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Background Endostatin and bevacizumab have been approved for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients in China; however, the clinical outcomes for each drug combined with platinum-based doublet chemotherapy (PT-DC) have not yet been directly compared. This study sought to assess the clinical outcomes of the 2 drugs combined with PT-DC in the first-line treatment of patients with advanced lung adenocarcinoma. Methods This retrospective cohort study examined the clinical data of patients with metastatic or recurrent lung adenocarcinoma (LUAD) treated with endostatin or bevacizumab combined with PT-DC as the first-line treatment from October 2010 to November 2019. Propensity score matching (PSM) was performed using a 1:1 ratio nearest neighbor algorithm. The effectiveness and safety outcomes for the 2 groups were evaluated. Results A total of 202 patients were enrolled in the study. Of these, the endostatin group comprised 124 patients and the bevacizumab group comprised 78 patients; 67 pairs of patients were identified after PSM. The progression-free survival (PFS) and overall survival (OS) of patients treated with PT-DC + endostatin and PT-DC + bevacizumab were compared [(PFS: before PSM 4.8 vs. 6.5 months, P=0.741; after PSM 6.5 vs. 6.1 months, P=0.402), (OS: before PSM 21.1 vs. 39.3 months, P=0.912; after PSM 23.6 vs. 39.3 months, P=0.579)]. The objective response rates (ORRs) and disease control rates (DCRs) of the 2 groups were comparable (37.7% vs. 50.7%, P=0.094; 89.6% vs. 92.5%, P=0.545). Adverse events (AEs) ≥ grade 3 were not observed in the PT-DC + endostatin group. Three (3.8%) cases of AEs ≥ grade 3 were observed the PT-DC + bevacizumab group, comprising hypertension (n=1), proteinuria (n=1), hemoptysis (n=1). Conclusions This retrospective analysis showed that in first-line treatments, PT-DC + endostatin and PT-DC + bevacizumab appear to produce similar anti-tumor activities in patients with metastatic or recurrent lung adenocarcinoma. PT-DC + bevacizumab tended to result in worse adverse reactions than PT-DC + endostatin.

Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Background Small cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large‐scale real‐world analysis is lacking. Methods Patients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan–Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors. Results Among 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS‐SCLC) and extensive stage small cell lung cancer (ES‐SCLC), separately. Limited‐stage, good performance status (PS) (ECOG 0–1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first‐line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS‐SCLC; while good PS (ECOG 0–1), without liver, bone, or subcutaneous metastases, response to first‐line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES‐SCLC. Conclusions The present study retrieved from large real–world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively., The present study of real‐world data from 988 patients suggested that elevating primary systemic therapy response rate and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively.

Aims Alcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis. Methods We performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase. Results Among 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST > 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells. Conclusion Abnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.

Oxidative stress is considered a possible mechanism of irritable bowel syndrome (IBS) and depression. This study determined the possible association of serum peroxiredoxin 1 (PRDX1; a key antioxidant enzyme) and brain-derived neurotrophic factor (BDNF) with anxiety and depression symptoms in IBS patients.According to the Rome IV diagnostic criteria, 177 IBS patients from February 2019 to July 2019 were included. Serum levels of PRDX1, BDNF, and TNFα were detected by enzyme-linked immunosorbent assay. Levels of anxiety and depression were assessed with the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS).Compared with normal IBS patients, patients with anxiety and depression symptoms had significantly higher serum PRDX1 (p0.001; p=0.002) and TNFα (p0.001; p = 0.002) and significantly lower BDNF (p 0.001; p = 0.002). Serum PRDX1 (r = 0.659, p 0.001; r = 0.466, p 0.001) and TNFα (r = 0.531, p 0.001; r = 0.449, p 0.001) were positively correlated with SAS and SDS, respectively, whereas BDNF was negatively correlated with SAS (r = 0.594, p 0.001) and SDS (r = 0.534, p 0.001). Multivariable regression analysis revealed that IBS severity, BDNF, and PRDX1 were significant predictors of anxiety. BDNF was also a significant predictor of depression.Elevated PRDX1 and decreased BDNF in serum may be closely related to psychological symptoms in IBS. Results of this study suggested that PRDX1 may be an important target for IBS treatment in fighting against intestinal and psychological symptoms.

Objectives To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs). Methods Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated. Key findings In the genotype–toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3–4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes. Conclusions The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.

The purpose of this prospective phase II clinical trial was to investigate the efficacy and safety of anlotinib in patients with relapsed small cell lung cancer (SCLC). Forty‐five patients with relapsed SCLC were enrolled and treated with anlotinib (one cycle of 12 mg daily for 14 days, discontinued for 7 days, and repeated every 21 days) until disease progression or intolerance of treatment. The primary end point was progression‐free survival (PFS). Secondary end points were overall survival (OS), disease control rate (DCR), objective control rate (ORR) and toxicity. The median PFS was 4.1 months (95% confidence interval [CI] 2.4‐5.8) and the median OS was 6.1 months (95% CI 2.2‐10.0). The OS for the limited‐stage subgroup was significantly longer than that of the extensive‐stage subgroup (P = .02). The DCR was 67%, and the ORR was 11%. The most common adverse event was hypertension (13%), which was controlled well with antihypertensive drugs. In conclusion, anlotinib has likely efficacy in patients with relapsed SCLC, and the side effects can be well tolerated. A longer OS was observed in limited‐stage SCLC patients treated with anlotinib., What's new? Although untreated small cell lung cancer (SCLC) patients are usually sensitive to chemotherapy, they are prone to relapse. Anlotinib is a novel multi‐target small molecule tyrosine kinase inhibitor with both anti‐angiogenesis and anti‐tumor growth effects. While anlotinib became the first drug approved for third‐line and further‐line treatment of SCLC in China, few studies have focused on anlotinib treatment in relapsed SCLC. This one‐arm, prospective phase II clinical study reports a median progression‐free survival of 4.1 months (95% CI 2.4‐5.8) and median overall survival of 6.1 months (95% CI 2.2‐10.0) for anlotinib treatment in relapsed SCLC, with relatively mild side effects.

Alcohol-associated liver disease (ALD) represents a spectrum of histopathological changes, including alcoholic steatosis, steatohepatitis, and cirrhosis. One of the early responses to excessive alcohol consumption is lipid accumulation in the hepatocytes. Lipid ω-hydroxylation of medium- and long-chain fatty acid metabolized by the cytochrome P450 4A (CYP4A) family is an alternative pathway for fatty acid metabolism. The molecular mechanisms of CYP4A in ALD pathogenesis have not been elucidated. In this study, WT and Shp-/- mice were fed with a modified ethanol-binge, National Institute on Alcohol Abuse and Alcoholism model (10 days of ethanol feeding plus single binge). Liver tissues were collected every 6 hours for 24 hours and analyzed using RNA-Seq. The effects of REV-ERBα agonist (SR9009, 100 mg/kg/d) or CYP4A antagonist (HET0016, 5 mg/kg/d) in ethanol-fed mice were also evaluated. We found that hepatic Cyp4a10 and Cyp4a14 expression were significantly upregulated in WT mice, but not in Shp-/- mice, fed with ethanol. ChIP quantitative PCR and promoter assay revealed that REV-ERBα is the transcriptional repressor of Cyp4a10 and Cyp4a14. Rev-Erbα-/- hepatocytes had a marked induction of both Cyp4a genes and lipid accumulation. REV-ERBα agonist SR9009 or CYP4A antagonist HET0016 attenuated Cyp4a induction by ethanol and prevented alcohol-induced steatosis. Here, we have identified a role for the SHP/REV-ERBα/CYP4A axis in the pathogenesis of ALD. Our data also suggest REV-ERBα or CYP4A as the potential therapeutic targets for ALD.

Alcohol-associated liver disease (ALD) is a consequence of excessive alcohol use. It comprises a spectrum of histopathologic changes ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma. The public health impact of ALD is growing because of an increase in the prevalence and incidence of ALD in parallel with liver transplant and mortalities. There are multiple factors involved in the pathogenesis and progression of ALD. Reducing alcohol consumption is the cornerstone of ALD management. The efforts to reduce excessive alcohol use at the individual and population levels are urgently needed to prevent adverse outcomes from ALD.

Background Pulmonary sarcomatoid carcinoma (PSC) is a rare and poorly differentiated type of non-small cell lung cancer (NSCLC) with specific characteristics, which usually presents a challenge in clinical practice. Mesenchymal-epithelial transition (MET) gene has been identified as a promising target for treatments in the past few years. Here, we report a case of a patient with PSC harboring MET exon 14 mutation, who responded to a novel MET inhibitor - savolitinib. Case presentation A 75-year-old male patient with symptoms of cough, dyspnea and intermittent chest pain was diagnosed with sarcomatoid carcinoma. The tumor involved the right lung, the right hilum and multiple lesions in the right pleura, indicating a clinical disease stage IV. Next-generation sequencing of lung biopsy specimen indicated a MET exon 14 skipping mutation (NM_000245:c.3028+3A>G), with a variant allele frequency of 73.9%. The patient achieved a rapid and durable partial response with the initiation of savolitinib administration (600 mg, orally, once daily). The progression-free survival in this patient was 36 weeks. There were no ≥grade 3 adverse events reported and there was no dose reduction during treatment. Following savolitinib treatment, the allele frequency of MET exon 14 mutation in plasma circulating tumor DNA decreased with the reduction in tumor size. At the time of disease progression, fibroblast growth factor receptor 1 (FGFR1), EGFR and KRAS gene amplification were newly identified in tumor biopsy sample. Conclusion This patient with PSC harboring MET exon 14 skipping mutation achieved significant clinical benefit with savolitinib treatment. Emergence of FGFR1, EGFR and KRAS gene amplification at the time of disease progression was likely responsible for the resistance to savolitinib in this case.

Background This real‐world study assessed the efficacy and toxicity of anlotinib as salvage treatment in Chinese patients with advanced non‐small cell lung cancer (NSCLC). Methods The medical records of 81 patients with advanced NSCLC who had failed at least two lines of chemotherapy were retrospectively collected. All patients were administered anlotinib treatment until disease progression or intolerance as a result of adverse events. Survival curves were created using the Kaplan–Meier method. The log‐rank test was used for univariate analysis of progression‐free survival (PFS) between groups. Cox regression was used to estimate the statistically significant factors based on univariate analysis. Results The median PFS was five months (95% confidence interval [CI] 3.5–6.5). The objective response rate (ORR) was 7% and the disease control rate (DCR) was 84%. The following subgroups of patients had longer PFS (P

BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.

Complications following pediatric cranioplasty after craniectomy with either autologous bone flaps or cranial implants are reported to be common, particularly bone flap resorption. However, only sparse data are available regarding cranioplasty strategies, complications, and outcomes. This manuscript describes a Canadian-Dutch multicenter pediatric cohort study with autografts and cranial implant cranioplasties following craniectomies for a variety of indications. The study included all children (

Background Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first-line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti-angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma. Methods The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first-line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed. Results Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression-free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups. Conclusions GP has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS.

BackgroundProgrammed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors are increasingly used in China, but no real-world data are available about the immune-related adverse events (irAEs). This real-world retrospective study aimed to assess the safety and effectiveness of PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC) and to analyze the association between irAEs and effectiveness.MethodsThis was a retrospective study of the clinical data of patients with NSCLC treated with PD-1/PD-L1 inhibitors from August 2016 to November 2019 at Beijing Cancer Hospital. The patients were divided into the irAE or non-irAE groups. Overall adverse events, the impact of irAE on tumor response, and the association of irAEs with effectiveness were evaluated.ResultsOne hundred and ninety-one patients were included, including 70 (36.6%) patients in the irAE group and 121 (63.4%) patients in the non-irAE group. AE, grades 3–5 AEs, and irAE occurred in 107 (56.0%), 24 (12.6%), and 70 (36.6%) of the patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were higher in the irAE group compared with the non-irAE group (42.0% vs. 25.8%, P=0.038; 91.9% vs. 70.8%, P=0.002). Multivariable analyses identified that irAE were associated with progression-free survival (HR=0.62, 95%CI: 0.43–0.91; P=0.015), but not with overall survival (HR=0.76, 95%CI: 0.44–1.28; P=0.299).ConclusionIn NSCLC treated with PD-1/PD-L1 inhibitors, patients with irAEs showed improved effectiveness over patients without irAEs. Future studies of anti-PD-1/PD-L1 immunotherapy should explore this association and the underlying biological mechanisms of efficacy.

Background Intermediate nerve neuralgia (INN) is a rare and often overlooked form of primary otalgia. The pathophysiological mechanism is unknown, although one of the possible contributing factors is a neurovascular conflict at the root entry zone of the intermediate nerve. The pain can be severely debilitating, and the palette of treatment options is small. Objective To assess the outcome of microvascular decompression (MVD) of the VII/VIII cranial nerve complex for treating INN. Methods We retrospectively reviewed the records of a group of 8 consecutive patients with INN who underwent MVD of the VII/VIII cranial nerve complex in the period 1994 to 2015. Results In total, 7 of the 8 patients experienced almost immediate and complete relief of pain, which remained at long-term follow-up (mean 35 mo ± 24 mo, range 8-84 mo). Postoperatively, 1 patient had a cerebrospinal fluid (CSF) leak, 3 patients experienced permanent ipsilateral hearing loss, and 3 patients had temporary complaints associated with excessive drainage of CSF. Conclusion This study suggests MVD as a valid treatment for medically refractory INN. MVD carries surgical risk, but given the severity of complaints of these patients, we believe the treatment benefits outweigh the associated complications.

BACKGROUND Low-grade inflammation occurs in some patients with irritable bowel syndrome (IBS). However, the exact inflammatory markers of IBS and the relationship of these markers with IBS subtypes and symptoms are poorly defined. Peroxiredoxin 1 (PRDX1) plays an important role in inflammatory responses, including intestinal inflammation. We investigated whether PRDX1 is associated with the diagnosis, subtypes, and symptom severity of IBS. METHODS A total of 177 IBS patients and 174 sex- and age-matched healthy controls (HCs) were recruited. The PRDX1 levels in the sera and colonic mucosa of the participants were detected by enzyme-linked immunosorbent assays and immunohistochemistry. The severity of IBS symptoms was assessed using the IBS Severity Scoring System (SSS) questionnaire. RESULTS The PRDX1 levels in the sera (F = 71.81, P

Background Childhood Brain Tumor Survivors (CBTS) are at increased risk of hypothalamic-pituitary (HP) dysfunction, which may be caused by radiotherapy , be a complication of the tumor itself or due to brain injury. Being overweighted or underweighted (body mass index (BMI) more than 2 SDS or lower than -2 SDS, respectively) at brain tumor diagnosis may reflect early hypothalamic dysfunction and may be a risk factor to develop HP dysfunction during follow-up. This has, to date, not been investigated. The objective of this study was to examine whether BMI at brain tumor diagnosis is associated with the development of HP dysfunction, independent of brain tumor treatment. Methods Children surviving a brain tumor, excluding craniopharyngioma or a pituitary tumor, for minimally two years, in whom BMI at diagnosis of their brain tumor had been recorded were included from a previous cohort study (n=685 of 718). Odds-ratios (OR) for developing HP dysfunction were calculated using multivariable logistic regression, including BMI at diagnosis, gender, age at follow-up, radiotherapy, histology, location of the primary tumor, hydrocephalus and state of disease. Results Of all, 10.8% (n=74) was overweighted and 5.0% (n=34) was underweighted at diagnosis. Median follow-up time was 7.1 years (5.0-9.6). Being overweighted or underweighted at diagnosis was significantly associated with the development of HP dysfunction (anterior or posterior pituitary deficiency or central precocious puberty , OR 2.43, 95% CI 1.46-4.05) and obesity at follow-up (OR 3.75, 95% CI 2.36-5.97).Development of HP dysfunction was also significantly associated with radiotherapy (OR 11.25, 95% CI 6.76-18.72) and location of primary tumor (OR 2.24, 95% CI 1.60-3.13). In children not treated with radiotherapy (n=430), underweight and overweight at brain tumor diagnosis were also both significantly associated with HP dysfunction and precocious puberty (OR 2.91, 95% CI 1.16-7.28 and 3.00 , 95% CI 1.12-8.01, respectively). In this group, other significant risk factors for HP dysfunction included location of primary tumor (OR 8.90, 95% CI 4.11-19.24), hydrocephalus (2.27, 95% CI 1.06-4.88) and state of disease at follow-up (OR 6.38, 95% CI 1.37-29.58). Conclusions Being overweighted or underweighted at brain tumor diagnosis in childhood is associated with the development of anterior pituitary deficiencies, posterior pituitary deficiencies and CPP, independently of given treatment. This suggests that in these children hypothalamic dysfunction may already be present at brain tumor diagnosis. These findings may be used for future studies on hypothalamic dysfunction in CBTS and can be used to develop recommendations on monitoring the development of pituitary disorders in CBTS.

Objective The incidence of cranial radiotherapy (cRT)–induced central hypothyroidism (TSHD) in childhood brain tumor survivors (CBTS) is reported to be low. However, TSHD may be more frequent than currently suspected, as its diagnosis is challenging due to broad reference ranges for free thyroxine (FT4) concentrations. TSHD is more likely to be present when FT4 levels progressively decline over time. Therefore, we determined the incidence and latency time of TSHD and changes of FT4 levels over time in irradiated CBTS. Design Nationwide, 10-year retrospective study of irradiated CBTS. Methods TSHD was defined as ‘diagnosed’ when FT4 concentrations were below the reference range with low, normal or mildly elevated thyrotropin levels, and as ‘presumed’ when FT4 declined ≥ 20% within the reference range. Longitudinal FT4 concentrations over time were determined in growth hormone deficient (GHD) CBTS with and without diagnosed TSHD from cRT to last follow-up (paired t-test). Results Of 207 included CBTS, the 5-year cumulative incidence of diagnosed TSHD was 20.3%, which occurred in 50% (25/50) of CBTS with GHD by 3.4 years (range, 0.9–9.7) after cRT. Presumed TSHD was present in 20 additional CBTS. The median FT4 decline in GH-deficient CBTS was 41.3% (P P = 0.02) in GH-deficient CBTS without diagnosed TSHD. Conclusions FT4 concentrations in CBTS significantly decline over time after cRT, also in those not diagnosed with TSHD, suggesting that TSHD occurs more frequently and earlier than currently reported. The clinical relevance of cRT-induced FT4 decline over time should be investigated in future studies.

Complications following cranioplasty with either autografts or cranial implants are commonly reported in pediatric patients. However, data regarding cranioplasty strategies, complications and long-term outcomes are not well described. This study systematically reviews the literature for an overview of current cranioplasty practice in children. A systematic review of articles published from inception to July 2018 was performed. Studies were included if they reported the specific use of cranioplasty materials following craniectomy in patients younger than 18 years of age, and had a minimum follow-up of at least 1 year. Twenty-four manuscripts, describing a total of 864 cranioplasty procedures, met the inclusion criteria. The age of patients in this aggregate ranged from 1 month to 20 years and the weighted average was 8.0 years. The follow-up ranged from 0.4 months to 18 years and had a weighted average of 40.4 months. Autologous bone grafts were used in 484 cases (56.0%). Resorption, infection and/or hydrocephalus were the most frequently mentioned complications. In this aggregate group, 61 patients needed a revision cranioplasty. However, in 6/13 (46%) papers studying autologous cranioplasties, no data was provided on resorption, infection and revision cranioplasty rates. Cranial implants were used in 380 cases (44.0%), with custom-made porous hydroxyapatite being the most commonly used material (100/380, 26.3%). Infection and migration/fracturing/loosening were the most frequently documented complications. Eleven revision cranioplasties were reported. Again, no data was reported on infection and revision cranioplasty rates, in 7/16 (44%) and 9/16 (56%) of papers, respectively. Our systematic review illuminates that whether autografts or cranial implants are used, postcranioplasty complications are quite common. Beyond this, the existing literature does not contain well documented and comparable outcome parameters, suggesting that prospective, long-term multicenter cohort studies are needed to be able to optimize cranioplasty strategies in children who will undergo cranioplasty following craniectomy.

Background: Training in Bayesian reasoning may have limited impact on accuracy of probability estimates. In this study, our goal was to explore whether residents previously exposed to Bayesian reasoning use heuristics rather than Bayesian reasoning to estimate disease probabilities. We predicted that if residents use heuristics then post-test probability estimates would be increased by non-discriminating clinical features or a high anchor for a target condition.Method: We randomized 55 Internal Medicine residents to different versions of four clinical vignettes and asked them to estimate probabilities of target conditions. We manipulated the clinical data for each vignette to be consistent with either 1) using a representative heuristic, by adding non-discriminating prototypical clinical features of the target condition, or 2) using anchoring with adjustment heuristic, by providing a high or low anchor for the target condition.Results: When presented with additional non-discriminating data the odds of diagnosing the target condition were increased (odds ratio (OR) 2.83, 95% confidence interval [1.30, 6.15], p = 0.009). Similarly, the odds of diagnosing the target condition were increased when a high anchor preceded the vignette (OR 2.04, [1.09, 3.81], p = 0.025).Conclusions: Our findings suggest that despite previous exposure to the use of Bayesian reasoning, residents use heuristics, such as the representative heuristic and anchoring with adjustment, to estimate probabilities. Potential reasons for attribute substitution include the relative cognitive ease of heuristics vs. Bayesian reasoning or perhaps residents in their clinical practice use gist traces rather than precise probability estimates when diagnosing.

ObjectiveTo compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an “early approach” (EA), based on ventricular measurements exceeding normal (ventricular index [VI] MethodsObservational cohort study of 127 preterm infants (gestation ResultsForty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>−1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores ConclusionIn preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks.Classification of evidenceThis study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.

AIM Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who experienced progression with two or more lines chemotherapy have no treatment options that clearly confer a survival benefit. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain antitumor effect for various solid tumors. The present study evaluated the efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage treatment in Chinese real-world practice. METHODS Twenty-eight patients were enrolled in this observational study from October 2015 to May 2017. Progression-free survival (PFS) and overall survival (OS) were graphed by Kaplan-Meier curve and intergroup comparisons were carried out by log-rank test. Objective response rate (ORR), disease control rate (DCR) and adverse effects (AEs) were also evaluated. RESULTS Seven patients obtained partial response, and 18 obtained stable disease, representing an ORR of 26% and a DCR of 93%. Median PFS and OS were 3 (95% confidence interval [CI] 2.6-3.4) and 7.4 (95% CI 1.3-13.5) months, respectively. The efficacy analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status 0-1 was correlated with prolonged OS and PFS (P

Background Fronto-supraorbital bar advancement in the treatment for trigonocephaly is associated with extensive intraoperative blood loss and compensatory erythrocyte transfusions. Since both are related to the length of surgery, efforts have been focused on optimizing preoperative preparations. The utilization of three-dimensional skull models in surgical planning allows for familiarization with the patient's anatomy, the optimization of osteotomies, the preparation of bone grafts and the selection of fixation plates. Methods Stereolithographic skull models were used in the surgical planning for five patients with non-syndromic trigonocephaly treated in Wilhelmina Children's Hospital in 2012. A comparison group was composed of six patients with non-syndromic trigonocephaly treated by the same surgical team. Once all patients had received surgery, a retrospective chart review was performed to identify the volumes of perioperative blood loss and erythrocyte transfusions and the length of the procedure. Furthermore, the educational value of the models was assessed in a round table discussion with the surgical team and residents. Results In the model group patients were transfused a mean 24 ml/kg (27% of Estimated Blood Volume [EBV]) compared to 16 ml/kg (18% of EBV) in the comparison group ( P = 0.359) for a mean perioperative blood loss of 53 ml/kg (60% of EBV) in the model group against 40 ml/kg (41% of EBV) in the comparison group ( P = 0.792). The mean length of surgery in the model groups was 256 min versus 252 min in the comparison group ( P = 0.995). Evaluation of educational purposes demonstrated that the models had a role in the instruction of residents and communication to parents, but did not improve the insight of experienced surgeons. Conclusion The usage of stereolithographic skull models in the treatment of non-syndromic trigonocephaly does not reduce the mean volume of perioperative erythrocyte transfusions, the mean volume of perioperative blood loss nor the mean length of the surgical procedure. Nonetheless, the models do facilitate the education of the patient's parents as well as support the training of residents.

Background The role of surgery in limited small cell lung cancer (SCLC) is still controversial. To assess the role of surgery in SCLC we performed a retrospective analysis of survival in a group of limited stage patients, who were managed with trimodal therapy including surgery, or with chemotherapy and radiotherapy. Methods We performed a retrospective survival analysis in a series of 153 limited stage SCLC patients treated between 1995 and 2013. Kaplan-Meier survival analysis and Cox regression analysis were used to calculate the overall survival of the surgical and non-surgical groups. Results Median survival in all patients was 21.5 months. Median survival for surgical and non-surgical patients was 30.5 months and 16.9 months, respectively. The survival curves for the two arms are significantly different (P < 0.01). In multivariate analysis, the benefit of surgical treatment and thoracic radiotherapy varied in a time-dependent fashion. Conclusions Our results suggest that surgery added to chemotherapy and radiotherapy may be associated with a therapeutic benefit in limited SCLC.

RESULTS: In MISC, the median duration of surgery (90 versus 178 min.), anesthesia time (178 versus 291 min), and intubation time (153 versus 294 min) were all significantly (P CONCLUSIONS: Minimally invasive strip craniectomy simplifies anesthesia practice relative to OESC with shorter operative times, decreased needs for replacement fluids and blood products, lessened requirements for invasive monitoring, and reduced demands for postoperative high care beds.OBJECTIVES: The aim of the study was, first, to compare the anesthesia practice in MISC and open extended strip craniectomy (OESC), and, second, to evaluate the incidence of perioperative complications in both surgical procedures.BACKGROUND: Traditional open corrective surgery for isolated sagittal synostosis entails significant blood loss, transfusion rates, morbidity, and a lengthy hospitalization. Minimally invasive strip craniectomy (MISC) was introduced to avoid the disadvantages of open techniques.METHODS: A retrospective analysis was conducted for all consecutive patients receiving either OESC or MISC for nonsyndromic isolated sagittal synostosis between January 2006 and February 2014. The primary endpoints were the volume of blood loss, the volume of infused blood products, the duration of surgery, the anesthesia time, the intubation time, and the length of admission to high care units and the hospital.

Objective: To describe our experience with a cohort of 295 infants with progressive ventricular dilatation occurring in the antenatal or neonatal period.Methods: A search was performed in our cranial ultrasound database. All records and images of infants in whom an imaging diagnosis of progressive ventricular dilatation had been made were retrieved. In addition, modes of treatment were analysed.Results: Between February 1991 and March 2012, 295 neonates were admitted to our level 3 neonatal intensive care unit (NICU), and developed progressive ventricular dilatation for which they required intervention. In the majority of these infants, progressive ventricular dilatation developed following IVH grade III or IV (240/295; 81%) of whom 214/240 (89%) were preterms. Temporary treatment with lumbar punctures and punctures from ventricular reservoirs was sufficient for the majority of the preterms. A ventricular reservoir was inserted in 216/295 infants (73%). The overall infection rate was low (6%). A ventriculoperitoneal shunt (VP shunt) was inserted in 32% of the whole cohort, revision within 3 months was necessary in 20%, and shunt-related infection occurred in 12%.Conclusions: This large, single-centre cohort study reports the management of progressive ventricular dilatation in newborn infants. We have shown that with our approach, complications stay within acceptable limits.

The aim of this study was to investigate the efficacy and safety of the extended use of platinum-based doublet chemotherapy (PT-DC) plus endostatin in patients with advanced nonsmall cell lung cancer (NSCLC). We performed a retrospective analysis of 200 newly diagnosed advanced NSCLC patients who had received at least 1 cycle of endostatin plus PT-DC between September 2009 and November 2014. Of these patients, 155 received 4 or more cycles of therapy (the extended therapy group), while 45 received less than 4 cycles of therapy (the control group). Clinical tumor responses, progression-free survival (PFS), overall survival (OS), and toxicity profiles were recorded and retrospectively analyzed. In the extended therapy group, 67 patients (43.2%) achieved a best overall response rate of partial response (PR), while in the control group, 13 patients (28.9%) had a best overall response rate of PR. After a median follow-up of 15.9 months, the median PFS and OS were 8.0 and 23.1 months in the extended arm and 5.8 and 14.0 months in the control arm, respectively. There were statistically significant differences in median PFS and OS between these 2 arms. Hematologic and gastrointestinal toxicities occurred more frequently in the extended therapy group, but no statistically significant difference was detected in grade 3 to 4 toxicities overall between these 2 groups. In conclusion, extended treatment using endostatin combined with PT-DC can provide additional survival benefits and satisfactory toxicity profiles in previously untreated patients with NSCLC, which merits further evaluation in a larger prospective study.

Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients with craniopharyngeoma or a pituitary gland tumor were excluded. Results of all endocrine investigations, which were performed at diagnosis and during follow-up, were collected from patient charts. Multivariable logistic regression was used to study associations between demographic and tumor- and treatment-related variables and the prevalence of early endocrine disorders. Results After a median follow-up of 6.6 years, 178 CBTS (24.8%) were diagnosed with an endocrine disorder. A total of 159 CBTS (22.1%) presented with at least one endocrine disorder within the first 5 years after diagnosis. The most common endocrine disorders were growth hormone deficiency (12.5%), precocious puberty (12.2%), thyroid-stimulating hormone deficiency (9.2%), and thyroidal hypothyroidism (5.8%). The risk of hypothalamic-pituitary dysfunction (n = 138) was associated with radiotherapy (odds ratio [OR], 15.74; 95% CI, 8.72 to 28.42), younger age at diagnosis (OR, 1.09; 95% CI, 1.04 to 1.14), advanced follow-up time (OR, 1.10; 95% CI, 1.02 to 1.18), hydrocephalus at diagnosis (OR, 1.77; 95% CI, 1.09 to 2.88), and suprasellar (OR, 34.18; 95% CI, 14.74 to 79.29) and infratentorial (OR, 2.65; 95% CI, 1.48 to 4.74) tumor site. Conclusion The prevalence of early endocrine disorders among CBTS is high. The observation that 22.1% of CBTS developed at least one endocrine disorder within the first 5 years after diagnosis stresses the importance of early and regular assessment of endocrine function in CBTS who are at risk for endocrine damage.

OBJECTIVE: To evaluate the differential impact of germinal matrix-intraventricular hemorrhage (GMH-IVH) and posthemorrhagic ventricular dilatation (PHVD) on brain and cerebrospinal fluid (CSF) volumes and diffusion variables in preterm born infants at term-equivalent age (TEA). STUDY DESIGN: Nineteen infants (gestational age

Raised intracranial pressure (ICP) in infants with hydrocephalus may cause (ir)reversible damage to the brain parenchyma but can be present without clinical signs and/or symptoms. Therefore, new, favorably noninvasive, detection methods are needed to distinguish between compensated hydrocephalus with normal intracranial pressure and slowly progressive hydrocephalus with increased intracranial pressure. Because early ischemic changes in the brain parenchyma are associated with increased intracranial pressure, transcranial Doppler (TCD) indices may be useful to detect increased intracranial pressure in infants with hydrocephalus. Twenty-four infants with hydrocephalus underwent noninvasive ICP measurement, magnetic resonance imaging and TCD before and after cerebrospinal fluid (CSF) diversion. The TCD indices were paired to the anterior fontanelle pressure findings and compared for correlation. After CSF diversion, ICP decreased significantly from 21.8 cm H(2)O to 7.7 cm H(2)O (p0.005). The transsystolic time (TST) as measured with TCD increased significantly from 176 to 221 ms (p0.005), whereas the pulsatility index (PI) decreased significantly from 1.3 to 1.0 (p0.05). The resistance index (RI) decreased significantly from 0.73 to 0.63 (p0.05). Mean bloodflow velocity through the middle cerebral artery increased significantly from 55.5 to 75.8 cm/s (p0.005). TST has a strong correlation with the ICP (p0.005). Measuring TST with TCD can be helpful in the decision-making process about whether to perform CSF diversion in infants with hydrocephalus. Because TST is related solely to the relative changes in the flow velocity caused by intracranial physical properties, it has a closer relation to ICP than the PI and the RI.

OBJECTIVE To define the clinical value of the flow replacement bypass using the excimer laser-assisted nonocclusive anastomosis (ELANA) technique in the treatment of patients with a noncoilable, nonclippable giant intracranial aneurysm of the middle cerebral artery (MCA). METHODS Between 1999 and 2006, 22 patients with a giant intracranial aneurysm of the MCA were treated in our hospital with an ELANA flow replacement bypass and MCA occlusion. We collected data on patient characteristics, operative aspects, complications, and functional health scores using the modified Rankin Scale. Mean follow-up was 3.6 years (range, 0.2–7.7 yr). RESULTS We were able to construct a patent bypass in 20 (91%) of 22 patients. All 34 ELANA attempts resulted in a patent anastomosis with a strong backflow directly after ELANA catheter retraction. The patients did not need to undergo temporary occlusion in any of the ELANA constructions. Mean ± standard deviation intracranial-to-intracranial bypass flow was 53 ± 13 ml/min. MCA aneurysm treatment was attempted in all 20 patients who had a patent bypass and was successful in 19 of them. There was a fatal hemorrhagic complication in one patient (5%), a nonfatal hemorrhagic complication in three patients (14%), and a nonfatal ischemic complication in six patients (27%). At follow-up, 17 patients (77%) had a functionally favorable outcome (modified Rankin Scale score at follow-up was the same as or less than the preoperative modified Rankin Scale score). All of these patients were independent at follow-up (modified Rankin Scale score ≤2). CONCLUSION This study demonstrates satisfactory results in the treatment of giant MCA aneurysms with an ELANA flow replacement bypass, considering the very grave natural history and treatment complexity of these lesions. The ELANA technique is a useful tool in the treatment armamentarium of the vascular neurosurgeon.

Transcranial magnetic stimulation (TMS) is a noninvasive activation method that is increasingly used for motor mapping. Preoperative functional mapping in vascular surgery is not routinely performed; however, in cases of high-grade arteriovenous malformations (AVMs), it could play a role in preoperative decision making. A 16-year-old male was suffering from a giant, right-sided insular, Spetzler-Martin Grade V AVM. This patient's history included 3 hemorrhagic strokes in the past 3 years, resulting in Medical Research Council Grade 2–3 (proximal) and 2–4 (distal) paresis of the left side of the body and hydrocephalus requiring a ventriculoperitoneal shunt. Preoperative TMS showed absent contralateral innervation of the remaining left-sided motor functions. Subsequently, the AVM was completely resected without any postoperative increase of the left-sided paresis. This case shows that TMS can support decision making in AVM treatment by mapping motor functions.

✓ Beckwith–Wiedemann syndrome (BWS) is a rare congenital syndrome characterized by gigantism, macroglossia, exophthalmos, postpartum hypoglycemia, and multiple midline defects such as omphalocele. The authors describe, to the best of their knowledge, the first case of a child in whom BWS was diagnosed and who was subsequently treated for a nasal encephalocele. Because the authors believe that this feature might not be an incidental finding in patients with BWS, intranasal masses in these patients should be carefully differentiated, as complications might be severe.

Introduction We report about a spina bifida patient with myelomeningocele at the lumbar level L5, extensive Chiari malformation type II with vermal herniation reaching to C6 with downward pontine shift, and a severe hypoplastic cerebellum. Chromosomal diagnostic tests showed no abnormalities. Case report The infant experienced severe central apneas successfully treated with oxygen therapy and caffeine medication; functional motor level was established at L5 with sparse anal sphincter function. Discussion After surgical intervention (myelomeningocele repair and ventriculoperitoneal shunt placement), these abnormalities significantly improved on radiological imaging; the preoperative hypoplastic, almost undetectable, cerebellum developed to a fair sized cerebellum. Apneas disappeared over time and the patient showed further developmental improvement. Herein, we illustrate and discuss the changes of the cerebellar volume before and after neurosurgical intervention.

A patient undergoing regular haemodialysis for chronic renal insufficiency developed neck pain followed by progressive spinal cord compression due to subluxation at the level C3-4. Decompression, laminectomy and osteosynthesis led to an almost complete recovery. A review of all the histological specimens suggested that hyperparathyroidism and not amyloidosis caused the vertebral destruction.

e20628Background: In NSCLC patients harboring specific genetic changes, such as ALK rearrangement and EGFR mutations, targeted therapies have exhibited considerable therapeutic potential. As the ge...

Summary Objective/Aims: To identify factors influencing perioperative blood loss and transfusion practice in craniosynostotic corrections. Background: Craniosynostotic corrections are associated with large amounts of blood loss and high transfusion rates. Methods: A retrospective analysis was performed of all pediatric craniosynostotic corrections during the period from January 2003 to October 2009. The primary endpoint was the receipt of an allogeneic blood transfusion (ABT) during or after surgery. Pre-, intra-, and postoperative data were acquired using the electronic hospital registration systems and patients’ charts. Results: Forty-four patients were operated using open surgical techniques. The mean estimated blood loss during surgery was 55 ml·kg−1. In 42 patients, red blood cells were administered during or after surgery with a mean of 38 ml·kg−1. In 23 patients, fresh frozen plasma was administered with a mean of 28 ml·kg−1. A median of two different donors per recipient was found. Longer duration of surgery and lower bodyweight were associated with significantly more blood loss and red blood cell transfusions. Higher perioperative blood loss and surgery at an early age were correlated with a longer duration of admission. Conclusions: In this study, craniosynostotic corrections were associated with large amounts of blood loss and high ABT rates. The amount of ABT could possibly be reduced by appointing a dedicated team of physicians, by using new less-invasive surgical techniques, and by adjusting anesthetic techniques.

Objective:To report microvascular decompression as a possible effective treatment for patients with nervus intermedius neuralgia, and to contribute to the literature regarding both this syndrome and this specific form of treatment.Method:Case report of a patient with intermedius neuralgia. The main complaint was severe otalgia in the area innervated by the nervus intermedius, possibly caused by neurovascular compression of the nervus intermedius by the anterior inferior cerebellar artery. Microvascular decompression was undertaken, with good results.Results:Post-operatively, the patient felt immediate and total relief of her otalgia, with normal facial nerve function and no otological morbidity. One year post-operatively, she was still free from otalgia.Conclusion:Patients with nervus intermedius neuralgia who do not respond to medical treatment may benefit from microvascular decompression.

To determine if changes in endometrial expression of the enzymes and receptors involved in prostaglandin (PG) synthesis and action might provide insights into the PGs involved in the initiation of decidualization, ovariectomized steroid-treated rats at the equivalent of day 5 of pseudopregnancy were given a deciduogenic stimulus and killed at various times up to 32 h thereafter. The expression of PG-endoperoxide synthases (PTGS1 and PTGS2), microsomal PGE synthases (PTGES and PTGES2), cytosolic PGE synthase (PTGES3), prostacyclin synthase (PTGIS), prostacyclin receptor, peroxisome proliferator-activated receptor δ (PPARD) and retinoid x receptor α (RXRA) in endometrium was assessed by semiquantitative RT-PCR, western blot analyses and immunohistochemistry. In addition, to determine which PG is involved in mediating decidualization, we compared the ability of PGE2, stable analogues of PGI2, L165041 (an agonist of PPARD), and docasahexanoic acid (an agonist of RXRA) to increase endometrial vascular permeability (EVP, an early event in decidualization), and decidualization when infused into the uterine horns of rats sensitized for the decidual cell reaction (DCR). EVP was assessed by uterine concentrations of Evans blue 10 h after initiation of infusions. DCR was assessed by the uterine mass 5 days after the initiation of the infusions. Because enzymes associated with the synthesis of PGE2, including PTGS2, are up-regulated in response to a deciduogenic stimulus and because PGE2 was more effective than the PGI2 analogues and PPARD and RXRA agonists in increasing EVP and inducing decidualization, we suggest that PGE2 is most likely the PG involved in the initiation of decidualization in the rat.

✓ The authors present the case of a 4-year-old boy in whom a medulloblastoma in the left cerebellar hemisphere was successfully resected with no signs of residual tumor on the postoperative magnetic resonance (MR) images. A second MR imaging study performed 1 month after surgery demonstrated an extensive, contrast-enhancing lesion in the left cerebellar hemisphere, which simulated massive recurrent tumor, and repeated surgery was considered. A third postoperative MR imaging study, performed for evaluation of the craniospinal axis 10 days after the second postoperative study, still showed some contrast enhancement in the left cerebellar hemisphere, but the lesion had almost disappeared. Postoperative hemicerebellar inflammation seemed to be the most likely explanation. This case illustrates that early postoperative inflammation can mimic recurrent tumor on MR images obtained after resection of a medulloblastoma and caution should be taken in interpreting such images. Clinical history, neurological examination, laboratory findings, and repeated MR imaging studies can be helpful in evaluating the patient accurately.

The authors present the case of a 2-year-old boy with bobble-head doll syndrome (BHDS) associated with a large suprasellar arachnoid cyst and enlarged ventricles, who was successfully treated with neuronavigated laser-assisted endoscopic ventriculocystocisternostomy. The clinical history, surgical treatment, and clinical follow up of the patient are described. A navigated laser-assisted endoscopic ventriculocystocisternostomy of the suprasellar arachnoid cyst led to cessation of the head bobbing, and notable reduction of the cyst and ventricles was visible on the postoperative magnetic resonance images. Caused by a suprasellar arachnoid cyst, BHDS can be successfully treated with navigated laser-assisted endoscopic ventriculocystocisternostomy. The advantages of this procedure are minimal invasiveness and facilitated guidance of the neuronavigation system to the target area when normal anatomical landmarks are not visible.

The aim of this report is to introduce a simple modification to the free-hand frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles. In this technical note, we describe our experience with ventricular catheter placement in two children suffering from shunt dependent idiopathic intracranial hypertension using an image-guided instrument holder with a catheter guide. In both patients, the surgical procedure proved to be easy and accurate, with good initial clinical results. The use of an image-guided instrument holder is a modification to the free-hand frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles.

In the theoretical analysis of arterial networks the existence of geometric optimisation has long been suggested, although observational studies have not yet fully corroborated these theories. Since this could be due to experimental flaws, the aim of this study was to establish the validity of arterial geometric optimisation using a new experimental design and to assess the influence of ageing. Solid vascular casts of arterial mesenteric branching systems of 8-wk-old and adult dogs (beagles) were used to examine vascular diameters and branching angles, the latter in a manner that allowed optimisation of the line of view, thus minimising distortion errors due to a line of view not normal to the branching plane. Internal and external vessel diameters were found to be in accordance with the theoretical principle of minimum work (8-wk-old internal: r = 0.994; adult internal: r = 0.971; adult external: r = 0.985). Although branching angles were found to be in agreement with basic qualitative principles of arterial branching geometry, the measurements still showed a large amount of scatter and were generally smaller than expected on theoretical grounds, despite the newly designed measuring technique. These branching angles demonstrated small age-related differences. However, when biological cost was considered per bifurcation, surprisingly, guidance towards minimum lumen volume and pumping power with increase in age could clearly be demonstrated (P

Background Myeloid sarcoma is an extramedullary manifestation of haematologic malignancy, most commonly acute myeloid leukemia (AML), which can cause neurological symptoms. Case description A 45-year-old male with a history of AML presented with a lumbosacral nerve root entrapment syndrome followed by cauda equina compression, but without systemic signs of AML recurrence. MRI showed a mass compressing the spinal cord at level L5–S2. After surgically removing the tumour pathologic examination yielded a myeloid sarcoma. Combined chemotherapy and radiation therapy followed. Five months later the patient developed a thoracal (Th10–Th11) radiculopathy due to a relapse of the myeloid sarcoma, followed by C8-Th1-radiculopathy caused by leptomeningeal spread. Conclusion This case forms the first description of recurrent, multifocal and progressive radiculopathy due to myeloid sarcoma. This diagnosis should be considered in patients with radiculopathy with previous haematological malignancy and/or signs or symptoms of such disease; the absence of systemic disease activity does not rule out myeloid sarcoma.