Impact of chemotherapy on surgical outcomes in ileostomy reversal: a propensity score matching study from a single centre.

PURPOSE: In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications. METHODS: We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort. RESULTS: A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%, p = 1.00) and major complications (2.5% vs. 6.2%, p = 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications. CONCLUSION: Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.

Postoperative Plasmacytoid Dendritic Cells Secrete IFNα to Promote Recruitment of Myeloid-Derived Suppressor Cells and Drive Hepatocellular Carcinoma Recurrence.

Patients with hepatocellular carcinoma (HCC) confront a high incidence of tumor recurrence after curative surgical resection. Hepatic ischemia-reperfusion injury (IRI) is the major consequence of surgical stress during hepatectomy. Although it has been suggested that hepatic IRI-induced immunosuppression could contribute to tumor relapse after surgery, the underlying mechanisms have not been fully defined. Here, using a multiplex cytokine array, we found that levels of postoperative IFNα serve as an independent risk factor for tumor recurrence in 100 patients with HCC with curative hepatectomy. Plasmacytoid dendritic cells (pDC), the major source of IFNα, were activated after surgery and correlated with poor disease-free survival. Functionally, IFNα was responsible for mobilization of myeloid-derived suppressor cells (MDSC) following hepatic IRI. Conditioned medium from IFNα-treated hepatocytes mediated the migration of MDSCs in vitro. Mechanistically, IFNα upregulated IRF1 to promote hepatocyte expression of CX3CL1, which subsequently recruited CX3CR1+ monocytic MDSCs. Knockdown of Irf1 or Cx3cl1 in hepatocytes significantly inhibited the accumulation of monocytic MDSCs in vivo. Therapeutically, elimination of pDCs, IFNα, or CX3CR1 could restore the tumor-killing activity of CD8+ T cells, hence limiting tumor growth and lung metastasis following hepatic IRI. Taken together, these data suggest that IFNα-producing pDCs drive CX3CR1+ MDSC recruitment via hepatocyte IRF1/CX3CL1 signaling and lead to tumor recurrence after hepatectomy in HCC. Targeting pDCs and the IFNα/CX3CL1/CX3CR1 axis could inhibit surgical stress-induced HCC recurrence by attenuating postoperative immunosuppression. SIGNIFICANCE: IFNα secreted by plasmacytoid dendritic cells drives postoperative immunosuppression and early recurrence of hepatocellular carcinoma, providing new biomarkers and therapeutic targets to improve patient outcomes after surgical resection.

Ten-Year Experience of Chest Wall Reconstruction: Retrospective Review of a Titanium Plate MatrixRIB™ System.

Chest wall tumor resection can result in a large defect that can pose a challenge in reconstruction in restoring chest wall contour, maintaining respiratory mechanics, and improving cosmesis. Titanium plates were first introduced for treating a traumatic flail chest, which yielded promising results in restoring chest wall stability. Subsequently, the applications of titanium plates in chest wall reconstruction surgery were demonstrated in case reports and series. Our center has adopted this technique for a decade, and patients are actively followed up after operation. Here, we retrospectively analyze our 10-year experience of using titanium plates and other reconstruction approaches for chest wall reconstruction, in terms of clinical outcomes, complications, and reasons for reoperation to determine long-term safety and efficacy. Thirty-eight patients who underwent chest wall resection and reconstruction surgery were identified. Of these, 11 had titanium plate insertion, 11 had patch repair or flap reconstruction, and the remaining 16 had primary closure of defects. Chest wall reconstruction using titanium plate(s) and patch repair (with or without flap reconstruction) was associated with larger chest wall defects and more sternal resections than primary closure. Subgroup analysis also showed that reconstruction by the titanium plate technique was associated with larger chest wall defects than patch repair or flap reconstruction [286.80 cm2 vs. 140.91 cm2 (p = 0.083)]. There was no 30-day hospital mortality. Post-operative arrhythmia was more commonly seen following chest wall reconstruction compared with primary closure (p = 0.041). Furthermore, more wound infections were detected following the use of titanium plate reconstruction compared with the patch repair (with or without flap reconstruction) approach (p = 0.027). In conclusion, the titanium plate system is a safe, effective, and robust approach for chest wall reconstruction surgery, especially in tackling larger defect sizes.

Midline versus paramedian mandibulotomy for tongue cancer surgery: analysis of complications.

Midline and paramedian mandibulotomies both have distinct anatomical and surgical strengths. A retrospective study was performed at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2019 to investigate how the osteotomy site (midline (n = 221) or paramedian (n = 44)) and type (straight, notched, or stair-stepped) affect postoperative and post-radiotherapy complications in patients undergoing wide excision of tongue cancer with flap reconstruction. Midline mandibulotomies were predominantly of the straight osteotomy type, while paramedian mandibulotomies were mostly notched type (P < 0.001). Comparably low elective tooth extraction rates were found in both approaches (P = 0.556). Paramedian mandibulotomy showed a higher osteoradionecrosis rate (P = 0.026), but there was no significance in the sub-analysis of individual types. Paramedian sites were associated with more early infection (P = 0.036) and plate exposure (P = 0.036) than midline sites with the straight osteotomy type, but complication rates did not differ significantly for the notched and stair-stepped types. Paramedian sites (P = 0.020) and notched types (P = 0.006) were associated with higher odds of osteoradionecrosis in the univariable logistic regression analysis, but only the notched type remained significant in the multivariable analysis (P = 0.048). In conclusion, paramedian sites increased the rate of osteoradionecrosis, and correlation with the osteotomy type resulted in more osteoradionecrosis in notched types and more complications in straight paramedian mandibulotomies.

Compromised AMPK-PGCIα Axis Exacerbated Steatotic Graft Injury by Dysregulating Mitochondrial Homeostasis in Living Donor Liver Transplantation.

OBJECTIVE: To investigate the association of graft steatosis with long-term outcome, and to elucidate the mechanism of steatotic graft injury in adult living donor liver transplantation. SUMMARY OF BACKGROUND DATA: The utilization of steatotic graft expands the donor pool for living donor liver transplantation (LDLT). However, it remains controversial due to its high morbidity and mortality. Elucidating the mechanism of steatotic graft injury is crucial to develop therapeutic strategies targeting at graft injury and to further expand the donor pool. METHODS: Five hundred thirty patients receiving LDLT were prospectively included for risk factor analysis and outcome comparison. Rat orthotopic liver transplantation, in vitro functional experiments and mouse hepatic ischemia/ reperfusion models were established to explore the mechanisms of steatotic graft injury. RESULTS: We identified that graft with >10% steatosis was an independent risk factor for long-term graft loss after LDLT (hazard ratio 2.652, P = 0.001), and was associated with shorter cancer recurrence-free survival and acute phase liver injury. Steatotic graft displayed distinct mitochondrial dysfunction, including membrane, calcium, and energy homeostasis dysregulation. Specifically, the mitochondrial biogenesis was remarkably downregulated in steatotic graft. Inhibition of AMPK-PGC1α axis impaired mitochondrial biogenesis and was lethal to fatty hepatocyte in vitro , whereas reactivation of AMPK promoted PGC1α-mediated mitochondrial biogenesis and attenuated liver injury via restoring mitochondrial function in animal model. Conclusions: We provided a new mechanism that compromised AMPK-PGC1α axis exacerbated steatotic graft injury in LDLT by dysregulating mitochondrial homeostasis through impairment of biogenesis.

Comparison of modeling accuracy between Radixact®and CyberKnife®Synchrony®respiratory tracking system.

Synchrony Respiratory Tracking system adapted from CyberKnife has been introduced in Radixact to compensate the tumor motion caused by respiration. This study aims to compare the modeling accuracy of the Synchrony system between Radixact and CyberKnife. Two Synchrony plans based on fiducial phantoms were created for CyberKnife and Radixact, respectively. Different respiratory motion traces were used to drive a motion platform to move along the superoinferior and left-right direction. The cycle time and the amplitude of target/surrogate motion of one selected motion trace were scaled to investigate the dependence of modeling accuracy on the motion characteristic. The predicted target position, the correlation error, potential difference (Radixact only) and standard error (CyberKnife only) were extracted from raw data or log files of the two systems. The modeling accuracy was evaluated by calculating the root-mean-square (RMS) error between the predicted target positions and the input motion trace. A threshold T95 within which 95% of the potential difference or the standard error lay was defined and evaluated. Except for the motion trace with a small amplitude and a good (linear) correlation between target and surrogate motion, Radixact showed smaller RMS errors than CyberKnife. The RMS error of both systems increased with the motion amplitude and showed a decreasing trend with the increasing cycle time. No correlation was found between the RMS error and the amplitude of surrogate motion. T95 could be a good estimator of modeling accuracy for CyberKnife rather than Radixact. The correlation error defined in Radixact were largely affected by the number of fiducial markers and the setup error. In general, the modeling accuracy of the Radixact Synchrony system is better than that of the CyberKnife Synchrony system under unfavorable conditions.

Responses of midbrain auditory neurons to two different environmental sounds-A new approach on cross-sound modeling.

When modeling auditory responses to environmental sounds, results are satisfactory if both training and testing are restricted to datasets of one type of sound. To predict 'cross-sound' responses (i.e., to predict the response to one type of sound e.g., rat Eating sound, after training with another type of sound e.g., rat Drinking sound), performance is typically poor. Here we implemented a novel approach to improve such cross-sound modeling (single unit datasets were collected at the auditory midbrain of anesthetized rats). The method had two key features: (a) population responses (e.g., average of 32 units) instead of responses of individual units were analyzed; and (b) the long sound segment was first divided into short segments (single sound-bouts), their similarity was then computed over a new metric involving the response (called Stimulus Response Model map or SRM map), and finally similar sound-bouts (regardless of sound type) and their associated responses (peri-stimulus time histograms, PSTHs) were modelled. Specifically, a committee machine model (artificial neural networks with 20 stratified spectral inputs) was trained with datasets from one sound type before predicting PSTH responses to another sound type. Model performance was markedly improved up to 92%. Results also suggested the involvement of different neural mechanisms in generating the early and late responses to amplitude transients in the broad-band environmental sounds. We concluded that it is possible to perform rather satisfactory cross-sound modeling on datasets grouped together based on their similarities in terms of the new metric of SRM map.

A connection between the maximum displacements of rogue waves and the dynamics of poles in the complex plane.

Rogue waves of evolution systems are displacements which are localized in both space and time. The locations of the points of maximum displacements of the wave profiles may correlate with the trajectories of the poles of the exact solutions from the perspective of complex variables through analytic continuation. More precisely, the location of the maximum height of the rogue wave in laboratory coordinates (real space and time) is conjectured to be equal to the real part of the pole of the exact solution, if the spatial coordinate is allowed to be complex. This feature can be verified readily for the Peregrine breather (lowest order rogue wave) of the nonlinear Schrödinger equation. This connection is further demonstrated numerically here for more complicated scenarios, namely the second order rogue wave of the Boussinesq equation (for bidirectional long waves in shallow water), an asymmetric second order rogue wave for the nonlinear Schrödinger equation (as evolution system for slowly varying wave packets), and a symmetric second order rogue wave of coupled Schrödinger systems. Furthermore, the maximum displacements in physical space occur at a time instant where the trajectories of the poles in the complex plane reverse directions. This property is conjectured to hold for many other systems, and will help to determine the maximum amplitudes of rogue waves.

Haemodynamic Variations of Flow to Renal Arteries in Custom-Made and Pivot Branch Fenestrated Endografting.

OBJECTIVE: This study aimed to investigate variation of blood flow to renal arteries in custom-made and pivot branch (p-branch) fenestrated endografting, using a computational fluid dynamics (CFD) technique. METHODS: Idealised models of custom-made and p-branch fenestrated grafting were constructed on a basis of a 26 mm stent graft. The custom-made fenestration was designed with a 6 mm diameter, while the 5 mm depth renal p-branch was created with a 6 mm inner and 15 mm outer fenestration. Two configurations (option A and option B) were constructed with different locations of p-branches. Option A had both renal p-branches at the same level, whereas option B contained two staggered p-branches at lower positions. The longitudinal stent orientation in both custom-made and p-branch models was represented by a takeoff angle (ToA) between the renal stent and distal stent graft centreline, varying from 55° to 125°. Computational simulations were performed with realistic boundary conditions governing the blood flow. RESULTS: In both custom-made and p-branch fenestrated models, the flow rate and wall shear stress (WSS) were generally higher and recirculation zones were smaller when the renal stent faced caudally. In custom-made models, the highest flow rate (0.390 L/min) was detected at 70° ToA and maximum WSS on vessel segment (16.8 Pa) was attained at 55° ToA. In p-branch models, option A and option B displayed no haemodynamic differences when having the same ToA. The highest flow rate (0.378 L/min) and maximum WSS on vessel segment (16.7 Pa) were both calculated at 55° ToA. The largest and smallest recirculation zones occurred at 90° and 55° ToA respectively in both custom-made and p-branch models. Custom-made fenestrated models exhibited consistently higher flow rate and shear stress and smaller recirculation zones in renal arteries than p-branch models at the same ToA. CONCLUSIONS: Navigating the renal stents towards caudal orientation can achieve better haemodynamic outcomes in both fenestrated devices. Custom-made fenestrated stent grafts are the preferred choice for elective patients. Further clinical evidence is required to validate the computational simulations.

Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus.

Surveillance of Barrett's oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm(2) (95% CI: 0.09-4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett's and that the malignant potential of 'benign' Barrett's lesions is predetermined, with important implications for surveillance programs.

Evaluating Instantaneous Perfusion Responses of Parotid Glands to Gustatory Stimulation Using High-Temporal-Resolution Echo-Planar Diffusion-Weighted Imaging.

BACKGROUND AND PURPOSE: Parotid glands secrete and empty saliva into the oral cavity rapidly after gustatory stimulation. However, the role of the temporal resolution of DWI in investigating parotid gland function remains uncertain. Our aim was to design a high-temporal-resolution echo-planar DWI pulse sequence and to evaluate the instantaneous MR perfusion responses of the parotid glands to gustatory stimulation. MATERIALS AND METHODS: This prospective study enrolled 21 healthy volunteers (M/F = 2:1; mean age, 45.2 ± 12.9 years). All participants underwent echo-planar DWI (total scan time, 304 seconds; temporal resolution, 4 s/scan) on a 1.5T MR imaging scanner. T2WI (b = 0 s/mm2) and DWI (b = 200 s/mm2) were qualitatively assessed. Signal intensity of the parotid glands on T2WI, DWI, and ADC was quantitatively analyzed. One-way ANOVA with post hoc group comparisons with Bonferroni correction was used for statistical analysis. P < .05 was statistically significant. RESULTS: Almost perfect interobserver agreement was achieved (κ ≥ 0.656). The parotid glands had magnetic susceptibility artifacts in 14.3% (3 of 21) of volunteers during swallowing on DWI but were free from perceptible artifacts at the baseline and at the end of scans on all images. Increased ADC and reduced signal intensity of the parotid glands on T2WI and DWI occurred immediately after oral administration of lemon juice. Maximal signal change of ADC (24.8% ± 10.8%) was significantly higher than that of T2WI (-10.1% ± 5.2%, P < .001). The recovery ratio of ADC (100.71% ± 42.34%) was also significantly higher than that of T2WI (22.36% ± 15.54%, P < .001). CONCLUSIONS: Instantaneous parotid perfusion responses to gustatory stimulation can be quantified by ADC by using high-temporal-resolution echo-planar DWI.

Genetic Abnormalities in Biliary Brush Samples for Distinguishing Cholangiocarcinoma from Benign Strictures in Primary Sclerosing Cholangitis.

Background. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and is strongly associated with cholangiocarcinoma (CCA). The lack of efficient diagnostic methods for CCA is a major problem. Testing for genetic abnormalities may increase the diagnostic value of cytology. Methods. We assessed genetic abnormalities for CDKN2A, TP53, ERBB2, 20q, MYC, and chromosomes 7 and 17 and measures of genetic clonal diversity in brush samples from 29 PSC patients with benign biliary strictures and 12 patients with sporadic CCA or PSC-associated CCA. Diagnostic performance of cytology alone and in combination with genetic markers was evaluated by sensitivity, specificity, and area under the curve analysis. Results. The presence of MYC gain and CDKN2A loss as well as a higher clonal diversity was significantly associated with malignancy. MYC gain increased the sensitivity of cytology from 50% to 83%. However, the specificity decreased from 97% to 76%. The diagnostic accuracy of the best performing measures of clonal diversity was similar to the combination of cytology and MYC. Adding CDKN2A loss to the panel had no additional benefit. Conclusion. Evaluation of MYC abnormalities and measures of clonal diversity in brush cytology specimens may be of clinical value in distinguishing CCA from benign biliary strictures in PSC.

Importance of clothing removal in scalds.

OBJECTIVE: To test the hypothesis that prompt removal of clothing after scalds lessens the severity of injury. METHODS: This experimental study and case series was carried out in the Burn Centre of a tertiary hospital in Hong Kong. An experimental burn model using Allevyn (Smith & Nephew Medical Limited, Hull, England) as a skin substitute was designed to test the effect of delayed clothing removal on skin temperature using hot water and congee. Data of patients admitted with scalding by congee over a 10-year period (January 2005 to December 2014) were also studied. RESULTS: A significant reduction in the temperature of the skin model following a hot water scald was detected only if clothing was removed within the first 10 seconds of injury. With congee scalds, the temperature of the skin model progressively increased with further delay in clothing removal. During the study period, 35 patients were admitted with congee scalds to our unit via the emergency department. The majority were children. Definite conclusions supporting the importance of clothing removal could not be drawn due to our small sample size. Nonetheless, our data suggest that appropriate prehospital burn management can reduce patient morbidity. CONCLUSIONS: Prompt removal of clothing after scalding by congee may reduce post-burn morbidity.

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

OBJECTIVE: The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. METHODS: In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver operating characteristic curves and a leave-one-out analysis. RESULTS: A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain and aneusomy, were significantly associated with progression on univariate analysis. We defined an 'Abnormal Marker Count' that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI 2.6 to 29.8) increased HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). CONCLUSIONS: A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus.

Electronic Ordering System Improves Postoperative Pain Management After Total Knee or Hip Arthroplasty.

OBJECTIVES: The authors investigated the impact of computerized provider order entry (CPOE) on the delivery times of analgesia and subsequent patient outcomes. We hypothesized that patients would report less pain and use less pain medications compared with the previous paper-based system. METHODS: Two groups of patients after a total hip (THA) or knee arthroplasty (TKA) were retrospectively compared: one comprising 106 patients when the paper-based ordering system was in effect (conventional group), and one comprising 96 patients after CPOE was installed (electronic group). All patients received a regional anaesthetic at surgery (combined spinal-epidural). TKA patients also received a single-injection femoral nerve block. After transfer to the postoperative anaesthesia care unit (PACU), a patient-controlled epidural analgesia (PCEA) infusion was initiated. The following data was collected from the PACU record: time to initiation of analgesia, visual analog scale (VAS) pain scores at initiation of analgesia and hourly for the first postoperative day (POD), volume of pain medication used, length of stay (LOS) in the PACU and the hospital. RESULTS: The time to initiation of analgesia from arrival in the PACU was significantly lower in the electronic group compared to the conventional group (24.5 ± 28.3 minutes vs. 51.1 ± 26.2 minutes; mean ± SD, p < 0.001), as were VAS pain scores (0.82 ± 1.08 vs. 1.5 ± 1.52, p < 0.001) and the volume of PCEA needed to control pain (27.9 ± 20.2 ml vs. 34.8 ± 20.3 ml, p = 0.001) at 4 hours postoperatively. PACU LOS and hospital LOS did not significantly differ in the two groups. CONCLUSIONS: After implementation of CPOE, patients received their postoperative analgesia faster, had less pain, and required less medication.

EEG correlates of spatial orientation in the human retrosplenial complex.

Studies on spatial navigation reliably demonstrate that the retrosplenial complex (RSC) plays a pivotal role for allocentric spatial information processing by transforming egocentric and allocentric spatial information into the respective other spatial reference frame (SRF). While more and more imaging studies investigate the role of the RSC in spatial tasks, high temporal resolution measures such as electroencephalography (EEG) are missing. To investigate the function of the RSC in spatial navigation with high temporal resolution we used EEG to analyze spectral perturbations during navigation based on allocentric and egocentric SRF. Participants performed a path integration task in a clearly structured virtual environment providing allothetic information. Continuous EEG recordings were decomposed by independent component analysis (ICA) with subsequent source reconstruction of independent time source series using equivalent dipole modeling. Time-frequency transformation was used to investigate reference frame-specific orientation processes during navigation as compared to a control condition with identical visual input but no orientation task. Our results demonstrate that navigation based on an egocentric reference frame recruited a network including the parietal, motor, and occipital cortices with dominant perturbations in the alpha band and theta modulation in frontal cortex. Allocentric navigation was accompanied by performance-related desynchronization of the 8-13 Hz frequency band and synchronization in the 12-14 Hz band in the RSC. The results support the claim that the retrosplenial complex is central to translating egocentric spatial information into allocentric reference frames. Modulations in different frequencies with different time courses in the RSC further provide first evidence of two distinct neural processes reflecting translation of spatial information based on distinct reference frames and the computation of heading changes.

Management of secondary lymphoedema.

Lymphoedema is a chronic, progressive condition. There is no cure but it is most easily managed with early recognition and therapy; those who do not have treatment tend to worsen rapidly and advanced disease is more difficult to treat than early disease. Surgery for lymphoedema is often regarded as a last resort but traditional excisional techniques that have been slightly modified for modern practice have shown good results, whilst newer microsurgical reconstruction techniques show promise although long-term results are lacking. This report provides an update on the therapy of lymphoedema.

Prolonged sound exposure has different effects on increasing neuronal size in the auditory cortex and brainstem.

Tone at moderate levels presented to young rats at a stage (postnatal week-4) presumably that has passed the cortical critical period still can enlarge neurons in the auditory cortex. It remains unclear whether this delayed plastic change occurs only in the cortex, or reflects a change taking place in the auditory brainstem. Here we compared sound-exposure effects on neuronal size in the auditory cortex and the midbrain. Starting from postnatal day 22, young rats were exposed to a low-frequency tone (4 kHz at 65 dB SPL) for a period of 3 (postnatal day 22-25) or 7 (postnatal day 22-29) days before sacrifice. Neurons were analyzed morphometrically from 7 µm-thick histological sections. A marked increase in neuronal size (32%) was found at the cortex in the high-frequency region distant from the exposing tone. The increase in the midbrain was even larger (67%) and was found in both the low and high frequency regions. While cell enlargements were clear at day 29, only in the high frequency region of the cortex a slight enlargement was found at day 22, suggesting that the cortical and subcortical changes are synchronized, if not slightly preceded by the cortex. In contrast, no changes in neuronal size were found in the cochlear nucleus or the visual midbrain. Such differential effects of sound-exposure at the auditory centers across cortical and subcortical levels cannot be explained by a simple activity-driven change occurring earlier in the brainstem, and might involve function of other structures as for example the descending auditory system.

Double free flaps for reconstruction of complex/composite defects in head and neck surgery.

OBJECTIVE. To demonstrate the feasibility of double free flap surgery in head and neck reconstruction. DESIGN. Descriptive case series. SETTING. A university-affiliated hospital in Hong Kong. PATIENTS. Twelve patients with head and neck cancer (encountered over a 2.5-year period) who had reconstructive surgery with planned simultaneous double free flaps. RESULTS. The mean total operating time was 660 minutes and there were no flap failures. Postoperative stays ranged from 11 to 82 days; nine patients were discharged within 3 weeks and seven were able to maintain their weight with oral feeding. The survival rate up to 1 year was 64%. CONCLUSION. The use of double free flaps is an option worth considering for complex head and neck defects in carefully selected patients.

Tanshinone IIA inhibits human prostate cancer cells growth by induction of endoplasmic reticulum stress in vitro and in vivo.

BACKGROUND: Tanshinone IIA (Tan-IIA) is one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae Radix. We explored the mechanisms of cell death induced by Tan-IIA treatment in prostate cancer cells in vitro and in vivo. METHODS: Cells were treated with Tan-IIA and growth inhibition was assessed. Cell cycle profiles after Tan-IIA treatment were determined by flow cytometry. Expression levels of cell cycle regulatory proteins and apoptosis-related proteins were determined after Tan-IIA treatment. Expression levels of endoplasmic reticulum (ER) stress-regulated genes were determined to investigate their role in Tan-IIA-induced cell death. GADD153 expression was knocked down by small interfering RNA (siRNA) transfection. Rate of cell death and proliferation was obtained by 3-(4,5-dimethyl thizol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Antitumor activity of Tan-IIA was performed in LNCaP xenograft model. RESULTS: Our results showed that Tan-IIA caused prostate cancer cell death in a dose-dependent manner, and cell cycle arrest at G0/G1 phase was noted, in LNCaP cells. The G0/G1 phase arrest correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. Tan-IIA also induced ER stress in prostate cancer cells: activation and nuclear translocation of GADD153/CCAAT/enhancer-binding protein-homologous protein (CHOP) were identified, and increased expression of the downstream molecules GRP78/BiP, inositol-requiring protein-1α and GADD153/CHOP were evidenced. Blockage of GADD153/CHOP expression by siRNA reduced Tan-IIA-induced cell death in LNCaP cells. Tan-IIA also suppressed LNCaP xenograft tumor growth, causing 86.4% reduction in tumor volume after 13 days of treatment. CONCLUSIONS: Our findings suggest that Tan-IIA causes G0/G1 cell cycle arrest in LNCaP cells and its cytotoxicity is mediated at least partly by ER stress induction. These data provide evidence supporting Tan-IIA as a potential anticancer agent by inducing ER stress in prostate cancer.