Utilization of machine learning to accelerate colloidal synthesis and discovery.

Machine learning techniques are seeing increased usage for predicting new materials with targeted properties. However, widespread adoption of these techniques is hindered by the relatively greater experimental efforts required to test the predictions. Furthermore, because failed synthesis pathways are rarely communicated, it is difficult to find prior datasets that are sufficient for modeling. This work presents a closed-loop machine learning-based strategy for colloidal synthesis of nanoparticles, assuming no prior knowledge of the synthetic process, in order to show that synthetic discovery can be accelerated despite limited data availability.

Eosinophilic Granulomatosis with Polyangiitis Presenting as Unilateral Acute Anterior Ischaemic Optic Neuropathy.

Eosinophilic granulomatosis with polyangiitis (eGPA) is a rare vasculitis of small-medium sized vessels that can cause both anterior and posterior ischaemic optic neuropathies. Herein, the authors present a rare case of eGPA presenting initially as an acute unilateral anterior ischaemic optic neuropathy from short posterior ciliary artery vasculitis. The diagnosis presented a challenge as clinical and histopathological evidence suggested allergic rhinosinusitis, and no invasive fungal sinusitis was found. The high serum eosinophilia, asthma, optic neuropathy and paranasal sinus abnormalities fulfilled the criteria for a diagnosis of eGPA. Furthermore serum was positive for myeloperoxidase antibodies. Subsequently the case was successfully treated with oral glucocorticoids and intravenous rituximab.

Robotic versus laparoscopic hepatectomy: application of the difficulty scoring system.

BACKGROUND: The development of robotic system may help to relieve the difficulties encountered during laparoscopic hepatectomy. A difficulty scoring system (DSS) was developed to assess the difficulty of various laparoscopic liver resection procedures. The aim of this study is to explore if the DSS is applicable in robotic hepatectomy and to compare the outcomes of robotic hepatectomy and laparoscopic hepatectomy among different difficulty levels. METHODS: Clinical data from all consecutive patients who underwent robotic and conventional laparoscopic hepatectomy at the Prince of Wales Hospital, Hong Kong, were prospectively collected and reviewed. The difficulty level of operations was graded using the DSS. Perioperative outcomes of robotic and conventional laparoscopic hepatectomy were compared at each difficulty level. RESULTS: A total of 107 and 94 patients underwent robotic and laparoscopic hepatectomy during the study period, respectively. Among them, 16 and 2 patients were operated for recurrent pyogenic cholangitis, respectively, and were excluded because no mark for tumour location can be assigned. For robotic hepatectomy, a higher DSS was significantly correlated with higher minor complication rate (p = 0.001), more intraoperative blood loss (p = 0.002), longer operation time (p < 0.001) and longer post-operative hospital stay (p < 0.001). The mean DSS scores of robotic and laparoscopic hepatectomy were 4.5 and 3.6, respectively. (p = 0.004). For cases with low (DSS 1-3) and intermediate (DSS 4-6) difficulty level, there was no significant difference in operative blood loss, operation time and overall complications rate. Only 2 cases (2.2%) with high difficulty level were operated with laparoscopic approach while 20% of patients operated with robotic approach had DSS > 6. CONCLUSIONS: DSS significantly correlated with surgical outcomes in patient who underwent robotic hepatectomy. Perioperative outcomes following robotic and conventional laparoscopic hepatectomy were similar in cases with low and intermediate difficulty. However, robotic system allowed minimally invasive approach in cases with higher difficulty level.

Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial).

BACKGROUND: Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC. METHODS: Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed. RESULTS: A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001). CONCLUSIONS: MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.

The United Kingdom Neuro-Ophthalmology Superheroes Day 2019.

A key theme of the United Kingdom Neuro-ophthalmology Superheroes Day was to address emerging topics in Neuro-Ophthalmology and the meeting included speakers from around the world. Rapid cases introduced topics which included non-arteritic anterior ischaemic optic neuropathy, imaging in optic nerve disorders, paediatric optic neuritis, mitochondrial disorders and idiopathic intracranial hypertension.

Microwave ablation provides better survival than liver resection for hepatocellular carcinoma in patients with borderline liver function: application of ALBI score to patient selection.

BACKGROUND: Studies comparing microwave ablation (MWA) and liver resection are lacking. This study evaluates the survival of patients with hepatocellular carcinoma (HCC) treated with liver resection or MWA and the role of Albumin-Bilirubin (ALBI) score in patient selection for treatments. METHODS: This is a retrospective analysis of patients who received curative liver resection or MWA for HCC. Propensity score matching was used at a 1:1 ratio. The value of ALBI grade for patient selection was evaluated. Overall and disease-free survival were compared between two groups. RESULTS: Of the 442 patients underwent MWA or liver resection for HCC during the study period, 63 patients received MWA and 379 patients received liver resection. Propensity scoring matching analysis resulted in 63 matched pairs for further analysis. Subgroup analysis according to the ALBI grade was performed. Liver resection offered better overall and disease-free survivals in patients with ALBI grade 1. MWA provided a significantly better overall survival (p = 0.025) and a trend towards better disease-free survival (p = 0.39) in patients with ALBI grade 2 or 3. CONCLUSIONS: Liver resection offered superior disease-free survival to MWA in patients with HCC. The ALBI grade could identify patients with worse liver function who might gain survival advantage from MWA.

Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: A prospective cohort study.

BACKGROUND AND AIM: Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. METHODS: A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. RESULTS: A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. CONCLUSIONS: Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor.

Ligand Exchange-Mediated Activation and Stabilization of a Re-Based Olefin Metathesis Catalyst by Chlorinated Alumina.

Extensive chlorination of γ-Al2O3 results in the formation of highly Lewis acidic surface domains depleted in surface hydroxyl groups. Adsorption of methyltrioxorhenium (MTO) onto these chlorinated domains serves to activate it as a low temperature, heterogeneous olefin metathesis catalyst and confers both high activity and high stability. Characterization of the catalyst reveals that the immobilized MTO undergoes partial ligand exchange with the surface, whereby some Re sites acquire a chloride ligand from the modified alumina while donating an oxo ligand to the support. More specifically, Re LIII-edge EXAFS and DFT calculations support facile ligand exchange between MTO and Cl-Al2O3 to generate [CH3ReO2Cl+] fragments that interact with a bridging oxygen of the support via a Lewis acid-base interaction. According to IR and solid-state NMR, the methyl group remains intact, and does not evolve spontaneously to a stable methylene tautomer. Nevertheless, the chloride-promoted metathesis catalyst is far more active and productive than MTO/γ-Al2O3, easily achieving a TON of 100 000 for propene metathesis in a flow reactor at 10 °C (compared to TON < 5000 for the nonchlorinated catalyst). Increased activity is a consequence of both a larger fraction of active sites and a higher intrinsic activity for the new sites. Increased stability is tentatively attributed to a stronger interaction between MTO and chlorinated surface regions, as well as extensive depletion of the Brønsted acidic surface hydroxyl population. The reformulated catalyst represents a major advance for Re-based metathesis catalysts, whose widespread use has thus far been severely hampered by their instability.

Robotic Liver Resection For Primary Hepatolithiasis: Is It Beneficial?

BACKGROUND: Primary hepatolithiasis is a disease characterized by primary biliary ductal abnormality with stone formation predominantly within the intrahepatic bile ducts. Its management is difficult, but liver resection has emerged as a promising treatment option. METHODS: Robotic liver resection (RLR) has been adopted in our center for the management of patients with hepatolithiasis. The operative and short-term outcomes of this cohort of patients were compared with a historical cohort of patients using open approach (OLR). A subgroup analysis was performed for left lateral sectionectomy. RESULTS: Between September 2010 and April 2015, 15 RLRs were performed on patients with primary hepatolithiasis. The historical cohort consisted of 42 OLRs with operation done between January 2005 and January 2014. No differences were found in patient demographics, disease characteristics, or types of resection. No operative deaths occurred, and no difference was seen in complication rates. RLR had significantly less blood loss (100 vs. 235 ml; p = 0.011) and shorter hospital stays (6 vs. 8 days; p = 0.003). After a median follow-up of 19.4 months for RLRs and 79.2 months for OLRs (p < 0.001), there were no differences in residual stone rate, recurrent stone rate, or rate of recurrent cholangitis. Subgroup analysis of lateral sectionectomy (10 RLRs vs. 27 OLRs) revealed similar outcomes, i.e., less blood loss and shorter hospital stays in RLR. CONCLUSIONS: Robotic liver resection reduces blood loss and shortens hospital stays compared with OLR. A longer follow-up is needed to assess the long-term outcomes of RLR regarding prevention of recurrent stones and cholangitis.

The idiopathic intracranial hypertension prospective cohort study: evaluation of prognostic factors and outcomes.

BACKGROUND: There are limited longitudinal data evaluating outcomes in idiopathic intracranial hypertension (IIH). We aimed to evaluate the long-term outcomes in a real-world cohort of patients with IIH and sought to establish the prognostic factors. METHODS: A longitudinal prospective cohort study was conducted over 9 years (2012-2021). Data included demographics and disease status. All consenting patients with IIH were recruited. Visual outcomes included visual acuity, Humphrey visual field and optical coherence tomography (OCT) imaging measurements. Headache frequency, severity, and impact were noted. We analysed the key variables impacting visual and headache outcomes. RESULTS: The cohort contained 490 patients with a confirmed IIH diagnosis. 98% were female with a mean body mass index (BMI) of 38 kg/m2. Those with the highest OCT retinal nerve fibre layer had the worst visual outcomes. We noted a delayed decline, in the visual field and OCT ganglion cell layer after 12 months. In the medically managed cohort (n = 426), we found that disease duration and change in BMI had the greatest influence on visual outcomes. There was a high burden of headache, with a daily headache at presentation and prior migraine history influencing long-term headache prognosis. CONCLUSIONS: There is a delayed decline in visual outcomes in those with the most severe papilloedema. Disease duration and change in BMI were the key visual prognostic factors, therefore those with the more acute disease may require closer monitoring. Improving prognosis in IIH should focus on the potentially modifiable factor of weight management.

A laser powder bed fusion system for operando synchrotron x-ray imaging and correlative diagnostic experiments at the Stanford Synchrotron Radiation Lightsource.

Laser powder bed fusion (LPBF) is a highly dynamic multi-physics process used for the additive manufacturing (AM) of metal components. Improving process understanding and validating predictive computational models require high-fidelity diagnostics capable of capturing data in challenging environments. Synchrotron x-ray techniques play a vital role in the validation process as they are the only in situ diagnostic capable of imaging sub-surface melt pool dynamics and microstructure evolution during LPBF-AM. In this article, a laboratory scale system designed to mimic LPBF process conditions while operating at a synchrotron facility is described. The system is implemented with process accurate atmospheric conditions, including an air knife for active vapor plume removal. Significantly, the chamber also incorporates a diagnostic sensor suite that monitors emitted optical, acoustic, and electronic signals during laser processing with coincident x-ray imaging. The addition of the sensor suite enables validation of these industrially compatible single point sensors by detecting pore formation and spatter events and directly correlating the events with changes in the detected signal. Experiments in the Ti-6Al-4V alloy performed at the Stanford Synchrotron Radiation Lightsource using the system are detailed with sufficient sampling rates to probe melt pool dynamics. X-ray imaging captures melt pool dynamics at frame rates of 20 kHz with a 2 µm pixel resolution, and the coincident diagnostic sensor data are recorded at 470 kHz. This work shows that the current system enables the in situ detection of defects during the LPBF process and permits direct correlation of diagnostic signatures at the exact time of defect formation.

Management of neovascular glaucoma with transscleral cyclophotocoagulation with diode laser alone versus combination transscleral cyclophotocoagulation with diode laser and intravitreal bevacizumab.

BACKGROUND: Trans-scleral cyclophotocoagulation with diode laser has been well documented in the management of neovascular glaucoma. More recently, intravitreal bevacizumab has been increasingly employed to treat neovascular diseases of the eye. This study reports our initial experience with trans-scleral cyclophotocoagulation alone versus the combination of trans-scleral cyclophotocoagulation and intravitreal bevacizumab for management of neovascular glaucoma. DESIGN: Retrospective uncontrolled comparative case series PARTICIPANTS: A total of 31 eyes of 30 consecutive patients were included - 11 eyes in the trans-scleral cyclophotocoagulation alone group and 20 in the combination trans-scleral cyclophotocoagulation and intravitreal bevacizumab group. METHODS: The records of all patients diagnosed with neovascular glaucoma undergoing trans-scleral cyclophotocoagulation with or without intravitreal bevacizumab performed by a single ophthalmic surgeon in a glaucoma specialist centre were reviewed. MAIN OUTCOME MEASURES: Data collected included intraocular pressure, anterior segment neovascularisation, best-corrected visual acuity, use of medications and complications. RESULTS: Mean reduction in intraocular pressure was 33.5 mmHg in the trans-scleral cyclophotocoagulation group and 23.7 mmHg in the combination group, a difference of 9.8 mmHg (95% CI -1.5, 21.1). Complications included hypotony in three (27%) eyes in the trans-scleral cyclophotocoagulation group and two (10%) eyes in the combination group. Three eyes required evisceration. CONCLUSIONS: Trans-scleral cyclophotocoagulation alone is effective in lowering intraocular pressure in neovascular glaucoma. In this study, the addition of intravitreal bevacizumab to trans-scleral cyclophotocoagulation did not statistically advantage treatment outcomes.

A feasible route for the design and manufacture of customised respiratory protection through digital facial capture.

The World Health Organisation has called for a 40% increase in personal protective equipment manufacturing worldwide, recognising that frontline workers need effective protection during the COVID-19 pandemic. Current devices suffer from high fit-failure rates leaving significant proportions of users exposed to risk of viral infection. Driven by non-contact, portable, and widely available 3D scanning technologies, a workflow is presented whereby a user's face is rapidly categorised using relevant facial parameters. Device design is then directed down either a semi-customised or fully-customised route. Semi-customised designs use the extracted eye-to-chin distance to categorise users in to pre-determined size brackets established via a cohort of 200 participants encompassing 87.5% of the cohort. The user's nasal profile is approximated to a Gaussian curve to further refine the selection in to one of three subsets. Flexible silicone provides the facial interface accommodating minor mismatches between true nasal profile and the approximation, maintaining a good seal in this challenging region. Critically, users with outlying facial parameters are flagged for the fully-customised route whereby the silicone interface is mapped to 3D scan data. These two approaches allow for large scale manufacture of a limited number of design variations, currently nine through the semi-customised approach, whilst ensuring effective device fit. Furthermore, labour-intensive fully-customised designs are targeted as those users who will most greatly benefit. By encompassing both approaches, the presented workflow balances manufacturing scale-up feasibility with the diverse range of users to provide well-fitting devices as widely as possible. Novel flow visualisation on a model face is presented alongside qualitative fit-testing of prototype devices to support the workflow methodology.

Using Optical Coherence Tomography as a Surrogate of Measurements of Intracranial Pressure in Idiopathic Intracranial Hypertension.

Importance: There is an unmet need for noninvasive biomarkers of intracranial pressure (ICP), which manifests as papilledema that can be quantified by optical coherence tomography (OCT) imaging. Objective: To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP. Design, Setting, and Participants: This longitudinal cohort study used data collected from 3 randomized clinical trials that were conducted between April 1, 2014, and August 1, 2019. Participants who were female and had active idiopathic intracranial hypertension were enrolled from 5 National Health Service hospitals in the UK. Automated perimetry and OCT imaging were followed immediately by ICP measurement on the same day. Cohort 1 used continuous sitting telemetric ICP monitoring (Raumedic Neurovent P-tel device) on 1 visit. Cohort 2 was evaluated at baseline and after 3, 12, and 24 months and underwent lumbar puncture assessment of ICP. Main Outcomes and Measures: Optical coherence tomography measures of the optic nerve head and macula were correlated with ICP levels, Frisén grading, and perimetric mean deviation. The OCT protocol included peripapillary retinal nerve fiber layer, optic nerve head, and macular volume scans (Spectralis [Heidelberg Engineering]). All scans were validated for quality and resegmented manually when required. Results: A total of 104 women were recruited. Among cohort 1 (n = 15; mean [SD] age, 28.2 [9.4] years), the range of OCT protocols was evaluated, and optic nerve head central thickness was found to be most closely associated with ICP (right eye: r = 0.60; P = .02; left eye: r = 0.73; P = .002). Subsequently, findings from cohort 2 (n = 89; mean [SD] age, 31.8 [7.5] years) confirmed the correlation between central thickness and ICP longitudinally (12 and 24 months). Finally, bootstrap surrogacy analysis noted a positive association between central thickness and change in ICP at all points (eg, at 12 months, a decrease in central thickness of 50 µm was associated with a decrease in ICP of 5 cm H2O). Conclusions and Relevance: In this study, optic nerve head volume measures on OCT (particularly central thickness) reproducibly correlated with ICP and surrogacy analysis demonstrated its ability to inform ICP changes. These data suggest that OCT has the utility to not only monitor papilledema but also noninvasively prognosticate ICP levels in idiopathic intracranial hypertension.

Surface Initiated Polymer Thin Films for the Area Selective Deposition and Etching of Metal Oxides.

The area selective growth of polymers and their use as inhibiting layers for inorganic film depositions may provide a valuable self-aligned process for fabrication. Polynorbornene (PNB) thin films were grown from surface-bound initiators and show inhibitory properties against the atomic layer deposition (ALD) of ZnO and TiO2. Area selective control of the polymerization was achieved through the synthesis of initiators that incorporate surface-binding ligands, enabling their selective attachment to metal oxide features versus silicon dielectrics, which were then used to initiate surface polymerizations. The subsequent use of these films in an ALD process enabled the area selective deposition (ASD) of up to 39 nm of ZnO. In addition, polymer thickness was found to play a key role, where films that underwent longer polymerization times were more effective at inhibiting higher numbers of ALD cycles. Finally, while the ASD of a TiO2 film was not achieved despite blanket studies showing inhibition, the ALD deposition on polymer regions of a patterned film produced a different quality metal oxide and therefore altered its etch resistance. This property was exploited in the area selective etch of a metal feature. This demonstration of an area selective surface-grown polymer to enable ASD and selective etch has implications for the fabrication of both micro- and nanoscale features and surfaces.

Subsurface Cooling Rates and Microstructural Response during Laser Based Metal Additive Manufacturing.

Laser powder bed fusion (LPBF) is a method of additive manufacturing characterized by the rapid scanning of a high powered laser over a thin bed of metallic powder to create a single layer, which may then be built upon to form larger structures. Much of the melting, resolidification, and subsequent cooling take place at much higher rates and with much higher thermal gradients than in traditional metallurgical processes, with much of this occurring below the surface. We have used in situ high speed X-ray diffraction to extract subsurface cooling rates following resolidification from the melt and above the ß-transus in titanium alloy Ti-6Al-4V. We observe an inverse relationship with laser power and bulk cooling rates. The measured cooling rates are seen to correlate to the level of residual strain borne by the minority ß-Ti phase with increased strain at slower cooling rates. The α-Ti phase shows a lattice contraction which is invariant with cooling rate. We also observe a broadening of the diffraction peaks which is greater for the ß-Ti phase at slower cooling rates and a change in the relative phase fraction following LPBF. These results provide a direct measure of the subsurface thermal history and demonstrate its importance to the ultimate quality of additively manufactured materials.

Reducing vision loss in chronic eye disease.

BACKGROUND: Ocular disease in its early stages may be asymptomatic and insidious. Three of the leading causes of visual loss are cataract, age related macular degeneration and glaucoma. OBJECTIVE: This article discusses the presentation and treatment options for, and the management of, cataract, age related macular degeneration and glaucoma. DISCUSSION: Few primary prevention strategies are available as these ocular diseases are degenerative. The focus for reduction of visual loss is early detection and regular ophthalmic examination. The aim of management is to improve or maintain vision so as to preserve patient quality of life.

Dynamics of pore formation during laser powder bed fusion additive manufacturing.

Laser powder bed fusion additive manufacturing is an emerging 3D printing technique for the fabrication of advanced metal components. Widespread adoption of it and similar additive technologies is hampered by poor understanding of laser-metal interactions under such extreme thermal regimes. Here, we elucidate the mechanism of pore formation and liquid-solid interface dynamics during typical laser powder bed fusion conditions using in situ X-ray imaging and multi-physics simulations. Pores are revealed to form during changes in laser scan velocity due to the rapid formation then collapse of deep keyhole depressions in the surface which traps inert shielding gas in the solidifying metal. We develop a universal mitigation strategy which eliminates this pore formation process and improves the geometric quality of melt tracks. Our results provide insight into the physics of laser-metal interaction and demonstrate the potential for science-based approaches to improve confidence in components produced by laser powder bed fusion.

Pattern of disease recurrence and its implications for postoperative surveillance after curative hepatectomy for hepatocellular carcinoma: experience from a single center.

BACKGROUND: Hepatectomy is a widely accepted curative treatment for hepatocellular carcinoma (HCC). However, the disease frequently recurs after a curative hepatectomy. The objective of this study is to provide a better understanding of the pattern of disease recurrence and the risk factors involved so as to improve the postoperative surveillance. METHODS: A retrospective study for all patients receiving hepatectomy for HCC between 2003 and 2014 was performed. Emphasis was made on the timing and pattern of recurrent disease, and type of treatment given. RESULTS: There were 506 patients in the study. Median follow-up was 43.7 months. The 1-, 3-, 5-, 10-year overall and disease free survival were 89.5%, 74.1%, 63.9%, 49.0% and 69.5%, 54.3%, 43.4%, 30.9% respectively. Recurrent disease occurred in 267 patients, 47.2% occurred within 9 months of hepatectomy and 80.1% recurred only in liver. Median survival was shorter for recurrence occurring within 9 months compared with those occurring between 10 months and 2 years postoperatively (36.2 vs. 65.7 months, P<0.01) whilst less curative treatment was offered for patients with early (within 9 months) intrahepatic alone recurrence (22.2% vs. 51.7%, P<0.01). Multivariate analysis revealed tumor size >3.5 cm and history of rupture were risk factors for recurrence within 9 months. CONCLUSIONS: These findings suggest that recurrent diseases are common after curative hepatectomy for HCC and most recurrences occur in the remnant liver. Since almost half of recurrences occurred within first 9 months after hepatectomy, a more stringent postoperative surveillance with target imaging of liver in this period is needed. Early diagnosis of recurrent disease and curative retreatment hopefully can bring about a longer survival.