Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicine for acute myeloid leukemia in elderly patients

Abstract

Background

The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion daunorubicin plus cytarabine (DA).

Patients and methods

Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m² BID days 1,3,5,7) plus mitoxantrone (10 mg/m² days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m² continuously days 1-7) plus daunorubicin (45 mg/m² days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.

Results

Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The CR rate after DA was 39% (95%-CI; 33-45) versus 55% (95%-CI; 49-61) after IMA (OR 1.89, p=0.001). The six-week early-death rate was 14% in both arms. Relapse-free survival (RFS) curves were superimposable in the first year, but separated afterwards, resulting in 3-year RFS rates of 29% versus 14% in the DA versus IMA arms, respectively (p=0.042). The median OS was 10 months in both arms (p=0.513).

Conclusion

The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate dose cytarabine in induction may improve curative treatment for elderly AML patients.

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Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

Ann Oncol 2017; 28: 1339–1345 (doi: 10.1093/annonc/mdx075)

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The Evolving Dilemma of Factor XI in Pregnancy: Suggestions for Management

A case of a patient with severe factor XI (FXI) deficiency who presented for her seventh labor and delivery is presented. The nature of FXI deficiency, its prevalence, and issues related to genetic screening are discussed. Published literature on the topic is reviewed, including criteria that were developed to assess bleeding, laboratory tools used to estimate bleeding risk, and available treatments. Within the context of this challenging clinical dilemma, specific recommendations are provided for the antepartum, intrapartum, and postpartum stages of pregnancy. These include recommendations that take into account both FXI levels and history of any abnormal bleeding. While there are effective treatments available, it is important to consider that institutional multidisciplinary protocols are needed to manage this complex disorder. More work is needed to define the best management protocols. Accepted for publication December 19, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Aryeh Shander, MD, Department of Anesthesiology, Englewood Hospital and Medical Center, 350 Engle St, Englewood, NJ 07631. Address e-mail to aryeh.shander@ehmchealth.org. © 2018 International Anesthesia Research Society

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Sex Difference of Angiotensin IV–, LVV-Hemorphin 7–, and Oxytocin-Induced Antiallodynia at the Spinal Level in Mice With Neuropathic Pain

Background: We demonstrated previously that angiotensin IV (Ang IV) and LVV-hemorphin 7 (LVV-H7) act through the blockade of insulin-regulated aminopeptidase to decrease oxytocin degradation, thereby causing antihyperalgesia at the spinal level in rats. We determined that intrathecal oxytocin can induce significant antihyperalgesia in male rats with inflammation but not in female rats. Thus, we speculate that Ang IV, LVV-H7, and oxytocin can induce antiallodynia, which could be of great therapeutic potential. Because the antihyperalgesia by using these peptides was with sex difference, their possible antiallodynia was examined in male and female mice for comparison. We investigated whether Ang IV, LVV-H7, and oxytocin produce antiallodynia at the spinal level in mice and whether this antiallodynia differs between the sexes. METHODS: Partial sciatic nerve ligation surgery was performed on adult male and female C57BL/6 mice from the same litter (25–30 g). The effects of intrathecal injections of Ang IV (25.8 nmol), LVV-H7 (27.2 nmol), and oxytocin (0.125 or 1.25 nmol) were assessed through the von Frey test 3 days after partial sciatic nerve ligation. RESULTS: Intrathecal injection of Ang IV, LVV-H7, and oxytocin all produced a potent antiallodynia in male mice. However, these antiallodynia effects were either extremely weak or absent in female mice at the same dose. CONCLUSIONS: Intrathecal Ang IV, LVV-H7, and oxytocin can all cause significant antiallodynia in male mice. The Ang IV-, LVV-H7-, and oxytocin-induced antiallodynia effects differed between the sexes at the spinal level in mice. Accepted for publication November 28, 2017. Funding: The study was supported by National Defense Medical Center, Taipei, Taiwan, and was funded by the Tri-Service General Hospital Songshan Branch, Taipei, Taiwan (TSGH-SSB-10407), and the Ministry of Science and Technology, Taiwan (103-2320-B-016-016-MY3). This manuscript was edited by Wallace Academic Editing The authors E. Y.-K. Huang and J.-H. Kao have contributed equal to this study. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Eagle Yi-Kung Huang, PhD and Jen-Hsin Kao, PhD, Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. Address e-mail to eyh58@mail.ndmctsgh.edu.tw and cindykao1128@gmail.com. © 2018 International Anesthesia Research Society

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A Systematic Review of Outcomes Associated With Withholding or Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Before Noncardiac Surgery

BACKGROUND: The global rate of major noncardiac surgical procedures is increasing annually, and of those patients presenting for surgery, increasing numbers are taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB). The current recommendations of whether to continue or withhold ACE-I and ARB in the perioperative period are conflicting. Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the increased incidence of postinduction hypotension; however, they have failed to correlate this with adverse patient outcomes. The aim of this meta-analysis was to determine whether continuation or withholding ACE-I or ARB therapy in the perioperative period is associated with mortality and major morbidity. METHODS: This meta-analysis was prospectively registered on PROSPERO (CRD42017055291). A comprehensive search of MEDLINE (PubMed), CINAHL (EBSCO host), ProQuest, Cochrane database, Scopus, and Web of Science was conducted on December 6, 2016. We included adult patients >18 years of age on chronic ACE-I or ARB therapy who underwent noncardiac surgery in which ACE-I or ARB was either withheld or continued on the morning of surgery. Primary outcomes included all-cause mortality and major cardiac events (MACE). Secondary outcomes included the risk of congestive heart failure, acute kidney injury, stroke, intraoperative/postoperative hypotension, and the length of hospital stay. RESULTS: After abstract review, the full text of 25 studies was retrieved, of which 9 fulfilled the inclusion criteria: 5 were randomized control trials, and 4 were cohort studies. These studies included a total of 6022 patients on chronic ACE-I/ARB therapy before noncardiac surgery. A total of 1816 patients withheld treatment the morning of surgery and 4206 continued their ACE-I/ARB. Preoperative demographics were similar between the 2 groups. Withholding ACE-I/ARB therapy was not associated with a difference in mortality (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.62–1.52; I2 = 0%) or MACE (OR, 1.12; 95% CI, 0.82–1.52; I2 = 0%). However, withholding therapy was associated with significantly less intraoperative hypotension (OR, 0.63; 95% CI, 0.47–0.85; I2 = 71%). No effect estimate could be pooled concerning length of hospital stay and congestive heart failure. CONCLUSIONS: This meta-analysis did not demonstrate an association between perioperative administration of ACE-I/ARB and mortality or MACE. It did, however, confirm the current observation that perioperative continuation of ACE-I/ARBs is associated with an increased incidence of intraoperative hypotension. A large randomized control trial is necessary to determine the appropriate perioperative management of ACE-I and ARBs. Accepted for publication December 19, 2017. Funding: No outside funding was utilized in the search and retrieval of all articles. All funding was from departmental resources. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). PROSPERO registry: CRD42017055291. Reprints will not be available from the authors. Address correspondence to Caryl Hollmann, MBChB, DA (SA), Department of Anaesthesia and Perioperative Medicine, D23, Groote Schuur Hospital, University of Cape Town, Observatory, Cape Town 7925, South Africa. Address e-mail to carylhollmann@gmail.com. © 2018 International Anesthesia Research Society

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Activation of Melatonin Receptors by Ramelteon Induces Cardioprotection by Postconditioning in the Rat Heart

Activation of melatonin receptors protects the heart against ischemia-reperfusion injury. Ramelteon, a clinically used drug for insomnia, acts via activation of melatonin receptors. We investigated whether ramelteon induces acute infarct size reduction by postconditioning. Male Wistar rats were randomized to 6 groups. Hearts were treated with melatonin and ramelteon at the beginning of reperfusion. The melatonin receptor inhibitor luzindole was administered with and without melatonin and ramelteon, respectively. Ramelteon reduced infarct size to the same extent as melatonin. Both effects were completely abolished by luzindole. The results show for the first time that ramelteon induces cardioprotection by postconditioning. Accepted for publication September 27, 2017. Funding: This work was supported by departmental funding only. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Ragnar Huhn, MD, PhD, Department of Anesthesiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany. Address e-mail to Ragnar.Huhn@med.uni-duesseldorf.de. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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Flupirtine: A Less-Explored, Neglected Nonopioid Analgesic

No abstract available

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Misguided by INR in Liver Disease Patients? Implications for Clinicians Including Pain Proceduralists

No abstract available

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ABC of Clinical Leadership, 2nd ed

No abstract available

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Summative Objective Structured Clinical Examination Assessment at the End of Anesthesia Residency for Perioperative Ultrasound

While standardized examinations and data from simulators and phantom models can assess knowledge and manual skills for ultrasound, an Objective Structured Clinical Examination (OSCE) could assess workflow understanding. We recruited 8 experts to develop an OSCE to assess workflow understanding in perioperative ultrasound. The experts used a binary grading system to score 19 graduating anesthesia residents at 6 stations. Overall average performance was 86.2%, and 3 stations had an acceptable internal reliability (Kuder–Richardson formula 20 coefficient >0.5). After refinement, this OSCE can be combined with standardized examinations and data from simulators and phantom models to assess proficiency in ultrasound. Accepted for publication December 11, 2017. Funding: This study was funded by the Foundation for Anesthesia Research and Education (FAER) as part of a grant awarded to Robina Matyal. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). J. D. Mitchell and R. Amir contributed equally to this work. Reprints will not be available from the authors. Address correspondence to John D. Mitchell, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, RB-470, Boston, MA 02215. Address e-mail to jdmitche@bidmc.harvard.edu. © 2018 International Anesthesia Research Society

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Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicine for acute myeloid leukemia in elderly patients

Abstract

Background

The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion daunorubicin plus cytarabine (DA).

Patients and methods

Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m² BID days 1,3,5,7) plus mitoxantrone (10 mg/m² days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m² continuously days 1-7) plus daunorubicin (45 mg/m² days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.

Results

Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The CR rate after DA was 39% (95%-CI; 33-45) versus 55% (95%-CI; 49-61) after IMA (OR 1.89, p=0.001). The six-week early-death rate was 14% in both arms. Relapse-free survival (RFS) curves were superimposable in the first year, but separated afterwards, resulting in 3-year RFS rates of 29% versus 14% in the DA versus IMA arms, respectively (p=0.042). The median OS was 10 months in both arms (p=0.513).

Conclusion

The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate dose cytarabine in induction may improve curative treatment for elderly AML patients.

http://ift.tt/2DMbt2V

Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

Ann Oncol 2017; 28: 1339–1345 (doi: 10.1093/annonc/mdx075)

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Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG)

Abstract

Mixed reports leave uncertainty about whether normalization of apparent diffusion coefficient (ADC) to a within-subject white matter reference is necessary for assessment of tumor cellularity. We tested whether normalization improves the previously reported correlation of resection margin ADC with 15-month overall survival (OS) in HGG patients. Spin-echo echo-planar DWI was retrieved from 3 T MRI acquired between maximal resection and radiation in 37 adults with new-onset HGG (25 glioblastoma; 12 anaplastic astrocytoma). ADC maps were produced with the FSL DTIFIT tool (Oxford Centre for Functional MRI). 3 neuroradiologists manually selected regions of interest (ROI) in normal appearing white matter (NAWM) and in non-enhancing tumor (NT) < 2 cm from the margin of residual enhancing tumor or resection cavity. Normalized ADC (nADC) was computed as the ratio of absolute NT ADC to NAWM ADC. Reproducibility of nADC and absolute ADC among the readers' ROI was assessed using intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wCV). Correlations of ADC and nADC with OS were compared using receiver operating characteristics (ROC) analysis. A p value 0.05 was considered statistically significant. Both mean ADC and nADC differed significantly between patients subgrouped by 15-month OS (p = 0.0014 and 0.0073 respectively). wCV and ICC among the readers were similar for absolute and normalized ADC. In ROC analysis of correlation with OS, nADC did not perform significantly better than absolute ADC. Normalization does not significantly improve the correlation of absolute ADC with OS in HGG, suggesting that normalization is not necessary for clinical or research ADC analysis in HGG patients.

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Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG)

Abstract

Mixed reports leave uncertainty about whether normalization of apparent diffusion coefficient (ADC) to a within-subject white matter reference is necessary for assessment of tumor cellularity. We tested whether normalization improves the previously reported correlation of resection margin ADC with 15-month overall survival (OS) in HGG patients. Spin-echo echo-planar DWI was retrieved from 3 T MRI acquired between maximal resection and radiation in 37 adults with new-onset HGG (25 glioblastoma; 12 anaplastic astrocytoma). ADC maps were produced with the FSL DTIFIT tool (Oxford Centre for Functional MRI). 3 neuroradiologists manually selected regions of interest (ROI) in normal appearing white matter (NAWM) and in non-enhancing tumor (NT) < 2 cm from the margin of residual enhancing tumor or resection cavity. Normalized ADC (nADC) was computed as the ratio of absolute NT ADC to NAWM ADC. Reproducibility of nADC and absolute ADC among the readers' ROI was assessed using intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wCV). Correlations of ADC and nADC with OS were compared using receiver operating characteristics (ROC) analysis. A p value 0.05 was considered statistically significant. Both mean ADC and nADC differed significantly between patients subgrouped by 15-month OS (p = 0.0014 and 0.0073 respectively). wCV and ICC among the readers were similar for absolute and normalized ADC. In ROC analysis of correlation with OS, nADC did not perform significantly better than absolute ADC. Normalization does not significantly improve the correlation of absolute ADC with OS in HGG, suggesting that normalization is not necessary for clinical or research ADC analysis in HGG patients.

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The Lateral Femoral Cutaneous Nerve: Description of the Sensory Territory and a Novel Ultrasound-Guided Nerve Block Technique

Background and Objectives Nerve blockade of the lateral femoral cutaneous (LFC) nerve provides some analgesia after hip surgery. However, knowledge is lacking about the extent of the cutaneous area anesthetized by established LFC nerve block techniques, as well as the success rate of anesthetic coverage of various surgical incisions. Nerve block techniques that rely on ultrasonographic identification of the LFC nerve distal to the inguinal ligament can be technically challenging. Furthermore, the branching of the LFC nerve is variable, and it is unknown if proximal LFC nerve branches are anesthetized using the current techniques. The primary aim of this study was to investigate a novel ultrasound-guided LFC nerve block technique based on injection into the fat-filled flat tunnel (FFFT), which is a duplicature of the fascia lata between the sartorius and the tensor fasciae latae muscle, in order to assess the success rate of anesthetizing the proximal LFC nerve branches and covering of the different surgical incisions used for hip surgery. Methods First, a cadaveric study was conducted in order to identify an FFFT injection technique that would provide adequate injectate spread to the proximal LFC nerve branches. Second, a clinical study was conducted in a group of 20 healthy volunteers over 2 consecutive days. On trial day 1, successful complete anesthesia of the LFC nerve was defined by performing a suprainguinal fascia iliaca block bilaterally in each subject. On trial day 2, a triple-blind randomized controlled trial compared the effect of the novel ultrasound-guided LFC nerve block technique for bupivacaine versus placebo. The primary end point was the success rate of anesthesia of the proximal cutaneous area innervated by the LFC nerve for the FFFT injection with bupivacaine versus placebo. Results Adequate spread of injectate to the proximal LFC nerve branches in cadavers was obtained by injecting 10 mL with dynamic needle-tip tracking in the FFFT. Application of this technique in the randomized controlled trial provided anesthesia of the lateral thigh with a success rate of 95% (95% confidence interval, 73.9%–99.8%) for the active side and 0% for placebo (P

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Efficacy and Safety of Lidocaine Infusion Treatment for Neuropathic Pain: A Randomized, Double-Blind, and Placebo-Controlled Study

Background and Objectives Lidocaine infusion therapy (LIT) is an effective treatment for relieving neuropathic pain (NeP). However, it remains unclear whether pain relief can be sustained through repeated lidocaine infusions. This study aimed to determine whether repeated intravenous administration of low-dose lidocaine could provide prolonged pain relief in patients with specific NeP conditions. Methods This is a prospective, randomized, double-blind, placebo-controlled, parallel study. We compared the efficacy and safety of lidocaine infusions (3 mg/kg) in the LIT group and normal saline infusions in the control group once a week for 4 consecutive weeks in patients with postherpetic neuralgia or complex regional pain syndrome type II. The primary outcome was the difference in the percentage change in the 11-point numerical rating scale (NRS) pain score from baseline to after the final infusion. Secondary outcomes included pain scores during 4 weeks of follow-up and any complications. Results Forty-two patients completed this study protocol. The percentage reduction in NRS pain scores after the final infusion was significantly greater in the LIT group compared with the control group (P = 0.011). However, this pain reduction was not detectable at the 4-week follow-up. The difference in the percentage change in NRS pain scores was especially prominent in the LIT group after the third and fourth infusions. None of the study participants experienced serious complications from the treatment. Conclusions Lidocaine infusion therapy (3 mg/kg of lidocaine administered over 1 hour) provided effective short-term pain relief, which was substantially prominent after repeated infusions were administered to patients with refractory NeP. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02597257. Accepted for publication September 2, 2017. Address correspondence to: Jee Youn Moon, MD, PhD, FIPP, CIPS, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital College of Medicine, 110 Daehang-ro, Jongno-gu, Seoul 110-744, Korea (e-mail: jymoon0901@gmail.com). This research was supported by a grant (14172MFDS178) from Korean Ministry of Food and Drug Safety in 2014. The agency was not involved in conduct of this study or its submission. The authors declare no conflict of interest. Y.-C.K., A.M.C., and C.-S.L. contributed equally to this study. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Dexamethasone as an Adjuvant to Femoral Nerve Block in Children and Adolescents Undergoing Knee Arthroscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Background and Objectives Perineural dexamethasone has been demonstrated to extend postsurgical analgesia after peripheral nerve blockade in adults. The mechanism of action of dexamethasone as a regional anesthetic adjuvant is unclear as intravenous dexamethasone has been shown to have similar analgesic efficacy as perineural dexamethasone. The efficacy of perineural dexamethasone has not been previously explored in the pediatric population. Methods After obtaining informed consent, children (aged 10–18 years) presenting for arthroscopic knee surgery with a femoral nerve block were randomized to 1 of 3 groups: ropivacaine 0.5% and intramuscular saline (group R), ropivacaine 0.5% plus perineural dexamethasone 0.1 mg/kg (maximum 4 mg) and intramuscular saline (group D), and ropivacaine 0.5% and intramuscular dexamethasone 0.1 mg/kg (maximum 4 mg) (group M). The primary outcome was the number of doses of analgesic agents in the first 48 hours after hospital discharge. The number of doses was compared across study groups using Wilcoxon rank sum tests. Results Seventy-seven patients were enrolled in the study, of whom 4 were withdrawn because of additional surgical repair being performed, emergence delirium requiring unblinding, or loss to follow-up. The remaining 36 boys and 37 girls (aged 15 ± 2 years) included 23 patients randomized to group D, 23 patients randomized to group M, and 27 patients randomized to group R. The median number of pain medication doses within 48 hours of discharge was 2, 3, and 2 in groups D, M, and R, respectively. There were no significant differences in this outcome between groups D and M (difference in medians, 1; 95% confidence interval [CI] of difference in medians, −1 to 2; P = 0.475), groups D and R (difference in medians, 0; 95% CI of difference, −2 to 1; P = 0.821), or groups M and R (difference in medians, −1; 95% CI of difference, −2 to 1; P = 0.594). Other secondary outcomes, including time to first analgesic consumption after discharge, visual analog scale pain score, and subjective intensity of motor block, did not evince statistically significant differences among the study groups. Conclusions In the pediatric population, perineural or intramuscular dexamethasone did not improve analgesia after femoral nerve blockade for knee arthroscopy. Whether the observed lack of benefit reflects a true adult-pediatric difference or a limitation of the study could not be determined. Future pediatric studies are needed to evaluate dexamethasone for other block types and other types of surgery. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT01971645. Accepted for publication October 4, 2017. Address correspondence to: Giorgio Veneziano, MD, Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH 43205 (e-mail: Giorgio.Veneziano@Nationwidechildrens.org). This project was supported by The Clinical and Translational Intramural Funding Program (award grant number UL1TR001070), through the Research Institute at Nationwide Children's Hospital (Columbus, OH). The content is solely the responsibility of the authors and does not necessarily represent the official views of Nationwide Children's Hospital. This work was presented in part at moderated abstract presentations at the Society of Pediatric Pain Medicine's CCAS 2017 Annual Meeting on March 2 and the SPA-AAP Pediatric Anesthesiology 2017, on March 3, 2017, both in Austin, TX. The authors declare no conflict of interest. This study was registered with the Food and Drug Administration as an investigational new drug (IND 120188). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Evaluation of the tumor movement and the reproducibility of two different immobilization setups for image-guided stereotactic body radiotherapy of liver tumors

The purpose of this study is to evaluate the tumor movement and accuracy of patient immobilization in stereotactic body radiotherapy of liver tumors with low pressure foil or abdominal compression.

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HyperArc VMAT planning for single and multiple brain metastases stereotactic radiosurgery: a new treatment planning approach

The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT pl...

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Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control

Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Add...

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Chronic postsurgical pain following breast reconstruction: a commentary and critique

Abstract

In line with other major surgeries including breast cancer surgery (BCS), recent studies suggest a striking rate of chronic postsurgical pain (CPSP) following breast reconstruction. This commentary will critically examine evidence for the degree to which the prevalence of CPSP following breast reconstruction is directly attributable to reconstructive surgery. The discussion will trace similarities and distinctions between breast reconstruction and BCS in considering the risk for CPSP, and describe recent advances in the definition of CPSP, highlighting methodological limitations in the general investigation of CPSP, which also characterize the study of CPSP more specifically for breast reconstruction outcome. A convenience sample of relevant studies examining CPSP following breast reconstruction reveals inadequate evidence to support a serious concern for reconstruction-induced CPSP and further that these studies fail to adhere to recommended methodological standards to effectively isolate surgery as the etiology of persistent pain reported by women following reconstructive surgery. Suggestions for future exploration of problematic chronic pain after breast reconstruction are considered.

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Evaluation of the tumor movement and the reproducibility of two different immobilization setups for image-guided stereotactic body radiotherapy of liver tumors

The purpose of this study is to evaluate the tumor movement and accuracy of patient immobilization in stereotactic body radiotherapy of liver tumors with low pressure foil or abdominal compression.

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HyperArc VMAT planning for single and multiple brain metastases stereotactic radiosurgery: a new treatment planning approach

The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT pl...

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Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control

Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Add...

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Staphylococcal scalded skin syndrome in a 4-year-old child: a case report

Staphylococcal scalded skin syndrome is an exfoliating skin disease which primarily affects children. Differential diagnosis includes toxic epidermal necrolysis, staphylococcal scalded skin syndrome, epidermol...

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The differences on efficacy of oxaliplatin in locally advanced colon cancer between mucinous and nonmucinous adenocarcinoma

Abstract

Until now, it remains unclear how to best use the histological subtype in clinical practice. This study aimed to compare differences in the efficacy of postoperative chemotherapy among different histological subtypes of colon adenocarcinomas. Using the Surveillance, Epidemiology, and End Results-Medicare database, 51,200 patients with stage II or III primary colon carcinomas who underwent resection for curative intent between 1992 and 2008 were included. The survival benefit was evaluated using a Cox proportional hazards model, interaction analyses, and propensity score-matched techniques. There was no significant difference in survival for low-risk stage II mucinous adenocarcinoma (MA) or nonmucinous adenocarcinoma (NMA) between 5-FU and oxaliplatin-treated groups (P = 0.387 for MA, P = 0.629 for NMA). Patients with high-risk stage II NMA who received the oxaliplatin chemotherapy regimen had significantly improved cancer-specific survival (CSS) compared with the 5-FU group (P = 0.004), while those with MA saw no improvement (P = 0.690). For stage III tumors, patients with NMA who received the oxaliplatin chemotherapy regimen had significantly improved CSS compared with the 5-FU group (P < 0.001), while those with MA saw no improvement (P = 0.300). There were significant interactions between chemotherapy regimen and histological subtype. For patients with resected colon cancer who received 5-FU-based postoperative chemotherapy, oxaliplatin chemotherapy prolongs CSS for stage III and high-risk stage II NMA. Conversely, there was no similar improvement with addition of oxaliplatin for patients with stage III or stage II MA.

Until now, it remains unclear how to best use the histological subtype in clinical practice. For patients with resected colon cancer who received 5-FU-based postoperative chemotherapy, adding oxaliplatin can improve CSS for patients with stage III or high-risk stage II NMA. Conversely, there was no similar improvement for patients with stage III or high-risk stage II MA.

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Distinct predictive impact of FISH abnormality in proteasome inhibitors and immunomodulatory agents response: redefining high-risk multiple myeloma in Asian patients

Abstract

For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), and +1q21 in 40.8% (211/517). The presence of del(17p13), IgH rearrangement, and t(14;16) was associated with worse overall survival. Interestingly, however, the presence of t(4;14) conferred little prognostic impact. Treatment-specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation (autoSCT) was less effective in patients with del(17p13), t(14;16), and trisomy 1q21. Predictive values of del(17p13) and t(14;16) to bortezomib and autoSCT are seemingly universal, but predictive marker del(13q14) and del(9p21) for lenalidomide response appears ethnicity-specific. Thus, FISH profiles in MM treatment should be interpreted with regards to patient's ethnicity.

Treatment-specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation was less effective in patients with del(17p13), t(14;16), and trisomy 1q21.

http://ift.tt/2rOO4sh

Identification of a small-molecule ligand of β-arrestin1 as an inhibitor of stromal fibroblast cell migration accelerated by cancer cells

Abstract

Stromal fibroblasts, which occupy a major portion of the tumor microenvironment, play an important role in cancer metastasis. Thus, targeting of these fibroblasts activated by cancer cells (carcinoma-associated fibroblasts; CAFs) might aid in the improved treatment of cancer metastasis. NIH3T3 fibroblasts cocultured with MCF7 cells displayed enhanced migration compared to NIH3T3 fibroblasts cultured alone. We used this system to identify the small-molecule inhibitors responsible for their enhanced migration, a characteristic of CAFs. We selected β-arrestin1, which showed high expression in cocultured cells, as a molecular target for such inhibitors. Cofilin, a protein downstream of β-arrestin1, is activated/dephosphorylated in this condition. The small-molecule ligands of β-arrestin1 obtained by chemical array were then examined using a wound healing coculture assay. RKN5755 was identified as a selective inhibitor of activated fibroblasts. RKN5755 inhibited the enhanced migration of fibroblasts cocultured with cancer cells by binding to β-arrestin1 and interfering with β-arrestin1-mediated cofilin signaling pathways. Therefore, these results demonstrate the role of β-arrestin1 in the activation of fibroblasts and inhibiting this protein by small molecule inhibitor might be a potential therapeutic target for the stromal fibroblast activation (cancer–stroma interaction).

NIH3T3 fibroblasts cocultured with MCF7 cells displayed enhanced migration compared to NIH3T3 fibroblasts cultured alone. Using this system, we identified RKN5755, a selective inhibitor of activated fibroblasts. This small molecule binds to β-arrestin1 and interferes with β-arrestin1-mediated cofilin signaling pathways.

http://ift.tt/2Gwo4VF

Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis

Abstract

Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2014). Overall survival was analyzed using Kaplan–Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan–Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection.

The purpose of our study was to discuss whether the new N category (N0, N1, N2) or the 8th staging systems for PDAC is suitable for pNETs, and the results showed that the 8th staging systems for PDAC are more suitable for pNETs compared with the 8th staging systems for pNETs/ENETS.

http://ift.tt/2rQTeUw

Global named patient use program of afatinib in advanced non-small-cell lung carcinoma patients who progressed following prior therapies

Future Oncology, Ahead of Print.


http://ift.tt/2DXYP04

A case report and a literature review of primary retroperitoneal mucinous cystadenoma: the importance of imaging in diagnosis and management

Future Oncology, Ahead of Print.


http://ift.tt/2FsR7bB

The differences on efficacy of oxaliplatin in locally advanced colon cancer between mucinous and nonmucinous adenocarcinoma

Abstract

Until now, it remains unclear how to best use the histological subtype in clinical practice. This study aimed to compare differences in the efficacy of postoperative chemotherapy among different histological subtypes of colon adenocarcinomas. Using the Surveillance, Epidemiology, and End Results-Medicare database, 51,200 patients with stage II or III primary colon carcinomas who underwent resection for curative intent between 1992 and 2008 were included. The survival benefit was evaluated using a Cox proportional hazards model, interaction analyses, and propensity score-matched techniques. There was no significant difference in survival for low-risk stage II mucinous adenocarcinoma (MA) or nonmucinous adenocarcinoma (NMA) between 5-FU and oxaliplatin-treated groups (P = 0.387 for MA, P = 0.629 for NMA). Patients with high-risk stage II NMA who received the oxaliplatin chemotherapy regimen had significantly improved cancer-specific survival (CSS) compared with the 5-FU group (P = 0.004), while those with MA saw no improvement (P = 0.690). For stage III tumors, patients with NMA who received the oxaliplatin chemotherapy regimen had significantly improved CSS compared with the 5-FU group (P < 0.001), while those with MA saw no improvement (P = 0.300). There were significant interactions between chemotherapy regimen and histological subtype. For patients with resected colon cancer who received 5-FU-based postoperative chemotherapy, oxaliplatin chemotherapy prolongs CSS for stage III and high-risk stage II NMA. Conversely, there was no similar improvement with addition of oxaliplatin for patients with stage III or stage II MA.

Until now, it remains unclear how to best use the histological subtype in clinical practice. For patients with resected colon cancer who received 5-FU-based postoperative chemotherapy, adding oxaliplatin can improve CSS for patients with stage III or high-risk stage II NMA. Conversely, there was no similar improvement for patients with stage III or high-risk stage II MA.

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Distinct predictive impact of FISH abnormality in proteasome inhibitors and immunomodulatory agents response: redefining high-risk multiple myeloma in Asian patients

Abstract

For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), and +1q21 in 40.8% (211/517). The presence of del(17p13), IgH rearrangement, and t(14;16) was associated with worse overall survival. Interestingly, however, the presence of t(4;14) conferred little prognostic impact. Treatment-specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation (autoSCT) was less effective in patients with del(17p13), t(14;16), and trisomy 1q21. Predictive values of del(17p13) and t(14;16) to bortezomib and autoSCT are seemingly universal, but predictive marker del(13q14) and del(9p21) for lenalidomide response appears ethnicity-specific. Thus, FISH profiles in MM treatment should be interpreted with regards to patient's ethnicity.

Treatment-specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation was less effective in patients with del(17p13), t(14;16), and trisomy 1q21.

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Identification of a small-molecule ligand of β-arrestin1 as an inhibitor of stromal fibroblast cell migration accelerated by cancer cells

Abstract

Stromal fibroblasts, which occupy a major portion of the tumor microenvironment, play an important role in cancer metastasis. Thus, targeting of these fibroblasts activated by cancer cells (carcinoma-associated fibroblasts; CAFs) might aid in the improved treatment of cancer metastasis. NIH3T3 fibroblasts cocultured with MCF7 cells displayed enhanced migration compared to NIH3T3 fibroblasts cultured alone. We used this system to identify the small-molecule inhibitors responsible for their enhanced migration, a characteristic of CAFs. We selected β-arrestin1, which showed high expression in cocultured cells, as a molecular target for such inhibitors. Cofilin, a protein downstream of β-arrestin1, is activated/dephosphorylated in this condition. The small-molecule ligands of β-arrestin1 obtained by chemical array were then examined using a wound healing coculture assay. RKN5755 was identified as a selective inhibitor of activated fibroblasts. RKN5755 inhibited the enhanced migration of fibroblasts cocultured with cancer cells by binding to β-arrestin1 and interfering with β-arrestin1-mediated cofilin signaling pathways. Therefore, these results demonstrate the role of β-arrestin1 in the activation of fibroblasts and inhibiting this protein by small molecule inhibitor might be a potential therapeutic target for the stromal fibroblast activation (cancer–stroma interaction).

NIH3T3 fibroblasts cocultured with MCF7 cells displayed enhanced migration compared to NIH3T3 fibroblasts cultured alone. Using this system, we identified RKN5755, a selective inhibitor of activated fibroblasts. This small molecule binds to β-arrestin1 and interferes with β-arrestin1-mediated cofilin signaling pathways.

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Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis

Abstract

Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2014). Overall survival was analyzed using Kaplan–Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan–Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection.

The purpose of our study was to discuss whether the new N category (N0, N1, N2) or the 8th staging systems for PDAC is suitable for pNETs, and the results showed that the 8th staging systems for PDAC are more suitable for pNETs compared with the 8th staging systems for pNETs/ENETS.

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Global named patient use program of afatinib in advanced non-small-cell lung carcinoma patients who progressed following prior therapies

Future Oncology, Ahead of Print.


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A case report and a literature review of primary retroperitoneal mucinous cystadenoma: the importance of imaging in diagnosis and management

Future Oncology, Ahead of Print.


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It is time to move forward into the era of Theranostics

Abstract

Radionuclide therapy, which until 15 years ago included only a few approved therapies, is gaining importance in the treatment of various malignancies. The future of oncology will not be limited to surgery, chemo-, antibody therapies or external radiation; it will include targeted therapy with radionuclides, which will become the standard of care for a variety of malignant diseases in combination or as an alternative to other therapies. Therefore there is a need to train Nuclear Oncologists, who are able to approach oncological diseases, promote development of radiopharmacy, understand the biology of radionuclide treatment, apply radionuclide treatments and be able to use molecular imaging such as PET/CT and SPECT/CT for treatment planning and dosimetry.

http://ift.tt/2DYIlog

It is time to move forward into the era of Theranostics

Abstract

Radionuclide therapy, which until 15 years ago included only a few approved therapies, is gaining importance in the treatment of various malignancies. The future of oncology will not be limited to surgery, chemo-, antibody therapies or external radiation; it will include targeted therapy with radionuclides, which will become the standard of care for a variety of malignant diseases in combination or as an alternative to other therapies. Therefore there is a need to train Nuclear Oncologists, who are able to approach oncological diseases, promote development of radiopharmacy, understand the biology of radionuclide treatment, apply radionuclide treatments and be able to use molecular imaging such as PET/CT and SPECT/CT for treatment planning and dosimetry.

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Pathological response in a triple negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification

Purpose: Triple-negative breast cancer (TNBC) requires the identification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of TNBC patients treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: TNBC patients were accrued in a non-randomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for 6 cycles. Response was evaluated in terms of pathological complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans et al. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of 7 DNA damage repair genes was conducted. Results: 94 out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was: 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (p=0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%) and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2 and 30% were M. Conclusions: TNBCtype-4 is associated with a significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT respectively.

http://ift.tt/2DXr2Eh

Pathological response in a triple negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification

Purpose: Triple-negative breast cancer (TNBC) requires the identification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of TNBC patients treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: TNBC patients were accrued in a non-randomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for 6 cycles. Response was evaluated in terms of pathological complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans et al. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of 7 DNA damage repair genes was conducted. Results: 94 out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was: 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (p=0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%) and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2 and 30% were M. Conclusions: TNBCtype-4 is associated with a significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT respectively.

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Celgene Targets Blood Cancers with Major Buys [News in Brief]

Lenalidomide maker diversifies its CAR T portfolio and acquires a near-market JAK inhibitor with Juno, Impact deals.

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miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3

Hepatitis B virus (HBV) plays a critical role in the tumorigenic behavior of human hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to participate in HCC development via the regulation of ...

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Intraosseous papillary intralymphatic angioendothelioma (PILA): one new case and review of the literature

Abstract

Background

Papillary intralymphatic angioendothelioma (PILA) is a locally aggressive, rarely metastasizing vascular tumor, generally occurring in the soft tissues, with less than 40 cases described in the literature and only three cases reported in bone.

Case presentation

We describe the case of a 51-year-old male with an intraosseous PILA of the proximal edge of his left clavicle and two other lesions evident on imaging. The patient was treated with marginal resection of the clavicle lesion but was lost to follow-up 1 month after surgery.

Conclusions

PILA can also occur in bone, albeit very rarely, and has to be considered in the differential diagnosis of vascular bone tumors.

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Intraosseous papillary intralymphatic angioendothelioma (PILA): one new case and review of the literature

Abstract

Background

Papillary intralymphatic angioendothelioma (PILA) is a locally aggressive, rarely metastasizing vascular tumor, generally occurring in the soft tissues, with less than 40 cases described in the literature and only three cases reported in bone.

Case presentation

We describe the case of a 51-year-old male with an intraosseous PILA of the proximal edge of his left clavicle and two other lesions evident on imaging. The patient was treated with marginal resection of the clavicle lesion but was lost to follow-up 1 month after surgery.

Conclusions

PILA can also occur in bone, albeit very rarely, and has to be considered in the differential diagnosis of vascular bone tumors.

http://ift.tt/2BDNtZT

Olaparib Approved for Treating Some Breast Cancers with BRCA Gene Mutations

The drug olaparib (Lynparza®) is the first treatment approved by the Food and Drug Administration for patients with metastatic breast cancer who have inherited mutations in the BRCA1 or BRCA2 genes.

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Olaparib Approved for Treating Some Breast Cancers with BRCA Gene Mutations

The drug olaparib (Lynparza®) is the first treatment approved by the Food and Drug Administration for patients with metastatic breast cancer who have inherited mutations in the BRCA1 or BRCA2 genes.

http://ift.tt/2BBO921

Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer

Abstract

Thyroid hormone status has long been implicated in cancer development. Here we investigated the role of thyroxine (T₄) in colorectal cancer cell lines HCT 116 (APC wild type) and HT-29 (APC mutant), as well as the primary cultures of cancer cells derived from patients. Cell proliferation was evaluated with standard assay and proliferation marker expression. β-Catenin activation was examined according to nuclear β-catenin accumulation and β-catenin target gene expression. The results showed that T₄ increased colorectal cancer cell proliferation while cell number and viability were elevated by T₄ in both established cell lines and primary cells. Moreover, the transcriptions of proliferative genes PCNA, CCND1, and c-Myc were enhanced by T₄ in the primary cells. T₄ induced nuclear β-catenin accumulation, as well as high cyclin D1 and c-Myc levels compared to the untreated cells. In addition, the β-catenin-directed transactivation of CCND1 and c-Myc promoters was also upregulated by T₄. CTNNB1 transcription was raised by T₄ in HCT 116, but not in HT-29, while the boosted β-catenin levels were observed in both. Lastly, the T₄-mediated gene expression could be averted by the knockdown of β-catenin. These results suggested that T₄ promotes β-catenin activation and cell proliferation in colorectal cancer, indicating that an applicable therapeutic strategy should be considered.

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Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer

Abstract

Thyroid hormone status has long been implicated in cancer development. Here we investigated the role of thyroxine (T₄) in colorectal cancer cell lines HCT 116 (APC wild type) and HT-29 (APC mutant), as well as the primary cultures of cancer cells derived from patients. Cell proliferation was evaluated with standard assay and proliferation marker expression. β-Catenin activation was examined according to nuclear β-catenin accumulation and β-catenin target gene expression. The results showed that T₄ increased colorectal cancer cell proliferation while cell number and viability were elevated by T₄ in both established cell lines and primary cells. Moreover, the transcriptions of proliferative genes PCNA, CCND1, and c-Myc were enhanced by T₄ in the primary cells. T₄ induced nuclear β-catenin accumulation, as well as high cyclin D1 and c-Myc levels compared to the untreated cells. In addition, the β-catenin-directed transactivation of CCND1 and c-Myc promoters was also upregulated by T₄. CTNNB1 transcription was raised by T₄ in HCT 116, but not in HT-29, while the boosted β-catenin levels were observed in both. Lastly, the T₄-mediated gene expression could be averted by the knockdown of β-catenin. These results suggested that T₄ promotes β-catenin activation and cell proliferation in colorectal cancer, indicating that an applicable therapeutic strategy should be considered.

http://ift.tt/2DUOvpM

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Elderly: Is It Reasonable? A Meta-Analysis

Abstract

Background

Whether cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is safe and worthwhile for elderly patients remains unclear. This meta-analysis of outcomes after CRS plus HIPEC for the elderly aimed to generate a higher level of evidence and precise indications for these patients.

Methods

A systematic literature search for studies reporting postoperative outcomes after CRS plus HIPEC for elderly patients was performed in the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Knowledge Conference Proceedings Citation Index-Science, and Google Scholar databases. The included studies evaluated the overall 30-day postoperative morbidity, 90-day postoperative mortality, grade 3 or higher postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay.

Results

The inclusion criteria were met by 13 retrospective studies involving 2544 patients. Considering only comparative studies, the 90-day postoperative mortality was significantly increased for elderly patients [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27–0.88; I ² = 79%]. The 30-day grade 3 or higher postoperative morbidity was increased in the patients 70 years of age or older (14.5%; 95% CI 8.1–24.4 vs. 32.3%; 95% CI 22.4–44.0%; p = 0.004; I ² = 85%). The overall 30-day postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay were not affected by age.

Conclusions

Treatment of the elderly with CRS plus HIPEC was associated with increased severe postoperative morbidity and mortality. However, these conclusions should be weighted given the existence of major biases in the included studies. Age alone probably would not be a formal contraindication, but frailty should be taken into account. Further prospective studies are needed.

http://ift.tt/2Ep7mXT

Perioperative Risk Calculator Predicts Long-Term Oncologic Outcome for Patients with Esophageal Carcinoma

Abstract

Background

Few risk models have been provided to predict long-term prognosis after esophagectomy. This study investigated the reliability of a risk calculator as well as classification and regression trees analysis for predicting long-term prognosis after esophagectomy for esophageal cancer.

Methods

The study enrolled 438 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between July 2000 and June 2016. Patients who underwent R0 or R1 resection or esophagectomy with combined resection of other organs were included. The authors investigated the usefulness of a risk model for 30-day mortality and operative mortality described in their previous report for predicting long-term prognosis after esophagectomy.

Results

The 438 patients (377 men and 61 women) in this study had a 5-year overall survival (OS) rate of 62.8% and a disease-free survival rate of 54.3%. The OS was higher for the patients with 30-day mortality risk model values lower than 0.675% than for those with values higher than 0.675% (p < 0.001). The cutoff values for prediction were shown to be significant risk factors in the multivariate analysis. The risk calculator was validated by comparing the cutoff values with Harrell's C-index values of clinical stage. For overall risk, the C-index of operative mortality was 0.697, and the C-index of cStage was 0.671.

Conclusions

The risk calculator was useful for predicting recurrence and death after esophagectomy. Furthermore, because the C-index of the risk model for operative mortality was higher than for clinical tumor-node-metastasis stage, this risk-scoring system may be more useful clinically.

http://ift.tt/2DISVMU

PCI is Not Predictive of Survival After Complete CRS/HIPEC in Peritoneal Dissemination from High-Grade Appendiceal Primaries

Abstract

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival.

Methods

Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction.

Results

Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0–36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error [SE] 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (p = 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (p = 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (p = 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21.

Conclusions

The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.

http://ift.tt/2EkK6tT

Anterolateral Thigh Flap Combined with Reconstruction Plate Versus Double Free Flaps for Composite Mandibular Reconstruction: A Propensity Score-Matched Study

Abstract

Objective

This study was designed to examine the comparative effectiveness of oromandibular defect reconstruction via anterolateral thigh flap and bridging plate (ALT only) versus simultaneous soft tissue and vascularized bone flap (DFF), with regards to long-term plate exposure and complications.

Methods

A propensity score-matched analysis of patients with an oncologic head and neck defect who underwent microvascular reconstruction was performed. Two surgical groups, i.e., ALT only and DFF, were created. Incidence and subsequent management strategies for postoperative plate exposure were evaluated along with complications, overall survival, and postoperative quality of life (QoL).

Results

Sixty-two patients were 1:1 propensity matched (31 per group). The DFF group had a significantly larger soft tissue and bone defect than the single-flap group. The 5-year probability of not having a plate exposure was 45.5 and 47.4% for the double-flaps and single-flap groups, respectively (p = 0.186). The ALT-only group had a significantly higher rate of wound infections (38.7% vs. 12.9%, p = 0.02). The incidence of flap loss, reexploration, inpatient mortality, plate fracture, medical complications, and overall survival were not significantly different. Although mean score for pain was significantly worse in the ALT-only group (75.2 vs. 88.5, p < 0.001), the remainder of our QoL assessments (cosmesis, swallow, employment, and speech) were comparable.

Conclusions

The utilization of an ALT with plate strategy is associated with competitive rates of plate exposure and overall survival relative to DFF but higher wound infections and long-term pain. These results have considerable salience for patient-counseling regarding expectations for functional and clinical outcomes.

http://ift.tt/2DIGOzC

Core Body Temperature but Not Intraabdominal Pressure Predicts Postoperative Complications Following Closed-System Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Administration

Abstract

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications.

Patients and Methods

Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44 °C, and mean perfusate temperature was 42 °C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2–10 mmHg, n = 28), target IAP group (10–20 mmHg, n = 71), and high IAP group (20–34 mmHg, n = 16) as well as with CBT as a continuous variable.

Results

115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p = 0.035).

Conclusions

IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.

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Histologic Predictors of Recurrence in Mucinous Appendiceal Tumors with Peritoneal Dissemination after HIPEC

Abstract

Background

Mucinous appendiceal tumors (MAT) are rare neoplasms that can metastasize to the peritoneum and often are treated with cytoreductive surgery (CRS) and HIPEC. Pathologic classification and outcomes vary, but standardized histologic definitions are emerging. We sought to evaluate outcomes in this disease after CRS/HIPEC using standardized pathologic criteria.

Method

Outcomes of MAT with peritoneal metastases (PM) after CRS/HIPEC from 2007 to 2015 were reviewed at our institution. Standardized histologic categories per WHO and consensus definitions were used: low-grade appendiceal mucinous neoplasm (LAMN), low-grade adenocarcinoma (LGAC), or high-grade adenocarcinoma (HGAC) primary tumors; and acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), or high-grade mucinous carcinoma peritonei (HGMCP) peritoneal metastases. Cox proportional hazards model was used identify predictors of progression-free survival (PFS) by univariate and multivariate analyses.

Results

A total of 183 patients undergoing 197 CRS/HIPECs were included. Among 75 patients with primary histology review, there were 33 (44.0%) LAMNs, 28 (37.3%) LGACs, and 14 (18.7%) HGACs. Peritoneal histology was benign in 6 (3.0%), AM in 33 (16.8%), LGMCP in 114 (57.9%), and HGMCP in 44 (22.3%). PFS was not reached for AM, 34.3 months for LGMCP, and 16.8 months for HGMCP (p < 0.001). Peritoneal histology predicted PFS on multivariate analysis (hazard ratio 9.82 and 24.60 for LGMCP and HGMCP, respectively, vs. AM, p < 0.001). Among the LGMCP group, CEA and completeness of cytoreduction (CC score) predicted PFS on multivariate analysis.

Conclusions

Standardized peritoneal histology in patients with PM from MAT predicts PFS and patients with low-grade histology can be further discriminated by CEA and CC score.

http://ift.tt/2DKxBGR

Decreased Use of Sphincter-Preserving Procedures Among African Americans with Rectal Cancer

Abstract

Background

Improved multimodality rectal cancer treatment has increased the use of sphincter-preserving surgery. This study sought to determine whether African American (AA) patients with rectal cancer receive sphincter-preserving surgery at the same rate as non-AA patients.

Methods

The study used the Nationwide Inpatient Sample for years 1998–2012 to compare AA and non-AA patients with rectal cancer undergoing low anterior resection or abdominoperineal resection. The logistic regression model was used to adjust for age, gender, admission type, Elixhauser comorbidity index, and hospital factors such as size, location (urban vs.rural), teaching status, and procedure volume.

Results

The search identified 22,697 patients, 1600 of whom were identified as AA. After adjustment for age and gender, the analysis showed that AA patients were less likely to undergo sphincter-preserving surgery than non-AA patients [odds ratio (OR) 0.70; 95% confidence interval (CI) 0.63–0.78; p < 0.0001). After further adjustment for the Elixhauser comorbidity index, admission type, hospital-specific factors, and insurance status, the analysis showed that AA patients still were less likely to undergo sphincter-preserving surgery (OR 0.78; 95% CI 0.70–0.87; p < 0.0001). Although the proportion of non-AA patients undergoing sphincter-preserving surgery increased during the study period (p = 0.0003), this trend was not significant for the AA patients (p = 0.13).

Conclusion

In this data analysis, the AA patients with rectal cancer had lower rates of sphincter-preserving surgery than the non-AA patients, even after adjustment for patient- and hospital-specific factors. Further work is required to elucidate why. Eliminating racial disparities in rectal cancer treatment should continue to be a priority for the surgical community.

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Challenges Staging Neuroendocrine Tumors of the Pancreas, Jejunum and Ileum, and Appendix

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Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Elderly: Is It Reasonable? A Meta-Analysis

Abstract

Background

Whether cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is safe and worthwhile for elderly patients remains unclear. This meta-analysis of outcomes after CRS plus HIPEC for the elderly aimed to generate a higher level of evidence and precise indications for these patients.

Methods

A systematic literature search for studies reporting postoperative outcomes after CRS plus HIPEC for elderly patients was performed in the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Knowledge Conference Proceedings Citation Index-Science, and Google Scholar databases. The included studies evaluated the overall 30-day postoperative morbidity, 90-day postoperative mortality, grade 3 or higher postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay.

Results

The inclusion criteria were met by 13 retrospective studies involving 2544 patients. Considering only comparative studies, the 90-day postoperative mortality was significantly increased for elderly patients [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27–0.88; I ² = 79%]. The 30-day grade 3 or higher postoperative morbidity was increased in the patients 70 years of age or older (14.5%; 95% CI 8.1–24.4 vs. 32.3%; 95% CI 22.4–44.0%; p = 0.004; I ² = 85%). The overall 30-day postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay were not affected by age.

Conclusions

Treatment of the elderly with CRS plus HIPEC was associated with increased severe postoperative morbidity and mortality. However, these conclusions should be weighted given the existence of major biases in the included studies. Age alone probably would not be a formal contraindication, but frailty should be taken into account. Further prospective studies are needed.

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Perioperative Risk Calculator Predicts Long-Term Oncologic Outcome for Patients with Esophageal Carcinoma

Abstract

Background

Few risk models have been provided to predict long-term prognosis after esophagectomy. This study investigated the reliability of a risk calculator as well as classification and regression trees analysis for predicting long-term prognosis after esophagectomy for esophageal cancer.

Methods

The study enrolled 438 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between July 2000 and June 2016. Patients who underwent R0 or R1 resection or esophagectomy with combined resection of other organs were included. The authors investigated the usefulness of a risk model for 30-day mortality and operative mortality described in their previous report for predicting long-term prognosis after esophagectomy.

Results

The 438 patients (377 men and 61 women) in this study had a 5-year overall survival (OS) rate of 62.8% and a disease-free survival rate of 54.3%. The OS was higher for the patients with 30-day mortality risk model values lower than 0.675% than for those with values higher than 0.675% (p < 0.001). The cutoff values for prediction were shown to be significant risk factors in the multivariate analysis. The risk calculator was validated by comparing the cutoff values with Harrell's C-index values of clinical stage. For overall risk, the C-index of operative mortality was 0.697, and the C-index of cStage was 0.671.

Conclusions

The risk calculator was useful for predicting recurrence and death after esophagectomy. Furthermore, because the C-index of the risk model for operative mortality was higher than for clinical tumor-node-metastasis stage, this risk-scoring system may be more useful clinically.

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PCI is Not Predictive of Survival After Complete CRS/HIPEC in Peritoneal Dissemination from High-Grade Appendiceal Primaries

Abstract

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival.

Methods

Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction.

Results

Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0–36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error [SE] 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (p = 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (p = 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (p = 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21.

Conclusions

The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.

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Anterolateral Thigh Flap Combined with Reconstruction Plate Versus Double Free Flaps for Composite Mandibular Reconstruction: A Propensity Score-Matched Study

Abstract

Objective

This study was designed to examine the comparative effectiveness of oromandibular defect reconstruction via anterolateral thigh flap and bridging plate (ALT only) versus simultaneous soft tissue and vascularized bone flap (DFF), with regards to long-term plate exposure and complications.

Methods

A propensity score-matched analysis of patients with an oncologic head and neck defect who underwent microvascular reconstruction was performed. Two surgical groups, i.e., ALT only and DFF, were created. Incidence and subsequent management strategies for postoperative plate exposure were evaluated along with complications, overall survival, and postoperative quality of life (QoL).

Results

Sixty-two patients were 1:1 propensity matched (31 per group). The DFF group had a significantly larger soft tissue and bone defect than the single-flap group. The 5-year probability of not having a plate exposure was 45.5 and 47.4% for the double-flaps and single-flap groups, respectively (p = 0.186). The ALT-only group had a significantly higher rate of wound infections (38.7% vs. 12.9%, p = 0.02). The incidence of flap loss, reexploration, inpatient mortality, plate fracture, medical complications, and overall survival were not significantly different. Although mean score for pain was significantly worse in the ALT-only group (75.2 vs. 88.5, p < 0.001), the remainder of our QoL assessments (cosmesis, swallow, employment, and speech) were comparable.

Conclusions

The utilization of an ALT with plate strategy is associated with competitive rates of plate exposure and overall survival relative to DFF but higher wound infections and long-term pain. These results have considerable salience for patient-counseling regarding expectations for functional and clinical outcomes.

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Core Body Temperature but Not Intraabdominal Pressure Predicts Postoperative Complications Following Closed-System Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Administration

Abstract

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications.

Patients and Methods

Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44 °C, and mean perfusate temperature was 42 °C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2–10 mmHg, n = 28), target IAP group (10–20 mmHg, n = 71), and high IAP group (20–34 mmHg, n = 16) as well as with CBT as a continuous variable.

Results

115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p = 0.035).

Conclusions

IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.

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Histologic Predictors of Recurrence in Mucinous Appendiceal Tumors with Peritoneal Dissemination after HIPEC

Abstract

Background

Mucinous appendiceal tumors (MAT) are rare neoplasms that can metastasize to the peritoneum and often are treated with cytoreductive surgery (CRS) and HIPEC. Pathologic classification and outcomes vary, but standardized histologic definitions are emerging. We sought to evaluate outcomes in this disease after CRS/HIPEC using standardized pathologic criteria.

Method

Outcomes of MAT with peritoneal metastases (PM) after CRS/HIPEC from 2007 to 2015 were reviewed at our institution. Standardized histologic categories per WHO and consensus definitions were used: low-grade appendiceal mucinous neoplasm (LAMN), low-grade adenocarcinoma (LGAC), or high-grade adenocarcinoma (HGAC) primary tumors; and acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), or high-grade mucinous carcinoma peritonei (HGMCP) peritoneal metastases. Cox proportional hazards model was used identify predictors of progression-free survival (PFS) by univariate and multivariate analyses.

Results

A total of 183 patients undergoing 197 CRS/HIPECs were included. Among 75 patients with primary histology review, there were 33 (44.0%) LAMNs, 28 (37.3%) LGACs, and 14 (18.7%) HGACs. Peritoneal histology was benign in 6 (3.0%), AM in 33 (16.8%), LGMCP in 114 (57.9%), and HGMCP in 44 (22.3%). PFS was not reached for AM, 34.3 months for LGMCP, and 16.8 months for HGMCP (p < 0.001). Peritoneal histology predicted PFS on multivariate analysis (hazard ratio 9.82 and 24.60 for LGMCP and HGMCP, respectively, vs. AM, p < 0.001). Among the LGMCP group, CEA and completeness of cytoreduction (CC score) predicted PFS on multivariate analysis.

Conclusions

Standardized peritoneal histology in patients with PM from MAT predicts PFS and patients with low-grade histology can be further discriminated by CEA and CC score.

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Decreased Use of Sphincter-Preserving Procedures Among African Americans with Rectal Cancer

Abstract

Background

Improved multimodality rectal cancer treatment has increased the use of sphincter-preserving surgery. This study sought to determine whether African American (AA) patients with rectal cancer receive sphincter-preserving surgery at the same rate as non-AA patients.

Methods

The study used the Nationwide Inpatient Sample for years 1998–2012 to compare AA and non-AA patients with rectal cancer undergoing low anterior resection or abdominoperineal resection. The logistic regression model was used to adjust for age, gender, admission type, Elixhauser comorbidity index, and hospital factors such as size, location (urban vs.rural), teaching status, and procedure volume.

Results

The search identified 22,697 patients, 1600 of whom were identified as AA. After adjustment for age and gender, the analysis showed that AA patients were less likely to undergo sphincter-preserving surgery than non-AA patients [odds ratio (OR) 0.70; 95% confidence interval (CI) 0.63–0.78; p < 0.0001). After further adjustment for the Elixhauser comorbidity index, admission type, hospital-specific factors, and insurance status, the analysis showed that AA patients still were less likely to undergo sphincter-preserving surgery (OR 0.78; 95% CI 0.70–0.87; p < 0.0001). Although the proportion of non-AA patients undergoing sphincter-preserving surgery increased during the study period (p = 0.0003), this trend was not significant for the AA patients (p = 0.13).

Conclusion

In this data analysis, the AA patients with rectal cancer had lower rates of sphincter-preserving surgery than the non-AA patients, even after adjustment for patient- and hospital-specific factors. Further work is required to elucidate why. Eliminating racial disparities in rectal cancer treatment should continue to be a priority for the surgical community.

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Challenges Staging Neuroendocrine Tumors of the Pancreas, Jejunum and Ileum, and Appendix

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Lymph drainage of the upper limb and mammary region to the axilla: anatomical study in stillborns

Abstract

Purpose

We studied the lymphatic drainage of the upper limb and mammary region directing to the axilla to investigate whether independent pathways can be observed or whether anastomoses and shared drainage occur between them. This analysis aimed to assess the safety of axillary reverse mapping (ARM) in breast cancer treatment and to understand the development of lymphedema after sentinel lymph node biopsy (SLNB) alone.

Methods

Seven unfixed stillborn fetuses were injected with a modified Gerota mass in the peri-areolar area, palm and dorsum of the hands, formalin fixed, and then submerged in 10% hydrogen peroxide solution. Microsurgical dissection was then performed on the subcutaneous cellular tissue of the upper limb, axillary region, and anterior thorax to expose the lymphatic vessels and lymph nodes.

Results

The dye injected into the upper limb reached either the lateral axillary group, known to be exclusively responsible for upper limb drainage, or the anterior group, which is typically related to breast drainage. There was great proximity among the pathways and lymph nodes. Communicating lymphatic vessels among these groups of lymph nodes were also found in all studied cases.

Discussion

Lymphedema remains a challenging morbidity in breast cancer treatment. ARM and SLNB aim to avoid unnecessary damage to the lymphatic drainage of the upper limb. However, our anatomical study suggests that ARM may have potential oncological risks because preserved lymph nodes may harbor malignant cells due their proximity, overlapping drainage pathways, and connecting lymph vessels among lymph nodes.

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Cancers, Vol. 10, Pages 36: Targeted Therapies for Pancreatic Cancer

Cancers, Vol. 10, Pages 36: Targeted Therapies for Pancreatic Cancer

Cancers doi: 10.3390/cancers10020036

Authors: Idoroenyi Amanam Vincent Chung

Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies.

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Cancers, Vol. 10, Pages 37: Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma

Cancers, Vol. 10, Pages 37: Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma

Cancers doi: 10.3390/cancers10020037

Authors: Masa Bosnjak Tanja Jesenko Urska Kamensek Gregor Sersa Jaka Lavrencak Loree Heller Maja Cemazar

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were determined. GET of all three plasmids caused significant growth delay in melanoma tumors; nevertheless, the effect of pVAX1 was significantly greater than pControl. While DNA sensors in vivo were not upregulated significantly, cytokines IFN β and TNF α were upregulated after GET of pVAX1. In vitro, the mRNAs of some cytosolic DNA sensors were overexpressed after GET; however, with no significant difference among the three plasmids. In summary, although differences in antitumor effects were observed among control plasmids in vivo, no differences in cellular responses to plasmid GET were detected in tumor cells in vitro. Thus, the tumor microenvironment as well as some plasmid properties are most probably responsible for the antitumor effectiveness.

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Cancers, Vol. 10, Pages 36: Targeted Therapies for Pancreatic Cancer

Cancers, Vol. 10, Pages 36: Targeted Therapies for Pancreatic Cancer

Cancers doi: 10.3390/cancers10020036

Authors: Idoroenyi Amanam Vincent Chung

Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies.

http://ift.tt/2DIOTUO

Cancers, Vol. 10, Pages 37: Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma

Cancers, Vol. 10, Pages 37: Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma

Cancers doi: 10.3390/cancers10020037

Authors: Masa Bosnjak Tanja Jesenko Urska Kamensek Gregor Sersa Jaka Lavrencak Loree Heller Maja Cemazar

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were determined. GET of all three plasmids caused significant growth delay in melanoma tumors; nevertheless, the effect of pVAX1 was significantly greater than pControl. While DNA sensors in vivo were not upregulated significantly, cytokines IFN β and TNF α were upregulated after GET of pVAX1. In vitro, the mRNAs of some cytosolic DNA sensors were overexpressed after GET; however, with no significant difference among the three plasmids. In summary, although differences in antitumor effects were observed among control plasmids in vivo, no differences in cellular responses to plasmid GET were detected in tumor cells in vitro. Thus, the tumor microenvironment as well as some plasmid properties are most probably responsible for the antitumor effectiveness.

http://ift.tt/2El9n7i