity parameterization and the overturn ratio Ro, and the optimal results have been obtained from the parameterization by Shih et al. (2005) and the Ro = 0.25 criterion, rather than the parameterization by Osborn (1980) and the Ro = 0.2 criterion originally suggested by Gargett and Garner (2008). The Thorpe-scale-derived diffusivities in the KEOPS2 region show a high degree of spatial variability, ranging from a canonical value of O(10-5) m2 s-1 in the Winter Water layer and in the area immediately north of the polar front to a high value of O(10-4) m2 s-1 in the seasonal thermocline between the surface mixed layer and the Winter Water. The latter high diffusivities are found especially over the shallow plateau southeast of the Kerguelen Islands and along the polar front that is attached to the escarpment northeast of the islands. The interaction of strong frontal flow with prominent bottom topography likely causes the observed elevated mixing rates.
Abstract Purpose This study compared the incidence of biliary complication (BC) in adult living donor liver transplant recipients who underwent right-lobe duct-to-duct anastomosis (DDA) with or ...without external biliary drainage (EBD) and intended to optimize EBD tube clamping. Methods This study consisted of a retrospective assessment of EBD effect and a prospective trial for EBD tube-clamping optimization. The retrospective study included the EBD group ( n = 208) and the non-EBD group ( n = 145). The prospective study included 60 patients with EBD. Results In the retrospective study, single DDA was performed in 83.7% of the EBD group and 80.7% of the non-EBD group ( P = .47). One-year overall incidence of BC was 14.4% in the EBD group and 16.8% in the non-EBD group ( P = .48). The incidence of early anastomotic bile leakage was 1.0% in the EBD group and 4.8% in the non-EBD group ( P = .036). In the prospective study, there was no difference in tube-clamping success rates between low- and high-output EBD groups. There was also no statistical difference between the success and failure groups in terms of graft duct size, liver function tests, and post-transplant days at tube clamping. Conclusions The size of our EBD tube was too small for the graft duct size, therefore its main role appeared to be early biliary decompression, which helped prevent bile leakage and also simplified the route of cholangiogram in detecting early BC. Hence, EBD is worthy of performing in selected patients with a high risk of anastomotic bile leak.
Laterally spreading tumors (LST) are classified into two subtypes, with the nongranular type harboring a higher risk of (pre)malignant changes than the granular type. Further subdifferentiation into ...two subgroups each has been suggested, but the clinical significance of such a subdifferentiation has not previously been studied in detail in larger numbers.
Out of 6499 patients diagnosed with colorectal adenomas between January 2006 and November 2008, 153 patients (2.35 %) had 158 LSTs, 96 with a granular and 62 with a nongranular pattern. The former group was subdivided into homogeneous and nodular mixed, the latter group into flat elevated and pseudodepressed. Clinical and histopathological parameters were compared among the four subtypes.
Parameters were variably distributed between the four groups, with nodular mixed tumors being larger than the other three types ( P < 0.0001). As in other studies, malignant transformation and premalignant lesion (HGIN/CIS) were more frequent in nodular mixed than in homogeneous tumors (45.0 % vs. 5.6 %, P < 0.001), and also more common in pseudodepressed than in flat elevated tumors (41.7 % vs. 13.2 %, P = 0.011). Submucosal invasive cancer was present in 8.3 % of nodular mixed tumors, 7.9 % of flat elevated, and 12.5 % of pseudodepressed, while it was absent in homogeneous tumors. Serrated adenoma was identified in 10.8 % of all LSTs, and sessile serrated adenoma tended to be more common in flat elevated tumors.
Further subdifferentiation of the LST lesions to identify lesions at risk of malignant transformation makes most sense in the granular type. Among nongranular LSTs, both subtypes carry a significant risk.
Abstract Background Since the establishment of the Korean Network for Organ Sharing (KONOS) in 2000, thousands of patients have been enrolled on the waiting list, but only a small proportion have ...received a deceased donor liver transplantation. This report on waiting list mortality in Korea based on data from a single institution. Methods The 1772 patients enrolled on the waiting list between February 2000 and December 2011 either have not yet received at the time of analysis or have died before receiving an organ. Survival information was obtained in February 2012 by reviewing medical records or by telephone. We excluded patients who died immediately after enrollment or after retransplantation. Results Primary diagnoses of those awaiting transplantation were hepatitis B virus-associated cirrhosis (63.7%), alcoholic liver disease (14.3%), hepatitis C virus-associated cirrhosis (13.8%), and acute liver failure due to other causes (8.1%). The priority status of patients on the waiting list was KONOS status 1 (highest priority) in 3.8%, status 2A in 3.9%, status 2B in 41.9%, status 3 to 7 (lowest priority) in 50.5%. Their median survival periods were 1, 1, 18, and 59 months, respectively. The mean Child-Pugh score was 8.5 ± 2.5 and Model for End-stage Liver Disease (MELD) score 18.1 ± 9.8. Conclusions Patients with high MELD scores or hepatocellular carcinoma succumbed soon after being entered on to the waiting list. By increasing organ donation rates and developing a risk-based allocation system, it should be possible to reduce mortality among patients on organ waiting lists.
Abstract Background A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop ...HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. Methods Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. Results Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine ( n = 5), or entecavir ( n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 106 copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. Conclusions This study suggested that various mutations in the “a” determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory.
Objectives
Neighborhood walkability has been found to be positively related to physical activity and negatively associated with risks of noncommunicable diseases. However, limited studies have ...examined its association with sarcopenia in older adults. Thus, this study aimed to examine the association between neighborhood walk score and risks of sarcopenia in a sample of older Taiwanese adults.
Design and setting
This study was a cross-sectional investigation using telephone-based survey.
Participants
A nationwide telephone-based survey targeting older adults (≥ 65 years) was conducted in Taiwan.
Measurements
Data on neighborhood walkability (determined by walk score of residential neighborhood), sarcopenia scores (measured by SARC-F), and personal characteristics were obtained. The relationships between walk score and risks of sarcopenia were examined using generalized additive models.
Results
A total of 1,056 older adults participated in the survey. In model 1 (sex and age) and model 2 (full-adjusted model), a nonlinear association between neighborhood walk score and risks of sarcopenia was observed. Results showed that risks of sarcopenia appear to be lower in neighborhoods with a 40-walk score (Car-Dependent; most errands require a car) and an 80-walk score (Very Walkable) and highest in the neighborhood with a 60-walk score (Somewhat Walkable).
Conclusions
The study revealed a nonlinear relationship between neighborhood walkability and risks of sarcopenia in older adults in Asian context. Results provided information to urban designers and public health practitioners that more walkable neighborhood may not necessarily protect older adults from risks of sarcopenia.
Aim
Anastomotic leakage is the most serious complication following low anterior resection for rectal cancer and is a major cause of postoperative morbidity and mortality. The object of the present ...study was to investigate whether rectal tube drainage can reduce anastomotic leakage after minimally invasive rectal cancer surgery.
Method
Three hundred and seventy‐four patients who underwent laparoscopic or robotic LAR for tumours located ≤ 15 cm above the anal verge between 1 April 2012 and 31 October 2014 were assessed retrospectively. Of these, 107 with intermediate risk of anastomotic leakage received transanal rectal tube drainage. The rectal tube group was matched by propensity score analysis with patients not having rectal tube drainage, giving 204 patients in the study. Covariates for propensity score analysis included age, sex, body mass index, tumour height from the anal verge and preoperative chemoradiation.
Results
Patient demographics, tumour location, preoperative chemoradiation and operative results were similar between the two groups. The overall leakage rate was 10.8% (22/204), with no significant difference between the rectal tube group (9.8%) and the nonrectal tube group (11.8%, P = 0.652). Of the patients with anastomotic leakage, major leakage requiring reoperation developed in 11.8% of those without and 3.9% of those with a rectal tube. On multivariate analysis, age over 65 years and nonuse of a rectal tube were found to be independent risk factors for major anastomotic leakage.
Conclusion
Rectal tube placement may be a safe and effective method of reducing the rate of major anastomotic leakage, alleviating the clinical course of leakage following minimally invasive rectal cancer surgery.
Abstract Background Anomalous portal vein (PV) branching in living donor livers is not uncommon and usually leads to double PV orifices of the right lobe grafts. We have assessed the long-term ...outcomes of portal Y-graft interposition for adult living donor liver transplantation (LDLT). Methods We retrospectively assessed the outcomes of 79 right-lobe LDLTs using portal Y-graft interposition among the 2001 adult LDLTs performed at our institution from January 2002 to December 2010. Results Donor PV types were type III except for one case of type II. Sources of Y-grafts were recipient autologous PV in 76 LDLTs, fresh iliac vein allografts in two, and patch plasty using recipient greater saphenous vein in one. Detailed procedures included a portal Y-graft resection with Y-limbs, corner stay sutures, tying of suture materials under direct mechanical dilatation, and direct edge-to-edge anastomosis to the recipient remnant main PV. Early PV stenting was necessary in five patients (6.3%) due to stenosis or buckling deformity. During a mean follow-up of 42 months, all PVs remained patent until patient death or censoring. Overall 1-, 3-, and 5-year patient survival rates were 93.6%, 88.3%, and 85.5%, respectively. None of the 79 donors experienced major complications requiring reoperation or therapeutic intervention. Conclusions Due to their technical feasibility and excellent long-term outcome, portal Y-graft interposition should be considered a standard procedure for reconstruction of right-lobe grafts with double PV orifices.
Circulating selenoprotein P (SeP), fibroblast growth factor (FGF) 21 and FGF23 have been associated with metabolic syndrome (MetS) in adults but not in children. We sought to evaluate the association ...among SeP, FGF21, FGF23 and MetS in young children.
A cross-sectional study conducted during a school health examination on 210 children aged 9 years. We measured serum SeP, FGF21 and FGF23 levels, and assessed anthropometric and cardiometabolic variables. MetS was defined as the presence of ⩾3 of the following five criteria: high blood pressure, low high-density lipoprotein cholesterol (HDL-C), high triglyceride, high fasting glucose and abdominal obesity.
SeP was correlated positively with HDL-C and negatively with body mass index, waist circumference (WC), blood pressure, transaminases, triglyceride and homeostasis model assessment of insulin resistance (HOMA-IR). FGF21 was directly correlated with WC, triglyceride and HOMA-IR, and FGF23 was inversely correlated with fasting glucose and alanine aminotransferase. Children with MetS had lower SeP and FGF23 levels and higher HOMA-IR than children without MetS. The highest tertile of SeP had decreased odds for MetS (odds ratio 0.05, 95% confidence interval (CI) 0.00-0.96, P for trend=0.042), whereas FGF21 and FGF23 did not relate to the risk for MetS after controlling for confounders.
Elevated SeP concentrations are independently associated with a reduced risk of MetS in children. The associations between FGF21, FGF23 and metabolic parameters are not of comparable significance.
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