Tumor necrosis and clinical outcomes following neoadjuvant therapy in soft tissue sarcoma: A systematic review and meta-analysis

Publication date: Available online 19 May 2018
Source:Cancer Treatment Reviews
Author(s): Samer Salah, Jeremy Lewin, Eitan Amir, Albiruni Abdul Razak
BackgroundThe prognostic role of tumor necrosis following neoadjuvant therapy is established in bone sarcomas but remains unclear in soft tissue sarcomas (STS).MethodsWe searched MEDLINE, MEDLINE in progress, EMBASE and Cochrane to identify studies that investigated neoadjuvant therapy in STS. Studies were required to report survival data based on extent of necrosis, or provided individual patient data allowing estimation thereof. Hazard ratios (HR) for relapse-free (RFS) and overall survival (OS) and odds ratios (OR) for recurrence at 3 years and for death at 5 years were pooled in a random effect meta-analysis. Associations between patient characteristics and attainment of ≥90% necrosis were explored.Results21 studies comprising 1663 patients were included. Extremity tumors were most common (n=1554; 93%). Induction regimens included chemotherapy with radiotherapy (n=924; 56%), chemotherapy alone (n=412; 25%), radiotherapy alone (n=78; 5%), isolated limb perfusion (ILP) (n=231; 14%), and targeted therapy/radiotherapy (n=18; 1%). Patients with < 90% necrosis had higher hazard of recurrence (hazard ratio [HR] 1.47; 95% CI: 1.06-2.04; p = 0.02) and death (HR 1.86; 95% CI: 1.41-2.46; p < 0.001). Risk of recurrence at 3 years (OR=3.35; 95% CI: 2.27-4.92; p < 0.001) and of death at 5 years (OR 2.60; 95% CI: 1.59-4.26; p < 0.001) were similarly increased. Compared to other modalities, ILP was associated with higher odds of achieving ≥90% necrosis (OR 12.1; 95% CI: 3.69-39.88; p < 0.001).ConclusionTumour necrosis < 90% following neoadjuvant therapy is associated with increased recurrence risk and inferior OS in patients with STS.



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Cytoreductive Surgery in Combination with HIPEC in the Treatment of Peritoneal Sarcomatosis

Abstract

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal carcinomatosis, but it has been debated for peritoneal sarcomatosis. The purpose of the study is the presentation of perioperative and long-term results of CRS and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal sarcomatosis. Retrospective study in a prospectively maintained database of 20 patients that underwent 29 CRS + HIPEC for peritoneal sarcomatosis. Clinical and histopathologic variables were correlated to survival. Complete cytoreduction was possible in 86.2% of the cases. The hospital mortality and morbidity rate were 0 and 20.7%, respectively. The median follow-up was 26 months, and recurrence was recorded in 20 cases (69%). The median and 5-year survival was 55 ± 13 (34–58) months and 43%, respectively. Prior surgical score (PSS) was the single variable related to survival (p = 0.018). The histologic subtype of the tumor was related to recurrence (p < 0.001). CRS and HIPEC in peritoneal sarcomatosis may offer a survival benefit in selected patients with low hospital mortality. The variety of histologic types of sarcomatosis has not made possible the identification of subgroups of patients that may be offered significant benefit by CRS and HIPEC. Further studies are required.

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Different Presentations of Five Rare Cases of Sclerosing Stromal Tumor of the Ovary

Abstract

A rare subtype of preceding neoplasm of ovary is sclerosing stromal cell tumor with few presented cases in the literature. In these case series, we describe five cases of ovarian sclerosing stromal cell tumor with different presentations in our department. Interestingly, one of our cases had elevated alfa-fetoprotein.

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Re-irradiation in gynecological cancers, present experiences and future hopes

Abstract

Objective

Treatment of recurrent diseases in patients with cervical or endometrial cancers after primary treatment by radiotherapy is challenging due to limitations of treatment options and success rates. Results are variable with contrasting outcomes and toxicities.

Methods

The authors reviewed all recent evidences and summarized the recent series of studies along with recent advancements and future possibilities.

Results

Surgical options were traditionally limited to extensive resections such as pelvic exenteration with or without intraoperative radiotherapy (IORT) or radical radiotherapy. IORT can be used as an adjunct to surgery in recurrent malignancies with positive margins. Recent interstitial brachytherapy (ISBT) studies for central recurrences have demonstrated a moderate 2 to 3 years local control of ~ 50%. Stereotactic body radiotherapy (SBRT) has also emerged as an attractive and apparently viable alternative, especially in treating relapsed nodes and pelvic sidewall disease, achieving 1- and 2-year local control rates of about 80 and 50%, respectively.

Conclusion

The results of salvage re irradiation are reasonable. More upcoming evidences and ongoing technological innovations will guide us in more effective retreatment and addition to life in this group of patients.

https://ift.tt/2Gz27UO

Bizarre multilobated myeloma cells mimicking megakaryocytes

Publication date: Available online 19 May 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sunil Pasricha, Neha Singh, Ajit Panaych, Anurag Mehta




https://ift.tt/2IwdK0x

Current Frontline Endocrine Treatment Options for Women with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced-Stage Breast Cancer

Publication date: Available online 19 May 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Hikmat N. Abdel-Razeq
Despite the recent advances in breast cancer early detection and awareness, a significant portion of patients present with an advanced-stage disease and more patients will progress to stage IV despite adequate treatment of their initial early-stage disease. Hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor-2 (HER2)-negative subtype is the commonest among all breast cancer subtypes. The management of the advanced-stage disease of this subtype has evolved significantly over the past few years. The emergence of estrogen receptor down regulators (fulvestrant), mTOR-inhibitors and the recent introduction of CDK4/6 inhibitors, like palbociclib, abemaciclib and ribociclib, has resulted in a significant and a historical improvement in treatment outcomes.In this paper, we review many of the recently reported clinical trials that led to the approval of these new drugs in the first-line settings, along with the current international guidelines.



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Concurrence of symmetrical peripheral gangrene and venous limb gangrene following polytrauma: a case report

Symmetrical peripheral gangrene is characterized as acral (distal extremity) ischemic limb injury affecting two or more extremities, without large vessel obstruction, typically in a symmetrical fashion. Risk f...

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Development of a Novel Self-administered Cognitive Assessment Tool and Normative Data for Older Adults

Background: Preexisting cognitive impairment in surgical patients is one of the leading risk factors for adverse cognitive outcomes such as postoperative delirium and postoperative cognitive dysfunction. We developed a self-administered tablet computer application intended to assess the individual risk for adverse postoperative cognitive outcomes. This cross-sectional study aimed to establish normative data for the tool. Materials and Methods: Healthy volunteers aged 65 years and above were administered the Mini-Mental State Examination, Geriatric Depression Scale, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery to assess cognitive health. All subjects completed the tablet computer application without assistance. Primary outcome measure was the test performance. Regression models were built for each cognitive domain score with the covariates age, sex, and education in cognitively healthy subjects. Demographically adjusted standard scores (z-scores) were computed for each subtest. Results: A total of 283 participants (155 women, 128 men) were included in the final analysis. Participants' age was 73.8±5.2 years (mean±SD) and their level of education was 13.6±2.9 years. Mini-Mental State Examination score was 29.2±0.9 points, Geriatric Depression Scale score was 0.4±0.7 points, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery total score was 98.7±5.7 points. Older age was associated with poorer performance in the visual recognition task and in Trail Making Test B (P

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Glasgow Coma Scale Score Fluctuations are Inversely Associated With a NIRS-based Index of Cerebral Autoregulation in Acutely Comatose Patients

Background: The Glasgow Coma Scale (GCS) is an essential coma scale in critical care for determining the neurological status of patients and for estimating their long-term prognosis. Similarly, cerebral autoregulation (CA) monitoring has shown to be an accurate technique for predicting clinical outcomes. However, little is known about the relationship between CA measurements and GCS scores among neurological critically ill patients. This study aimed to explore the association between noninvasive CA multimodal monitoring measurements and GCS scores. Methods: Acutely comatose patients with a variety of neurological injuries admitted to a neurocritical care unit were monitored using near-infrared spectroscopy–based multimodal monitoring for up to 72 hours. Regional cerebral oxygen saturation (rScO2), cerebral oximetry index (COx), GCS, and GCS motor data were measured hourly. COx was calculated as a Pearson correlation coefficient between low-frequency changes in rScO2 and mean arterial pressure. Mixed random effects models with random intercept was used to determine the relationship between hourly near-infrared spectroscopy–based measurements and GCS or GCS motor scores. Results: A total of 871 observations (h) were analyzed from 57 patients with a variety of neurological conditions. Mean age was 58.7±14.2 years and the male to female ratio was 1:1.3. After adjusting for hemoglobin and partial pressure of carbon dioxide in arterial blood, COx was inversely associated with GCS (β=−1.12, 95% confidence interval [CI], −1.94 to −0.31, P=0.007) and GCS motor score (β=−1.06, 95% CI, −2.10 to −0.04, P=0.04). In contrast rScO2 was not associated with GCS (β=−0.002, 95% CI, −0.01 to 0.01, P=0.76) or GCS motor score (β=−0.001, 95% CI, −0.01 to 0.01, P=0.84). Conclusions: This study showed that fluctuations in GCS scores are inversely associated with fluctuations in COx; as COx increases (impaired autoregulation), more severe neurological impairment is observed. However, the difference in COx between high and low GCS is small and warrants further studies investigating this association. CA multimodal monitoring with COx may have the potential to be used as a surrogate of neurological status when the neurological examination is not reliable (ie, sedation and paralytic drug administration). C.W.H. receives research funding from Medtronic/Covidien, Dublin, IR. C.W.H. is the PI on an NIH-sponsored clinical study (R01 HL 92259) and he serves as a consultant to Medtronic/Covidien and Ornim Medical Inc., Foxborough, MA. L.R.-L. is the PI on an American Academy of Neurology/American Brain Foundation, Covidien/Metronic, and Ornim grant. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Ryan J. Healy, BSc, Departments of Neurology, Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD 21287 (e-mail: ryanhealy@comcast.net). Received November 21, 2017 Accepted April 19, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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High baseline neutrophil-to-lymphocyte ratio predicts worse outcome in patients with metastatic BRAF-positive melanoma treated with BRAF and MEK inhibitors

Neutrophil-to-lymphocyte ratio (NLR) has been shown to be prognostic in several solid malignancies. There are limited data regarding its value during novel therapies in patients with melanoma. The aim of the study was to assess the practical utility of this ratio in patients with BRAF-mutant melanoma treated with a combination of BRAF and MEK inhibitors (BRAFi/MEKi). We included 215 patients with inoperable or metastatic melanoma who underwent BRAFi/MEKi treatment between October 2015 and June 2017. Baseline NLR and other complete blood count-derived inflammatory markers were tested for association with overall survival and progression-free survival in univariate and multivariate models. On-treatment NLR was also assessed for relationship with these outcomes using the time-dependent Cox's proportional hazard model. Prognostic model based on NLR and lactate dehydrogenase (LDH) levels was also developed. Patients with NLR values more than four had poorer progression-free survival (P

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LncRNA MALAT-1 competitively regulates miR-124 to promote EMT and development of non-small-cell lung cancer

This study was carried out to explore the mechanism of LncRNA MALAT-1 as a competing endogenous RNA to regulate miR-124 in epithelial–mesenchymal transition and development of non-small-cell lung cancer (NSCLC). NSCLC and adjacent tissues were collected for RT-qPCR. The correlation of MALAT-1 and miR-124 was analyzed by Pearson. MALAT-1 expression was measured in NSCLC A549, NCI-H460, NCI-H529, SK-MES-1 cells, and 16HBE cells. A549 cells were selected for cell transfection experiments after the creation of six groups. Luciferase reporter assay and RNA immunoprecipitation were used to verify the relationship between MALAT-1 and miR-124. Expressions of E-cadherin and vimentin were determined by western blot. Cell variability, apoptosis, invasion, and migration were measured by MTT, FCM, transwell assay, and scratch test. LncRNA MALAT-1 expression was higher in NSCLC tissues than that in adjacent tissues, but a lower expression of miR-124 was detected in the former tissues than in the latter tissues. Compared with 16HBE cells, MALAT-1 was highly expressed in NSCLC tissues. Compared with the blank group, E-cadherin and cell apoptosis were increased, but vimentin, cell variability, cell invasion, and migration ability in the si-MALAT-1 and miR-124 mimics groups were reduced. Compared with the blank group, decreased E-cadherin and cell apoptosis and increased vimentin, cell variability, cell invasion, and migration ability were detected in the oe-MALAT-1 group. The oe-MALAT-1+miR-124 mimics group had increased E-cadherin and cell apoptosis, but decreased vimentin, cell variability, cell invasion, and migration ability in comparison with the oe-MALAT-1 group. By competitively regulating miR-124, MALAT-1 can promote epithelial–mesenchymal transition, thus accelerating the development of NSCLC. Correspondence to Lin Cai, MM, The School of Public Health, Fujian Medical University, Jiaotong Road, No. 88, Fuzhou 350001, People's Republic of China Tel/fax: +86 591 2286 2539; e-mail: cailin01010@163.com Received October 10, 2017 Accepted March 2, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of pyruvate kinase M2-regulating aerobic glycolysis on chemotherapy resistance of estrogen receptor-positive breast cancer

This study aims to explore the effect and mechanism of pyruvate kinase M2 (PKM2) on chemotherapy resistance of estrogen receptor-positive breast cancer (ER+ BC) by regulating aerobic glycolysis. The expression of PKM2 in ER+ BC MCF-7 cells, T47D cells and MCF-7/ADR cells (which are subject to adriamycin/ADR induction) were determined by quantitative real-time PCR and western blot. MCF-7/ADR (M/A) cells were grouped into blank group (M/A), negative group (M/A+NC), low expression of PKM2 group (M/A+si-PKM2 group), overexpression of PKM2 group (M/A+PKM2 group) and glycolysis inhibition group (M/A+PKM2+2-DG group). Quantitative real-time PCR and western blot were applied to measure the expressions of PKM2, multidrug resistance, and glutathione-S-transferase π. Glucose and lactic acid kit was used to detect the amount of glucose uptake and lactic production. Cell variability, clone formation ability, and cell apoptosis were respectively measured by MTT, clone formation assay, and flow cytometry. Transwell assay and scratch assay were applied for cell invasion and migration ability. By overexpressing PKM2 in MCF-7 and T47D cells and using 2-DG, the effect on sensitivity of adriamycin amycin was explored. MCF-7/ADR cells have both elevated mRNA and protein expressions of PKM2 when compared with MCF-7 cells (both P

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Renal Ewing sarcoma treated with apatinib

Renal Ewing sarcoma (RES) is an extremely rare disease. The standard treatment for this disease is lacking, and clinical experience needs to be accumulated. Here, we report a case of RES that rapidly developed to metastatic disease and was refractory to radiotherapy and chemotherapy; however, the case obtained a partial response based on Choi criteria by orally taking antiangiogenic drug apatinib. Our case suggests that apatinib may be a therapeutic option for RES. Correspondence to Ji-Yan Liu, MD, PhD, The State Key Laboratory of Biotherapy, Department of Medical Oncology, West China Medical School, Cancer Center, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu 610041, Sichuan Province, China Tel: +86 288 542 3262; fax: +86 288 542 3609; e-mail: liujiyan1972@163.com Received December 7, 2017 Accepted March 15, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Role of LKB1 in migration and invasion of Cr(VI)-transformed human bronchial epithelial Beas-2B cells

Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells. The mechanism underlying its carcinogenicity is unclear in terms of how it facilitates metastases. Cr(VI) compounds are reported to briefly promote cell migration in a concentration-dependent manner and oncogene liver kinase B1 (LKB1) was reduced in Cr(VI)-transformed cells. Overexpression of LKB1 in Beas-2B-Cr [Cr(VI) malignantly transformed Beas-2B cells] suppressed cell migration and invasion and inactivated FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, which contribute to cell migration and invasion. Silencing LKB1 with siRNA promoted migration and invasion, and activated these downstream proteins. Long-term exposure to Cr(VI) enhanced the migration and invasiveness of Beas-2B cells and reduced the expression of LKB1, while activating these proteins as mentioned above. Data suggest that LKB1 may regulate downstream proteins such as FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, and affect the migration and invasiveness of Beas-2B-Cr cells. * Jian Lu and Zhongping Zhou contributed equally to the writing of this article. Correspondence to Jian Lu, PhD, Jiangsu University, No.301, Xuefu Road, Jingkou District, Zhenjiang, Jiangsu 212013, China Tel: +86 511 8878 8776; fax: +86 511 8879 1923; e-mail: lujian@ujs.edu.cn Correspondence to Zhanao Wu, MS, No. 359 Hospital, No.8, Zhongshan East Road, Zhenjiang, Jiangsu 212050, China Tel/fax: +86 511 8333 5901; e-mail: wza_007@qq.com Received November 10, 2017 Accepted April 9, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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An update on the management of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) are a rare and heterogeneous group of neoplasia and differ in their clinical presentation, behavior, and prognosis based on both histological features and cancer stage at the time of diagnosis. Although small-sized tumors can be surgically resected, locally advanced and metastatic tumors confer a poor prognosis. In addition, only limited treatment options are available to the latter group of patients with PNETs, such as hormonal analogs, cytotoxic agents, and targeted therapy. In selected patients, liver-directed therapies are also used. As expected, clinicians taking care of these patients are challenged to develop an effective and comprehensive treatment strategy for their patients amid a wide variety of treatment modalities. Targeted therapy for PNETs is limited to sunitinib and everolimus. Presently, a number of clinical studies are ongoing to assess the efficacy of newer targeted agents alone and in combination with previous agents for the treatment of advanced PNETs. The authors reviewed the current treatment and also discussed the emerging agents and emphasized the need to identify biomarkers. Correspondence to Muhammad W. Saif, MBBS, MD, Department of Medicine and Cancer Center, Tufts Medical Center, 800 Washington Street Box 245, Boston, MA 02111, USA Tel: +1 617 636 5627; fax: +1 617 636 8535; e-mail: wsaif@tuftsmedicalcenter.org Received January 23, 2018 Accepted March 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Perioperative Management in Robotic Surgery, 1st ed

No abstract available

https://ift.tt/2ItKGdX

Frozen in Time: A History of the Synthesis of Nitrous Oxide and How the Process Remained Unchanged for Over 2 Centuries

Three major factors have contributed to the unrivaled popularity of nitrous oxide (N2O) among anesthetists in the 20th century and beyond: its impressive safety profile, its affordability, and its rapid induction and emergence times. These 3 characteristics of N2O have been discussed and written about extensively throughout the medical literature. Nonetheless, the characteristic that contributed most to N2O's initial discovery—the elegance and simplicity of its synthesis—has received substantially less attention. Although N2O was first used as an anesthetic in Hartford, CT, in 1844, it had been identified and synthesized as a distinct gas in the late 18th century. In this article, we track the developments in the recognition and early synthesis of N2O, highlight the major players credited with its discovery, and examine its evolution from the late 1700s to today. The discovery and assimilation of N2O into common medical practice, alongside ether and chloroform, heralded a new paradigm in surgical medicine—one that no longer viewed pain as a fundamental component of surgical medicine. Its continued usage in modern medicine speaks to the brilliance and skill of the chemists and scientists involved in its initial discovery. Accepted for publication March 30, 2018. Funding: Intramural. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Manisha S. Desai, MD, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655. Address e-mail to manisha.desai@umassmemorial.org. © 2018 International Anesthesia Research Society

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In Response

No abstract available

https://ift.tt/2GxtPRG

Is Neuraxial Anesthesia Appropriate for Cesarean Delivery in All Cases of Morbidly Adherent Placenta?

No abstract available

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Understanding Conflict Management Styles in Anesthesiology Residents

BACKGROUND: Successful conflict resolution is vital for effective teamwork and is critical for safe patient care in the operating room. Being able to appreciate the differences in training backgrounds, individual knowledge and opinions, and task interdependency necessitates skilled conflict management styles when addressing various clinical and professional scenarios. The goal of this study was to assess conflict styles in anesthesiology residents via self- and counterpart assessment during participation in simulated conflict scenarios. METHODS: Twenty-two first-year anesthesiology residents (first postgraduate year) participated in this study, which aimed to assess and summarize conflict management styles by 3 separate metrics. One metric was self-assessment with the Thomas-Kilmann Conflict Mode Instrument (TKI), summarized as percentile scores (0%–99%) for 5 conflict styles: collaborating, competing, accommodating, avoiding, and compromising. Participants also completed self- and counterpart ratings after interactions in a simulated conflict scenario using the Dutch Test for Conflict Handling (DUTCH), with scores ranging from 5 to 25 points for each of 5 conflict styles: yielding, compromising, forcing, problem solving, and avoiding. Higher TKI and DUTCH scores would indicate a higher preference for a given conflict style. Sign tests were used to compare self- and counterpart ratings on the DUTCH scores, and Spearman correlations were used to assess associations between TKI and DUTCH scores. RESULTS: On the TKI, the anesthesiology residents had the highest median percentile scores (with first quartile [Q1] and third quartile [Q3]) in compromising (67th, Q1–Q3 = 27–87) and accommodating (69th, Q1–Q3 = 30–94) styles, and the lowest scores for competing (32nd, Q1–Q3 = 10–57). After each conflict scenario, residents and their counterparts on the DUTCH reported higher median scores for compromising (self: 16, Q1–Q3 = 14–16; counterpart: 16, Q1–Q3 = 15–16) and problem solving (self: 17, Q1–Q3 = 16–18; counterpart: 16, Q1–Q3 = 16–17), and lower scores for forcing (self: 13, Q1–Q3 = 10–15; counterpart: 13, Q1–Q3 = 13–15) and avoiding (self: 14, Q1–Q3 = 10–16; counterpart: 14.5, Q1–Q3 = 11–16). There were no significant differences (P > .05) between self- and counterpart ratings on the DUTCH. Overall, the correlations between TKI and DUTCH scores were not statistically significant (P > .05). CONCLUSIONS: Findings from our study demonstrate that our cohort of first postgraduate year anesthesiology residents predominantly take a more cooperative and problem-solving approach to handling conflict. By understanding one's dominant conflict management style through this type of analysis and appreciating the value of other styles, one may become better equipped to manage different conflicts as needed depending on the situations. Accepted for publication April 4, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Brenda G. Fahy, MD, MCCM, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Rd, PO Box 100254, Gainesville, FL 32610. Address e-mail to bfahy@anest.ufl.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2wVuZqS

Hagberg and Benumof’s Airway Management, 4th ed

No abstract available

https://ift.tt/2IzL9f2

Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

https://ift.tt/2wVuQDQ

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public–private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses. Accepted for publication March 5, 2018. Funding: None. 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 (https://ift.tt/KegmMq). The views expressed in this article are those of the authors, none of whom has financial conflicts of interest specifically related to the issues discussed. At the time of the meeting (November 17–19, 2016) on which this article is based, several authors were employed by a pharmaceutical company or had received consulting fees or honoraria from 1 or more pharmaceutical or device companies. The authors of this article who were not employed by industry at the time of the meeting received (or their universities received) travel stipends, hotel accommodations, and meals during the meeting from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership. No official endorsement by the US Food and Drug Administration or the pharmaceutical and device companies that have provided unrestricted grants to support the activities of ACTTION should be inferred. Financial support for this project was provided by ACTTION, which has received research contracts, grants, or other revenue from the US Food and Drug Administration, multiple pharmaceutical and device companies, philanthropy, and other sources. Reprints will not be available from the authors. Address correspondence to Denham S. Ward, MD, PhD, Department of Anesthesiology and Perioperative Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 604, Rochester, NY 14642. Address e-mail to Denham_Ward@URMC.Rochester.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2wTKVK5

The Impact of Anesthesia-Influenced Process Measure Compliance on Length of Stay: Results From an Enhanced Recovery After Surgery for Colorectal Surgery Cohort

BACKGROUND: Process measure compliance has been associated with improved outcomes in enhanced recovery after surgery (ERAS) programs. Herein, we sought to assess the impact of compliance with measures directly influenced by anesthesiology in an ERAS for colorectal surgery cohort. METHODS: From January 2013 to April 2015, data from 1140 consecutive patients were collected for all patients before (pre-ERAS) and after (ERAS) implementation of an ERAS program. Compliance with 9 specific process measures directly influenced by the anesthesiologist or acute pain service was analyzed to determine the impact on hospital length of stay (LOS). RESULTS: Process measure compliance was associated with a stepwise reduction in LOS. Patients who received >4 process measures (high compliance) had a significantly shorter LOS (incident rate ratio [IRR], 0.77; 95% CI, 0.70–0.85); P

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Population Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children Undergoing Ambulatory Surgery

BACKGROUND: Dexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK–PD) in Mexican children 2–18 years of age who were undergoing outpatient surgical procedures. METHODS: Thirty children 2–18 years of age with American Society of Anesthesiologists physical status score of I/II were enrolled in this study. DEX (0.7 µg/kg) was administered as a single-dose intravenous infusion. Venous blood samples were collected, and plasma DEX concentrations were analyzed with a combination of high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry. Population PK–PD models were constructed using the Monolix program. RESULTS: A 2-compartment model adequately described the concentration–time relationship. The parameters were standardized for a body weight of 70 kg by using an allometric model. Population parameters estimates were as follows: mean (between-subject variability): clearance (Cl) (L/h × 70 kg) = 20.8 (27%); central volume of distribution (V1) (L × 70 kg) = 21.9 (20%); peripheral volume of distribution (V2) (L × 70 kg) = 81.2 (21%); and intercompartmental clearance (Q) (L/h × 70 kg) = 75.8 (25%). The PK–PD model predicted a maximum mean arterial blood pressure reduction of 45% with an IC50 of 0.501 ng/ml, and a maximum heart rate reduction of 28.9% with an IC50 of 0.552 ng/ml. CONCLUSIONS: Our results suggest that in Mexican children 2–18 years of age with American Society of Anesthesiologists score of I/II, the DEX dose should be adjusted in accordance with lower DEX clearance. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication March 27, 2018. Funding: None. 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 (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Gustavo Lugo-Goytia, PhD, Departamento de Anestesiología y Medicina Crítica, Instituto Nacional de Ciencias Médicas y Nutrición, México; and Respiratory Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias, México. Address e-mail to lugogoy@yahoo.com.mx. © 2018 International Anesthesia Research Society

https://ift.tt/2wXObnG

Benefit and Harm of Adding Epinephrine to a Local Anesthetic for Neuraxial and Locoregional Anesthesia: A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses

BACKGROUND: This systematic review examines the benefit and harm of adding epinephrine to local anesthetics for epidural, intrathecal, or locoregional anesthesia. METHODS: We searched electronic databases to October 2017 for randomized trials comparing any local anesthetic regimen combined with epinephrine, with the same local anesthetic regimen without epinephrine, reporting on duration of analgesia, time to 2 segments regression, or any adverse effects. Trial quality was assessed using the Cochrane risk of bias tool and a random-effects model was used. Trial sequential analyses (TSA) were applied to identify the information size (IS; number of patients needed to reach a definite conclusion) and were set to detect an increase or decrease of effect of 30%–50%, depending on the end point considered. Alpha levels were adjusted (1%) for multiple outcome testing. RESULTS: We identified 70 trials (3644 patients, 17 countries, from 1970 to 2017). Median number of patients per trial was 44 (range, 9–174). Thirty-seven trials (1781 patients) tested epinephrine for epidural, 27 (1660) for intrathecal, and 6 (203) for locoregional anesthesia (sciatic, femoral, popliteal, axillary blocks). TSA enabled us to conclude that adding epinephrine to epidural local anesthetics could not decrease postoperative pain intensity by 30%, and did not impact the risk of intraoperative arterial hypotension. IS was insufficient to conclude on the impact of epinephrine on the risk of motor block (IS, 4%), arterial hypotension (20%), urinary retention (23%), or pain intensity at rest (27%) during labor. TSA confirmed that adding epinephrine to intrathecal local anesthetics increased the duration of motor block (weighted mean difference [WMD] 64 minutes; 99% CI, 37–91), analgesia (WMD 34 minutes; 99% CI, 6–62), and the time to 2 segments regression (WMD 20 minutes; 99% CI, 11–28). IS was insufficient to conclude on its impact on arterial hypotension (IS, 15%), or when administrated in a combined spinal-epidural, on motor block (IS, 11%) or arterial hypotension (IS, 11%). Adding epinephrine to local anesthetics for a locoregional block increased the duration of analgesia (WMD 66 minutes; 98% CI, 32–100]). CONCLUSIONS: Adding epinephrine to intrathecal or locoregional local anesthetics prolongs analgesia and motor block by no more than 60 minutes. The impact of adding epinephrine to epidural local anesthetics or to a combined spinal-epidural remains uncertain. Accepted for publication March 27, 2018. Funding: None. 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 (https://ift.tt/KegmMq). Protocol registration: International prospective register of systematic reviews (PROSPERO) (CRD: 42015026148). Reprints will not be available from the authors. Address correspondence to Clément Tschopp, MD, MSc, Division of Anesthesiology, University Hospital of Zürich, Rämistrasse 100, Zürich CH-8091, Switzerland. Address e-mail to clement.tschopp@usz.ch. © 2018 International Anesthesia Research Society

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The impact of contour variation on tumour control probability in anal cancer

While intensity modulated radiotherapy (IMRT) has been widely adopted for the treatment of anal cancer (AC), the added contour complexity poses potential risks. This study investigates the impact of contour va...

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Breast-conservation Therapy After Neoadjuvant Chemotherapy Does Not Compromise 10-Year Breast Cancer–specific Mortality

Objectives: Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery by downstaging disease in patients with breast cancer. The aim of this study was to determine whether patients who received neoadjuvant chemotherapy have equal survival after breast-conservation therapy compared with mastectomy. Material and Methods: Using the New Jersey State Cancer Registry (NJSCR) patients with a primary breast cancer diagnosed between 1998 and 2003 who underwent neoadjuvant chemotherapy were selected (n=1,468). Of those, only patients who received lumpectomy plus radiation (n=276) or mastectomy without radiation (n=442) were included in the analysis. The main outcome measured included 10-year breast cancer–specific mortality, with 90% of patients with known vital status through the end of 2011. Results: Baseline characteristics did not differ significantly between the breast-conservation and mastectomy without radiation groups except with respect to summary stage and lymph node involvement. After propensity score matching these differences were no longer statistically significant; however, both estrogen and progesterone status achieved statistical significance. The Kaplan-Meier survival curve showed that the breast-conservation group had significantly higher breast cancer–specific survival than the mastectomy group (P=0.0046). After adjusting for the propensity score in the regression model, the breast-conservation group continued to show significantly better survival than the mastectomy group (hazard ratios, 0.46; 95% confidence interval, 0.27-0.78). Conclusions: This study is consistent with previous research showing that breast-conserving surgery after neoadjuvant chemotherapy does not reduce breast cancer–specific survival. In fact, patients undergoing breast-conservation after neoadjuvant therapy appeared to have better survival than patients undergoing mastectomy without radiation. Cancer data used in this study were provided by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey Department of Health, which is funded by the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute under contract HHSN261201300021I, the National Program of Cancer Registries (NPCR), Centers for Disease Control and Prevention under grant 5U58DP003931-02 as well as the State of New Jersey and the Rutgers Cancer Institute of New Jersey. The authors declare no conflicts of interest. Reprints: Renee L. Arlow, MD, Department of Surgery, Rutgers Robert Wood Johnson Medical School, 51 French Street, MEB 596, P.O. Box 19, New Brunswick, NJ 08901. E-mails: renee.arlow@gmail.com; renee.arlow@uphs.upenn.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity

Objectives: Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Materials and Methods: Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Results: Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Conclusions: Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure. M.C. and N.S. contributed equally. Portions of this work were presented as an oral presentation at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting in Boston, MA. The authors declare no conflicts of interest. Reprints: Mudit Chowdhary, MD, Rush University Medical Center, Department of Radiation Oncology, 500 South Paulina, Chicago, IL 60612. E-mail: mchowdharymd@gmail.com. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 12 Matched-pair Analysis

Background: Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. Materials and Methods: From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER−/PR−/HER2− and either CK 5/6+ or EGFR+) was performed for BRCA+ patients who developed BM and their matched controls. Results: We analyzed 60 patients: 20 BRCA+ and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA+ patients and 97% for BRCA− controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA+ patients. All 3 BRCA1+ patients who developed BM were of a basal-type triple negative phenotype. Conclusions: Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors. The authors declare no conflicts of interest. Reprints: Peter J. Zavitsanos, MD, Department of Radiation Oncology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903. E-mail: peter.zavitsanos@lifespan.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Phase II Study of Celecoxib With Irinotecan, 5-Fluorouracil, and Leucovorin in Patients With Previously Untreated Advanced or Metastatic Colorectal Cancer

Objective: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Cyclooxygenase-2 (COX-2) overexpression is associated with increased tumor invasiveness and proliferation in CRC, and COX-2 inhibition has demonstrated chemopreventive activity. This study investigated the addition of celecoxib, a selective COX-2 inhibitor, to the irinotecan, 5-fluorouracil, and leucovorin (IFL) regimen for patients with previously untreated metastatic CRC. Patients and Methods: Forty-seven patients enrolled in this single-arm phase II study received celecoxib at 400 mg orally twice daily in combination with weekly irinotecan (125 mg/m2), 5-fluorouracil (500 mg/m2), and leucovorin (20 mg/m2) for 4 weeks every 6 weeks. The primary endpoint was response rate (RR) as measured by Response Evaluation Criteria in Solid Tumors. The protocol was amended midway to additionally exclude patients with Eastern Cooperative Oncology Group performance status 2 and require all patients with specific cardiovascular risk factors to take daily aspirin (81 mg). Results: The objective RR was 31.9% (95% confidence interval [CI], 19%-47%). Median progression-free survival was 8.7 months (95% CI, 5.8-10.6), and the median overall survival was 19.7 months (95% CI, 15.4-22.8). All cardiac events were observed before protocol modification. The median overall survival before and after protocol modification was 11.4 versus 24.2 months, respectively (P

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The Significance of Para-Aortic Nodal Size and the Role of Adjuvant Systemic Chemotherapy in Cervical Cancer: An Institutional Experience

Objective: Cervical cancer metastatic to the para-aortic lymph nodes (PALNs) carries a poor prognosis. Despite extended-field radiation therapy (EFRT), only 30% to 50% of patients will survive 3 years. We sought to examine the treatment regimens used, associated toxicities, and treatment outcomes in patients with cervical cancer metastatic to PALN. Methods: A retrospective review was performed of all patients with cervical cancer treated at a single institution between January 1, 2007 and November 1, 2014. Included patients had PALN metastases as the most distant site of disease, and all treatment plans were designated as curative. Excluded patients had other distant disease or treatment plans considered palliative. Standard treatment consisted of EFRT with concurrent platinum-based chemotherapy. Results: Fifty-one of 344 patients (14.8%) fulfilled the inclusion criteria. The median age was 48.4 years. Forty-four patients received standard EFRT; 7 also received adjuvant platinum/taxane chemotherapy. Thirty-nine of 51 (76%) of patients achieved a complete response to primary treatment. Twelve of 51 (24%) had persistent disease or progression at the completion of treatment. Of responders, 15 of 39 (38%) recurred for an overall treatment failure rate of 27 of 51 (53%). Nineteen of 27 (70%) of treatment failures occurred outside the radiated field. Adjuvant chemotherapy following EFRT was not predictive of progression-free survival or overall survival. PALN diameter ≥1 cm was a significant negative prognostic indicator for overall survival. Conclusions: Over half of patients with cervical cancer metastatic to the PALN failed extended-field chemoradiation. Most failures occurred outside the radiated field suggesting PALN involvement is a surrogate marker of systemic disease. These findings underscore the need for effective systemic therapy, especially in patients with PALN ≥1 cm in size. The authors declare no conflicts of interest. Reprints: Travis T. Sims, MD, 5323 Harry Hines Blvd., Dallas, TX 75390-9032. E-mail: travis.sims@phhs.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Regional Lymph Node Metastases in Groin Sarcomas: A Diagnostic and Therapeutic Challenge

Introduction: The evaluation of lymph nodes and the role of groin dissection for groin sarcomas has been controversial where there have not been previous studies or guidelines published. In this study, we aim to first formulate a clinical approach in the evaluation of regional lymph nodal metastases. Second, we aim to also evaluate the role of regional lymphadenectomy in the setting of pathologically involved regional lymph nodes for groin sarcomas. Materials and Methods: In total, 43 consecutive patients with groin sarcomas underwent treatment at the National Cancer Centre Singapore between 2002 and 2015. Univariate comparisons were performed using the log-rank test. A Cox multivariate analysis was performed for disease-specific survival to identify independent prognostic factors. Results: The median disease-free survival was 18 months (range, 1 to 180 mo). The median overall survival (OS) was 28 months (range, 3 to 180 mo). In total, 28 patients underwent a groin dissection. Of the 28 patients who underwent groin dissections, 15 had negative lymph node involvement, 7 had positive lymph node involvement and 6 had lymphovascular invasion. On univariate analysis, grade (P=0.047) and clinical and/or radiological involvement (P=0.039) were significant for regional lymph nodal metastases. The 5-year OS for patients with positive lymph nodes was 31%. Conclusions: Our study suggests that the evaluation of lymph nodes via groin dissections in groin sarcomas in the Asian population should be based primarily on clinical and radiologic evidence. Regional lymph node dissection seems to confer OS benefit in patients with these high-risk tumors and can improve local control of disease. The authors declare no conflicts of interest. Reprints: Melissa Ching Ching Teo, MBBS, FRCS, Division of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore. E-mail: melissa.teo.c.c@singhealth.com.sg. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Utility of Diagnostic Laparoscopy in Patients Being Evaluated for Cytoreductive Surgery and Hyperthermic Peritoneal Chemotherapy

Background: To assess the role of diagnostic laparoscopy (DL) to evaluate candidates for optimal cytoreduction surgery of peritoneal carcinomatosis (PC) combined with hyperthermic intraperitoneal chemotherapy in a consecutive series. Methods: The characteristics of 31 patients undergoing DL between August 2012 and October 2016 for a diagnosis of PC secondary to digestive neoplasms were retrospectively reviewed. Results: Laparoscopic evaluation was successful and well-tolerated in 100% patients (N=31). In 17 patients (54.8%) the PC was deemed unresectable. A cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy was performed in 10 of 12 patients with PC considered resectable at laparoscopy wity a positive predictive value of 83.3%. One patient was diagnosed with more extensive disease than that as assessed by the DL at the time of laparotomy and 1 patient elected not to have further surgery. There were no port-site recurrences and morbidity at mean follow-up of 19.3 months. Conclusions: Laparoscopic assessment of PC is a useful tool to assess the complete resectability of peritoneal surface disease in patients for whom there is inadequate information concerning disease extent. DL also helps selected patients to avoid an unnecessary laparotomy. The authors declare no conflicts of interest. Reprints: Alessio Pigazzi, MD, PhD, 333 City Blvd West, Suite 850, Orange, CA 92868. E-mail: apigazzi@uci.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Utilization of an Alternative Docetaxel-based Intraperitoneal Chemotherapy Regimen in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma: A Continued Need for Ovarian Cancer Patients

Objective: The objective of this study was to report the tolerability and toxicity of a regimen consisting of intravenous (IV) docetaxel and intraperitoneal (IP) cisplatin and paclitaxel with granulocyte colony-stimulating factor support. Materials and Methods: We conducted a retrospective cohort study of patients with surgical stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma treated with an outpatient IP chemotherapy regimen consisting of docetaxel 75 mg/m2 IV and cisplatin 75 mg/m2 IP day 1 followed by paclitaxel 60 mg/m2 IP day 8 every 21 days. Grade 3 and 4 toxicity, dose delays and reductions, port complications, and tolerability are reported. Outcomes, including response rate, progression-free survival (PFS), overall survival (OS) are also reported. Results: A total of 60 patients received this IP regimen. Most common toxicities included neutropenia (47%), gastrointestinal (28%), and anemia (25%). Most patients (85%) experienced no IP port complications. Dose delay or reduction was required in 30% of patients. Two-thirds completed all prescribed cycles, with 80% of total planned cycles completed. Complete response was achieved for 88%, and 43% are currently without evidence of disease. Median PFS for all patients was 25.5 months (95% confidence interval [CI], 20.4-30.5 mo) while OS for all patients was 56.8 months (95% CI, 47.7-65.9 mo). For the 44 patients with stage III disease, median PFS was 22.1 months (95% CI, 16.3-28.0 mo), while median OS was 56.8 months (95% CI, 47.3-66.3 mo). Conclusions: This docetaxel-based IP chemotherapy regimen demonstrates an improved tolerability profile compared with GOG172. Additional evaluations on alternative IP regimens remain warranted. Short follow-up time limits survival assessment, but results are encouraging. Presented as a poster presentation at the Society of Gynecologic Oncology Annual Meeting on Women's Cancer, 2015, Chicago, IL. Supported in part by NIH 3P30CA013148-43S3 and 5K12HD0012580-15 to C.A.L. and K.S.B. The authors declare no conflicts of interest. Reprints: Charles A. Leath III, MD, MSPH, Division of Gynecologic Oncology, University of Alabama at Birmingham, 1700 6th Avenue South, Room 10250, Birmingham, AL 35233. E-mail: cleath@uabmc.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Single-agent Bevacizumab in Recurrent Glioblastoma After Second-line Chemotherapy With Fotemustine: The Experience of the Italian Association of Neuro-Oncology

Objectives: Bevacizumab is an anti-vascular endothelial growth factor antibody used in the treatment of recurrent glioblastoma (GBM). Despite the large number of studies carried out in patients with recurrent GBM, little is known about the administration of this angiogenesis inhibitor after the failure of the second-line chemotherapy. Materials and Methods: In this retrospective multicenter study, on behalf of the Italian Association of Neuro-Oncology, we reported the results obtained in 51 patients with recurrent GBM treated with single-agent bevacizumab after the failure of second-line chemotherapy with fotemustine. Results: In March 2016, at the time of data analysis, 3 patients (14.4%) were still alive with stable disease, whereas 48 died due to disease progression. Kaplan-Meier estimated median survival from the diagnosis of GBM was 28 months (95% confidence interval [CI], 22.1-33.9 mo). Median survival measured from the beginning of fotemustine and bevacizumab therapy were 11.3 (95% CI, 8.4-13.6 mo) and 6 months (95% CI, 3.8-8.1 mo), respectively. The 6- and 12-month progression free survival rates from the beginning of bevacizumab treatment were 18% and 13%, respectively. Conclusions: On the basis of our data, in patients with recurrent GBM, the failure of a second-line chemotherapy with cytotoxic agents might not exclude the administration of bevacizumab as third-line chemotherapy. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent for treatments was obtained from all individual participants included in the study. The authors declare no conflicts of interest. Reprints: Francesco Pasqualetti, MD, PhD, Department of Oncology, Division of Radiation Oncology, Azienda Ospedaliero Universitaria Pisana, Via Roma 67, Pisa 56123, Italy. E-mails: francep24@hotmail.com, f.pasqualetti@ao-pisa.toscana.it. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Absolute dose verification of static intensity modulated radiation therapy (IMRT) with ion chambers of various volumes and TLD detectors

Publication date: July–August 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 4
Author(s): Hediye Acun-Bucht, Ebru Tuncay, Emin Darendeliler, Gönül Kemikler
AimThis study aims at examining absolute dose verification of step-and-shoot intensity modulated radiation treatment (IMRT) of prostate and brain patients by use of ion chambers of two different volumes and thermoluminescent detectors (TLD).BackgroundThe volume of the ion chamber (IC) is very important for absolute dose verification of IMRT plans since the IC has a volume average effect. With TLD detectors absolute dose verification can be done measuring the dose of multiple points simultaneously.Materials and methodsIon chambers FC65-P of volume 0.65cc and semiflex of volume 0.125cc as well as TLDs were used to measure the central axis absolute dose of IMRT quality assurance (QA) plans. The results were compared with doses calculated by a treatment planning system (TPS). The absolute doses of off axis points located 2cm and 4cm away from the isocenter were measured with TLDs.ResultsThe measurements of the 0.125cc ion chamber were found to be closer to TPS calculations compared to the 0.65cc ion chamber, for both patient groups. For both groups the root mean square (RMS) differences between doses of the TPS and the TLD detectors are within 3.0% for the central axis and points 2cm away from the isocenter of each axis. Larger deviations were found at the field edges, which have steep dose gradient.ConclusionsThe 0.125cc ion chamber measures the absolute dose of the isocenter more accurately compared to the 0.65cc chamber. TLDs have good accuracy (within 3.0%) for absolute dose measurements of in-field points.



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The current status of immunotherapy for cervical cancer

Publication date: Available online 18 May 2018
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Cecilia Orbegoso, Krithika Murali, Susana Banerjee
BackgroundImmunotherapy has been proven effective in several tumours, hence diverse immune checkpoint inhibitors are currently licensed for the treatment of melanoma, kidney cancer, lung cancer and most recently, tumours with microsatellite instability. There is much enthusiasm for investigating this approach in gynaecological cancers and the possibility that immunotherapy might become part of the therapeutic landscape for gynaecological malignancies.Cervical cancer is the fourth most frequent cancer in women worldwide and represents 7.9% of all female cancers with a higher burden of the disease and mortality in low- and middle-income countries. Cervical cancer is largely a preventable disease, since the introduction of screening tests, the recognition of the human papillomavirus (HPV) as an etiological agent, and the subsequent development of primary prophylaxis against high risk HPV subtypes. Treatment for relapsed/advanced disease has improved over the last 5 years, since the introduction of antiangiogenic therapy. However, despite advances, the median overall survival for advanced cervical cancer is 16.8 months and the 5-year overall survival for all stages is 68%. There is a need to improve outcomes and immunotherapy could offer this possibility. Clinical trials aim to understand the best timing for immunotherapy, either in the adjuvant setting or recurrent disease and whether immunotherapy, alone or in combination with other agents, improves outcomes.



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8th International conference on Tumor Microenvironment, Lisbon, Portugal June 10-14, 2018

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High neutrophil to lymphocyte ratio and decreased CD69+NK cells represent a phenotype of high risk in early-stage breast cancer patients

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Downregulation of PDIA3 inhibits proliferation and invasion of human acute myeloid leukemia cells

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miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R

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Recurrent Retroperitoneal Liposarcoma: a Case Report and Literature Review

Abstract

This is a case report of a 61-year-old male patient, presented with fifth recurrence of retroperitoneal liposarcoma and operated for six times. Literature review on retroperitoneal liposarcoma biology, recurrence pattern, role of surgery in primary tumor, and recurrent tumor, adjuvant therapy, role of multivisceral resection, and palliative surgery.

https://ift.tt/2GxtXk5

Feasibility, Safety, and Surgical Outcome of Robotic Hemithyroidectomy Via Transaxillary and Retroauricular Approach: an Institutional Experience

Abstract

The aim of this observational prospective study was to determine the technical feasibility, safety, and adequacy of robotic hemithyroidectomy. From April 2015 to May 2016, 16 patients with solitary thyroid lesion underwent robotic hemithyroidectomy using the Da Vinci® Si Surgical system. Patients were observed and data were recorded on surgical time, blood loss, complications, and functional outcome of the patients. A total of 16 patients (3 males and 13 females; mean age 39.9 years) underwent robotic hemithyroidectomy after evaluation for solitary thyroid nodule with a mean nodule size of 2.2 ± 0.3 cm. Fiber-optic laryngoscopy (FOL) was normal in all cases pre-operatively. Five patients were operated by transaxillary approach, the rest by retroauricular (facelift) approach. Mean pocket dissection time was 42 min for transaxillary and 40 min for retroauricular approach. Mean operative console time was 59.4 min for transaxillary and 52.6 min for retroauricular approach. Average blood loss was 45 ml. Mean hospital stay was 1.5 days. None of the patients had any post-operative complication on follow-up. One patient had restricted left vocal cord mobility which improved in 3 months. Mean pain score was 0.25 ± 0.4 and average speech score was 0.5 ± 0.2 at 3 months. Post-operatively, all patients had adequate swallowing with no episode of aspiration. Robotic hemithyroidectomy is a safe, feasible, and oncologically safe procedure. It has benefits in terms of better scar cosmesis than open surgery.

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Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium

Abstract

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium—Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52–67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41–2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24–0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00–1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13–3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13–2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02–2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

https://ift.tt/2IXCu58

Subjective social status and mortality: the English Longitudinal Study of Ageing

Abstract

Self-perceptions of own social position are potentially a key aspect of socioeconomic inequalities in health, but their association with mortality remains poorly understood. We examined whether subjective social status (SSS), a measure of the self-perceived element of social position, was associated with mortality and its role in the associations between objective socioeconomic position (SEP) measures and mortality. We used Cox regression to model the associations between SSS, objective SEP measures and mortality in a sample of 9972 people aged ≥ 50 years from the English Longitudinal Study of Ageing over a 10-year follow-up (2002–2013). Our findings indicate that SSS was associated with all-cause, cardiovascular, cancer and other mortality. A unit decrease in the 10-point continuous SSS measure increased by 24 and 8% the mortality risk of people aged 50–64 and ≥ 65 years, respectively, after adjustment for age, sex and marital status. The respective estimates for cardiovascular mortality were 36 and 11%. Adjustment for all covariates fully explained the association between SSS and cancer mortality, and partially the remaining associations. In people aged 50–64 years, SSS mediated to a varying extent the associations between objective SEP measures and all-cause mortality. In people aged ≥ 65 years, SSS mediated to a lesser extent these associations, and to some extent was associated with mortality independent of objective SEP measures. Nevertheless, in both age groups, wealth partially explained the association between SSS and mortality. In conclusion, SSS is a strong predictor of mortality at older ages, but its role in socioeconomic inequalities in mortality appears to be complex.

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Hypertensive disorders of pregnancy and subsequent maternal cardiovascular health

Abstract

To examine associations between hypertensive pregnancy disorders and maternal cardiovascular disease (CVD) in later life. We examined the associations between blood pressure (BP) in pregnancy, gestational hypertension (GH) and preeclampsia (PE) with cardiovascular measurements 6 years after index pregnancy among 4912 women participating in the Generation R Study, the Netherlands. BP, left ventricular mass (LV mass), aortic root diameter (AOD), left atrial diameter, fractional shortening, and carotid-femoral pulse wave velocity (PWV). Early pregnancy systolic and diastolic BP were associated with more adverse maternal cardiovascular measurements and a higher incidence of chronic hypertension 6 years after pregnancy. GH was associated with a higher BP, a higher PWV, a larger AOD and an increased LV mass 6 years after index pregnancy. Compared to previous normotensive pregnancies these women had a sixfold increased risk to develop chronic hypertension after pregnancy (OR 6.6, 95% CI 4.6–9.5). Compared to women with a normotensive pregnancy, women with PE had a higher BP and a higher risk of chronic hypertension (OR 4.5, 95% CI 2.6–7.8) at follow-up. After adjustment for BMI at follow-up in all the analyses on GH, PE and cardiovascular measurements, effect estimates attenuated up to 65%, but remained significant. Both GH and PE are associated with markers of adverse maternal cardiovascular health after pregnancy with an increased risk of chronic hypertension. Women with GH and PE may be offered long-term cardiovascular follow-up incorporated in CVD risk management guidelines.

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Pure low-grade DCIS in a male patient: a case report

Abstract

Breast cancer in males represents a small proportion of all cancers diagnosed. Pure ductal carcinoma in situ (DCIS), a low-grade form of breast cancer, is even more rare in male patients. We present a case of a 47-year-old male patient with a tender breast lump that was noted for 6 months. He was subsequently found to have a low grade, pure micropapillary and cribriform type DCIS with no evidence of invasive disease. Current literature does not provide distinct guidelines regarding management of male breast cancer, and it is currently managed in a similar fashion to female breast cancer.

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Splenic myoid angioendothelioma mimicking metastatic disease in an 8-year-old with Stage IV Wilms tumour

Myoid angioendothelioma are rare and benign vascular tumours of the spleen. Radiographic evaluation and diagnosis is often challenging and subjecting tissue samples to immuhistochemical analysis is often required to make a definitive diagnosis. Myoidangioendotheliomas can be managed with open or laparoscopic splenectomy with minimal risk of recurrent disease. Herein, we present a case of a myoid angioendothelioma in a patient with stage IV Wilms' tumour.

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Coexisting squamous cell carcinoma and high-grade neuroendocrine carcinoma, small cell type: a rare collision in cervix

Collision tumours of the uterine cervix are extremely uncommon with exact incidence not known. Unlike squamous cell carcinoma (SCC) and adenocarcinoma that are known to coexist, small cell neuroendocrine carcinoma (SCNEC) is rarely documented with other histological types in the cervix. We report such rare case of a collision tumour in cervix displaying dual histological component of SCNEC and SCC in a 36-year-old woman. The case is being presented because of its rarity and represents a unique and hitherto seldom-reported combination of two malignant tumours with distinct and often contrasting epidemiology, histology and prognosis coexisting in the same patient.

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Case of unilateral leg swelling: a DVT mimic

A 68-year-old woman with known metastatic renal cell carcinoma presented with an acutely swollen right leg. In between the two sessions of palliative radiotherapy to the right hip, she also had right hip modified Harrington procedure for tumour resection with hip replacement. Initial clinical evaluation raised the suspicion of right leg deep vein thrombosis (DVT). However, DVT was excluded and further investigations revealed stenosis of the right external and common iliac veins, likely secondary to radiotherapy.

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Idiopathic nodular glomerulosclerosis (ING) in an African American (AA) man with hepatitis C

Idiopathic nodular glomerulosclerosis (ING) in a non-diabetic patient is uncommon. Nodular glomerulosclerosis is hallmark sign of diabetic nephropathy. ING is a very rare clinicopathological disease associated with smoking, obesity and hypertension, chronic obstructive pulmonary disease and metabolic syndrome. A 68-year-old non-obese African American man with hypertension, smoking and history of hepatitis C presented to the clinic with progressive worsening of lower extremity oedema and declining renal function over few months. Renal biopsy demonstrated nodular glomerulosclerosis. In this case, ING is hypothesised to be associated with hepatitis C along with smoking and hypertension (HTN). We present this case to speculate the existence of yet unknown aetiologies of ING.

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Everyone is valuable

This case highlights the therapeutic value of valuing our patients as people. It starts with a common challenge we can all face as doctors both in primary and in secondary care. It is the challenge of facing a situation where both patient and doctor are 'stuck' where no progress is being made in patient care. A different approach was made to the situation and both patient and doctor could move on. It highlights an issue that is relevant for 'stuck' patients and all of our patients.

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