Learning Curve Associated with Complications in Biportal Endoscopic Spinal Surgery: Challenges and Strategies

Study DesignDescriptions of technical strategies to overcome pitfalls associated with early learning periods in biportal endoscopic spinal surgery (BESS).PurposeTo introduce BESS for lumbar spinal diseases (LSDs) and to inform certain challenges to be overcome in mastering the technique.Overview of LiteratureBESS has shown superior benefits including excellent magnification, a wider range of view by dynamic handling of an endoscope and instruments. Clinical reports, however, have not yet been very revealing for its new introduction into minimally invasive spine surgery.MethodsTo evaluate the learning curve for BESS, the procedures for various LSDs by one surgeon were analyzed in the view of shortening of the operating times and reduction of complications. Reviewing of recorded procedures helped in finding the reasons and the implemented solutions.ResultsThe 68 cases included 25 for lumbar disc herniation (LDH), 3 for revision for recurred LDH, 39 for lumbar spinal stenosis (LSS) and 1 for synovial cyst. The operation time for the total cases averaged 83.7±33.6 minutes. According to diagnosis, it was 68.2±23.7 minutes for LDH. After the 14th case of LDH, it was nearly constant and close to the average time. One level of LSS needed 110.4±34.4 minutes. Prolonged operation times even in some later cases of LSS were mainly from struggling against blurred vision due to epidural bleeding. There were 7 cases of complications (10.3%) including 2 cases of dural tear, 1 case of root injury, and 4 cases of incomplete decompression on postoperative magnetic resonance imaging. There was no case of symptomatic hematoma or wound infection.ConclusionsBESS seemed to have a relatively short learning curve period. The overall complication rate in early learning period was 10.3%. These could be avoided by magnified regional views on an endoscope and a clear surgical field by controlling epidural bleeding

A Case of Wernicke's Encephalopathy Following Fluorouracil-based Chemotherapy

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis

Background/Aims:Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. Methods:Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). Results:The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). Conclusions:Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol

The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery.This study was supported by Johnson & Johnson. The funder has no role in study design, writing of the manuscript and the decision to submit the report for publication

Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study

BackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.Patients and methodsPatients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsOf the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.ConclusionBVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.Clinical trial registrationClinicalTrials.gov, identifier NCT02866006

Sequence-non-specific effects of RNA interference triggers and microRNA regulators

RNA reagents of diverse lengths and structures, unmodified or containing various chemical modifications are powerful tools of RNA interference and microRNA technologies. These reagents which are either delivered to cells using appropriate carriers or are expressed in cells from suitable vectors often cause unintended sequence-non-specific immune responses besides triggering intended sequence-specific silencing effects. This article reviews the present state of knowledge regarding the cellular sensors of foreign RNA, the signaling pathways these sensors mobilize and shows which specific features of the RNA reagents set the responsive systems on alert. The representative examples of toxic effects caused in the investigated cell lines and tissues by the RNAs of specific types and structures are collected and may be instructive for further studies of sequence-non-specific responses to foreign RNA in human cells

Seasonal Dependence of Aerosol Data Assimilation and Forecasting Using Satellite and Ground-Based Observations

This study examines the performance of a data assimilation and forecasting system that simultaneously assimilates satellite aerosol optical depth (AOD) and ground-based PM10 and PM2.5 observations into the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). The data assimilation case for the surface PM10 and PM2.5 concentrations exhibits a higher consistency with the observed data by showing more correlation coefficients than the no-assimilation case. The data assimilation also shows beneficial impacts on the PM10 and PM2.5 forecasts for South Korea for up to 24 h from the updated initial condition. This study also finds deficiencies in data assimilation and forecasts, as the model shows a pronounced seasonal dependence of forecasting accuracy, on which the seasonal changes in regional atmospheric circulation patterns have a significant impact. In spring, the forecast accuracy decreases due to large uncertainties in natural dust transport from the continent by north-westerlies, while the model performs reasonably well in terms of anthropogenic emission and transport in winter. When the south-westerlies prevail in summer, the forecast accuracy increases with the overall reduction in ambient concentration. The forecasts also show significant accuracy degradation as the lead time increases because of systematic model biases. A simple statistical correction that adjusts the mean and variance of the forecast outputs to resemble those in the observed distribution can maintain the forecast skill at a practically useful level for lead times of more than a day. For a categorical forecast, the skill score of the data assimilation run increased by up to 37% compared to that of the case with no assimilation, and the skill score was further improved by 10% through bias correction

Numerical Modeling for the Accidental Dispersion of Hazardous Air Pollutants in the Urban Metropolitan Area

A numerical simulation system is developed to predict the dispersion of hazardous air pollutants (HAPs) over a populated city due to accidental release. Ulsan, as one of the megacities in Korea, is chosen as an ideal testbed for the simulation, as it is located in complex terrain and hosts a national industrial complex on the outskirts of the city. The system is based on the California puff model (CALPUFF) for simulating a HAP&apos;s dispersion, in which the three-dimensional atmospheric circulation derived from the observed weather station data is specified at a fine horizontal resolution of 200 m. A test scenario is developed for the accidental release of benzene during the daytime and nighttime, respectively, by a fictitious explosion of a storage container, and the injection amount is determined arbitrarily yet comparable to those in the past accidents. In attempting a quantitative assessment and zoning the level of potential risk over the impacted area, multiple simulations have been conducted each day with different hourly varying meteorological conditions in August. The dispersion characteristics of the air pollutant depend largely on the local wind patterns that vary substantially from day to day. Nevertheless, the composite analysis sufficiently identifies the impacted area by the HAP&apos;s dispersion due to the local prevailing wind such as the land-sea breeze circulation. An immediate hazardous area is determined based on the vulnerability map constructed by zoning the level of risk determined by the spatial distribution of the HAPs&apos; concentration and the harmfulness standard to the human body