Exosomal miRNA in early-stage hepatocellular carcinoma.

The incidence and mortality of hepatic carcinoma (HCC) remain high, and early diagnosis of HCC is seen as a key approach in improving clinical outcomes. However, the sensitivity and specificity of current early screening methods for HCC are not satisfactory. In recent years, research around exosomal miRNA has gradually increased, and these molecules have emerged as attractive candidates for early diagnosis and treatment of HCC. This review summarizes the feasibility of using miRNAs in peripheral blood exosomes as early diagnostic tools for HCC.

Removing a suprapatellar intramedullary nail via a suprapatellar approach: a retrospective cohort study.

BACKGROUND: Over the last 20 years, suprapatellar (SP) intramedullary nailing has gained considerable attention for treating tibia fractures and is believed to improve fracture alignments, decrease anterior knee pain, and facilitate intraoperative fluoroscopy. However, it is associated with various concerns, including the need to make another infrapatellar (IP) incision to remove the nail. AIMS: This study was aimed at developing a new technique for the removal of SP tibial nails through an SP approach using a cannulated extraction system. The efficiency of the novel SP approach was compared to that of the traditional IP approach for the removal of SP tibial nails. PATIENTS AND METHODS: This was a retrospective cohort study from a prospectively collected clinical registry. The data for 69 consecutive patients who received surgery to remove a previous SP intramedullary nail using an SP approach (n = 30, SP cohort) or an IP approach (n = 39, IP cohort) were analyzed. Intra-operative evaluations included intraoperative blood loss, operation time, and changes in the surgical procedures. At six months follow-up, post-operative Lysholm knee score, visual analog scale (VAS) score, and the active range of motion (ROM) of the affected knee and complications were assessed. RESULTS: Patients in the SP cohort exhibited an increased post-operative Lysholm knee score (ß, 2.6; 95% confidence interval [CI], 0.6 to 4.6; P = 0.012), decreased post-operative VAS score (ß, - 0.7; 95% CI, - 1.1 to - 0.2; P = 0.004), and increased operation time (ß, 9.8 minutes; 95% CI, 5.7 to 14.0 minutes; P < 0.001) compared with those treated with the IP approach after adjustment for baseline characteristics. There were no statistically significant differences in blood loss, post-operative ROM, or complications between the two cohorts. CONCLUSIONS: Compared with the IP technique, the SP approach for the removal of an SP tibial nail was independently associated with an increased post-operative Lysholm knee score and decreased VAS score, although the surgery was longer in duration. The novel technique offers a reliable and minimally invasive option for the removal of an SP tibial nail.

Preoperative MRI Classification May Not Predict Symptom Relief after Uterine Artery Embolization in Patients with Adenomyosis.

OBJECTIVE: To investigate the association between magnetic resonance imaging (MRI) classification and symptom relief after uterine artery embolization (UAE) in patients with adenomyosis. METHODS: Totally, 73 patients with symptomatic adenomyosis who underwent UAE were retrospectively analyzed. Preoperative MRI classification was defined as: type I, high signal on both T2-weighted images (T2WI) and T1-weighted images (T1WI); type III, high signal only on T2WI, and type II, high signal on neither T1WI nor T2WI. Dysmenorrhea was measured with the visual-analog scales and the degree of menorrhagia was measured according to the number of sanitary pads used in one menstrual cycle. Dysmenorrhea and menorrhagia were measured before UAE and 12 months after UAE. RESULTS: The number of the type I, II, III cases was 23, 37, and 13, respectively. The baseline characteristics of the three groups exhibited no significant difference. The alleviation rates of dysmenorrhea among type I, II, III cases were 73.9%, 89.2%, and 84.6%, respectively (P=0.455). The alleviation rates of menorrhagia for type I, II, III were 69.6%, 78.4%, and 92.3%, respectively (P=0.714). CONCLUSION: Pre-procedure MRI classification and symptom relief after UAE exhibited no significant association. UAE has a favorable mid-term control on dysmenorrhea and menorrhagia among patients with adenomyosis. Preoperative MRI classification might not indicate symptom relief. More research is needed before changing clinical practice.

Phylogeny and biogeography of the Japanese rhinoceros beetle, Trypoxylus dichotomus (Coleoptera: Scarabaeidae) based on SNP markers.

The Japanese rhinoceros beetle Trypoxylus dichotomus is one of the largest beetle species in the world and is commonly used in traditional Chinese medicine. Ten subspecies of T. dichotomus and a related Trypoxylus species (T. kanamorii) have been described throughout Asia, but their taxonomic delimitations remain problematic. To clarify issues such as taxonomy, and the degree of genetic differentiation of Trypoxylus populations, we investigated the genetic structure, genetic variability, and phylogeography of 53 specimens of Trypoxylus species from 44 locations in five Asian countries (China, Japan, Korea, Thailand, and Myanmar). Using specific-locus amplified fragment sequencing (SLAF-seq) techniques, we developed 330,799 SLAFs over 114.16M reads, in turn yielding 46,939 high-resolution single nucleotide polymorphisms (SNPs) for genotyping. Phylogenetic analysis of SNPs indicated the presence of three distinct genetic groups, suggesting that the various subspecies could be treated as three groups of populations. PCA and ADMIXTURE analysis also identified three genetic clusters (North, South, West), which corresponded to their locations, suggesting that geographic factors were important in maintaining within population homogeneity and between population divergence. Analyses of SNP data confirmed the monophyly of certain subspecies on islands, while other subspecies (e.g., T. d. septentrionalis) were found to be polyphyletic and nested in more than one lineage. AMOVA demonstrated high level of differentiation among populations/groups. Also, pairwise F ST values revealed high differentiation, particularly between South and West, as well as between North and South. Despite the differentiation, measurable gene flow was inferred between genetic clusters but at varying rates and directions. Our study demonstrated that SLAF-seq derived markers outperformed 16S and COII sequences and provided improved resolution of the genetic differentiation of rhinoceros beetle populations from a large part of the species' range.

Nanotechnology Assisted Chemotherapy for Targeted Cancer Treatment: Recent Advances and Clinical Perspectives.

Nanotechnology has recently provided exciting platforms in the field of anticancer research with promising potentials for improving drug delivery efficacy and treatment outcomes. Nanoparticles (NPs) possess different advantages over the micro and bulk therapeutic agents, including their capability to carry high payloads of drugs, with prolonged half-life, reduced toxicity of the drugs, and increased targeting efficiency. The wide variety of nanovectors, coupled with different conjugation and encapsulation methods available for different theranostic agents provide promising opportunities to fine-tune the pharmacological properties of these agents for more effective cancer treatment methods. This review discusses applications of NPs-assisted chemotherapy in preclinical and clinical settings and recent advances in design and synthesis of different nanocarriers for chemotherapeutic agents. Moreover, physicochemical properties of different nanocarriers, their impacts on different tumor targeting strategies and effective parameters for efficient targeted drug delivery are discussed. Finally, the current approved NPs-assisted chemotherapeutic agents for clinical applications and under different phases of clinical trials are discussed.

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) predict the occurrence of hyperleukocytosis and arsenic metabolism in APL patients treated with As2O3.

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. High-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) was used to determine the concentrations of plasma arsenic metabolites. Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. Conversely, we did not observe statistically significant associations between the occurrence of hyperleukocytosis and AS3MT 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) polymorphisms in our study subjects. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3.

[Research progress of super enhancer in cancer].

Super enhancers (SEs) are composed of clusters of enhancers in close genomic proximity. They constitute a large family of regulatory elements that specify gene expression patterns and cell identity. SE regions consist of unusually strong enrichment of binding sites for transcriptional factors, cofactors, and enhancers associated with epigenetic modifications. SEs play important roles in regulating the aberrant gene expression in tumor cells. Via SEs, cancer cells activate the expression of various oncogenes, and promote cell proliferation, invasion and migration properties. Hence suppression of SEs activities could inhibit the growth and survival of cancer cells. In this review, we summarize the fundamental principles, functions and regulation of super enhancers and therapeutic potential in targeting SEs in cancer cells, thereby introducing and providing new conceptions for development of antineoplastic drugs.

Application of the Chinese Aircraft-shaped Sleeve system in the treatment of tibial shaft fractures using a suprapatellar approach for tibial intramedullary nailing: a randomised controlled trial.

BACKGROUND: The use of the suprapatellar approach for intramedullary nailing has recently become popular for the treatment of tibial fractures. This study aimed to investigate the effectiveness of using the Chinese Aircraft-shaped Sleeve (CASS) system on the clinical outcomes of tibial intermedullary nailing using a suprapatellar approach for the treatment of tibial fractures in a cohort of adult Chinese patients. METHODS: Magnetic resonance images (MRI) of the knee joints of 212 healthy adults with normal lower limb function from May 2011 to May 2015 were obtained from a level I Chinese regional trauma centre. Sixty inpatients at the same trauma centre who underwent treatment for tibial shaft fractures from June 2015 to June 2018 were enrolled. Tibial intramedullary nailing fixation of tibial shaft fractures via the suprapatellar approach was performed with either a CASS system or a conventional sleeve. The measurements of patellofemoral joint anatomy, the surgical time, the assessments of the patellofemoral joint cartilage conditions, and information of residual debris based on arthroscopic analysis were subsequently collected. RESULTS: The mean patellar angle (PA), sulcus angle (SA), sulcus width (SW) and sulcus depth (SD) were 135.40 ± 6.20°, 142.37 ± 5.33°, 33.37 ± 2.73 mm, and 4.29 ± 0.63 mm, respectively. The surgical time until entry reaming commencement and the irrigation time were significantly lower in the CASS group (P < 0.001). The difference in cartilage damage rate between groups was statistically significant (P = 0.031); the difference in residual debris conditions was not statistically significant (P = 0.1967). CONCLUSION: The use of the CASS system could improve clinical outcomes of intramedullary nailing via suprapatellar approach for patients with a small patellofemoral joint space.

Ablative Hypofractionated Radiation Therapy Enhances Non-Small Cell Lung Cancer Cell Killing via Preferential Stimulation of Necroptosis In Vitro and In Vivo.

PURPOSE: To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT). METHODS AND MATERIALS: Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo. RESULTS: Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05). CONCLUSIONS: Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy.

Excessive activated T-cell proliferation after anti-CD19 CAR T-cell therapy.

Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19+ diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (fludarabine/cyclophosphamide). The lymphocyte count in the peripheral blood (PB) increased to 77 × 109/L on day 13 post infusion, and the proportion of CD8+ actived T cells was 93.06% of the lymphocytes. Then, the patient suffered from fever and hypoxaemia. Significant increases in serum cytokine, lactate dehydrogenase, aspartate aminotransferase (AST), alanine transaminase (ALT), and glutamic-oxalacetic transaminase (γ-GT) levels were observed. A high-throughput sequencing analysis for T-cell receptors (TCRs) and whole-genome sequencing were used to explore the mechanisms underlying this excessive T-cell proliferation. TCR diversity was demonstrated, but no special gene mutation was found. The patient was found to be infected with the John Cunningham polyomavirus (JCV). It cannot be ruled out the bystander activation pathway induced by JCV infections related the excessive activated T-cell proliferation. Although the clinical and laboratory data do not fully explain the reason for excessive T-cell proliferation after the anti-CD19 CAR T-cell infusion, the risk of this type of toxicity should be emphasized. This study was registered at www.clinicaltrials.gov as NCT01864889.

Synergetic Toughening Effect of Carbon Nanotubes and ß-Nucleating Agents on the Polypropylene Random Copolymer/Styrene-Ethylene-Butylene- Styrene Block Copolymer Blends.

Polypropylene random co-polymer (PPR)/styrene-ethylene-butylene-styrene (SBS) block copolymer blends with high toughness and favorable tensile properties were successfully obtained by blending with traces of multi-wall carbon nanotubes (MWCNTs) and ß-nucleating agents (ß-NAs). ß-NAs can effectively induce the ductile ß-form crystal in the PPR matrix. Although the addition of MWCNTs was reported to be only benefit for the tensile strength of PPR and relatively disadvantageous for the toughness, the obviously synergistic toughening effect in PPR/SBS blends was found when MWCNTs and ß-NAs coexisted. The notched izod impact strength of PPR/30 wt % SBS blend with MWCNTs and ß-NAs increased from 11.3 to 58.9 kJ/m²; more than 5-fold increment compared with pure PPR. Meanwhile, the tensile strength retention of this PPR blend is still above 72.2%. The micro-morphology indicated that the MWCNTs can act as bridges between SBS particle and PPR matrix, effectively transferring the stress and absorbing impact energy among SBS particles.

Partial resection and reconstruction of the sternum for treatment of metachronous sternal metastasis of thyroid carcinoma: A case report.

RATIONALE: Metachronous sternal metastasis of thyroid carcinoma was a rare disease. There was no consensus in the treatment for bone metastasis after the initial thyroid carcinoma surgery. PATIENT CONCERNS: A 53-year-old female patient was hospitalized due to recurrent dull chest pains, with a history of radical right side thyroid carcinoma 4 years ago. On examination, there was an irregular mass on the lower left half of the sternum. Computerized tomography scan showed sternal bone destruction with a soft tissue mass. DIAGNOSES: Metachronous sternal metastasis of thyroid carcinoma. INTERVENTIONS: Partial resection of the sternum and reconstruction with a titanium alloy mesh were performed. OUTCOMES: After a 3-year follow-up, the patient had no recurrence. LESSONS: Surgical resection may be a sufficient treatment for metachronous sternal metastasis of thyroid carcinoma. Biosynthesis material mesh is preferred to be used.

Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.

Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial.

Purpose: Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma.Experimental Design: Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).Results: Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 107 CAR-positive T cell per kg (SD, 0.25; range, 1.1-2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.Conclusions: CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment. Clin Cancer Res; 23(5); 1156-66. ©2016 AACR.

Up- and Down-regulated Leukemia-related Protein 16 Affects ERα Expression and Prolactin Secretion by GH3 Cells.

Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16) is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor α (ERα) in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old) were randomly divided into five groups of 10 rats each. After 120 days of treatment, the rats were sacrificed, and the expression of LRP16 and ERα were examined by Western blot and immunohistochemistry to explore the changes in ERα, LRP16, and prolactin. After siRNA transfection of the respective genes, the GH3 cells were cultured, and their secretory function as well as the expression of ERα mRNA and prolactin were analyzed by enzyme-linked immunosorbent assay and real-time-polymerase chain reaction analysis. The results show that secretion of prolactin by GH3 cells can be affected by up and downregulating LRP16 expression, which may provide a novel medical therapy in clinical trials.

Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy.

While the mechanisms underlying apoptosis and autophagy have been well characterized over recent decades, another regulated cell death event, necroptosis, remains poorly understood. Elucidating the signaling networks involved in the regulation of necroptosis may allow this form of regulated cell death to be exploited for diagnosis and treatment of cancer, and will contribute to the understanding of the complex tumor microenvironment. In this review, we have summarized the mechanisms and regulation of necroptosis, the converging and diverging features of necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy, as well as attempts to exploit this newly gained knowledge to provide therapeutics for cancer.

Stereotactic body radiation therapy for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph nodes or postoperative stump including pancreatic stump and other stump.

BACKGROUND AND AIM: The aim of this study is to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using CyberKnife in the treatment of patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. PATIENTS AND METHODS: Between October 1, 2006 and May 1, 2015, patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery were enrolled and treated with SBRT at our hospital. The primary end point was local control rate after SBRT. Secondary end points were overall survival, time to symptom alleviation, and toxicity, assessed using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Twenty-four patients with 24 lesions (17 abdominal lymph nodes and seven stumps) were treated with SBRT, of which five patients presented with abdominal lymph nodes and synchronous metastases in the liver and lung. The 6-, 12-, and 24-month actuarial local control rates were 95.2%, 83.8%, and 62.1%, respectively. For the entire cohort, the median overall survival from diagnosis and SBRT was 28.9 and 12.2 months, respectively. Symptom alleviation was observed in eleven of 14 patients (78.6%) within a median of 8 days (range, 1-14 days) after SBRT. Nine patients (37.5%) experienced Common Terminology Criteria for Adverse Events version 4.0 grade 1-2 acute toxicities; one patient experienced grade 3 acute toxicity due to thrombocytopenia. CONCLUSION: SBRT is a safe and effective treatment for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Further studies are needed before SBRT can be recommended routinely.

Mesenchymal stem cells generate pericytes to promote tumor recurrence via vasculogenesis after stereotactic body radiation therapy.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is postulated to enhance the recruitment of mesenchymal stem cells (MSCs) into the tumor microenvironment, which promote tumor recurrence. The aim of this study is to determine the molecular mechanisms behind SBRT stimulating MSC migration and differentiation. METHODS: In vitro, mediated factors and migrated MSCs (post-SBRT) were generated. In vivo, bone-marrow derived MSCs were identified and harvested from green fluorescent protein (GFP)-expressing transgenic male mice and transplanted into sub-lethally irradiated recipient female mice to establish a model of bone marrow transplantation. Lewis lung carcinoma and malignant melanoma-bearing recipient mice were treated with SBRT, 14 Gy/1 fraction. The migration and differentiation potential of MSCs were characterized. RESULTS: SBRT increased the release of stromal cell derived factor-1α (SDF-1α) and platelet-derived growth factor-B (PDGF-B) by tumor cells; these ligands bound to chemokine (C-X-C motif) receptor 4 (CXCR4) and platelet-derived growth factor receptor-ß (PDGFR-ß), respectively, on circulating bone marrow-derived MSCs, resulting in engraftment of the MSCs into the tumor parenchyma. The newly-homed MSCs differentiated into pericytes, which induced the tumor vasculogenesis, and promoted tumor regrowth. Targeted therapies, AMD3100 and imatinib abrogated MSC homing, vasculogenesis, and tumor regrowth. CONCLUSION: Bone-marrow derived MSCs migrate to the tumor parenchyma and differentiate into pericytes, inducing tumor vasculogenesis after SBRT, and promoting tumor recurrence. MSC migration and maturation may be abrogated with AMD3100 and imatinib. This novel treatment strategy warrants clinical investigation.

Clinical evaluation of stereotactic radiation therapy for recurrent or second primary mediastinal lymph node metastases originating from non-small cell lung cancer.

AIMS: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT, both stereotactic body RT [SBRT] and fractionated stereotactic RT [FSRT]) in the treatment of patients with recurrent or second primary mediastinal lymph node metastases (R/SP-MLNMs) originating from non-small cell lung cancer (NSCLC). METHODS: Between 10/2006 and 7/2013, patients with R/SP-MLNMs originating from NSCLC were enrolled and treated with SRT at our hospital; their data was stored in prospectively-collected database. The enrolled patients were divided into Group A (without prior RT) and Group B (with prior RT). The primary end-point was overall survival (OS). The secondary end-points were the MLNM local control (LC), the time to symptom alleviation, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). RESULTS: Thirty-three patients were treated (16 in Group A with 19 R/SP-MLNMs and 17 in Group B with 17 R/SP-MLNMs). For the entire cohort, the median OS was 25.5 months with a median follow-up of 20.9 months (range, 3.2-82). The 1-year and 3-year actuarial LC rates were 100% and 86%, respectively. Symptom alleviation was observed in 52% of patients, after a median of 6 days (range, 3-18). CTCAE v4.0 ≥ Grade 3 toxicities occurred in 5 patients (15%; all in Group B); among them, Grade 5 in 2 patients. CONCLUSIONS: We recommend exercising extreme caution in using SRT for R/SP-MLNMs in patients who received prior RT (particularly to LN station 7). For patients without previous RT, SRT appears to be safe and efficacious treatment modality; prospective studies are warranted.

Partial splenectomy using a laparoscopic bipolar radiofrequency device: a case report.

We report a 51-year-old female patient with a solitary lymphangioma located in the upper splenic pole which was managed successfully with laparoscopic partial splenectomy. Surgery lasted 170 min and did not require blood transfusions. The patient recovered well post-operatively and was asymptomatic at the 3-mo follow-up. She had a normal platelet count and no recurrence on ultrasonography or computed tomography. Laparoscopic partial splenectomy is a safe, minimally invasive technique for the treatment of solitary splenic lymphangiomas in the splenic pole. We performed the procedure using the Habib(TM) 4X device. This laparoscopic bipolar radiofrequency device ensured a "bloodless" splenic parenchymal resection.