tbuckley/cabot-search huggingface dataset:
Winged scapula in breast cancer patients after sentinel lymph node biopsy: A longitudinal cohort study.
Authors: Luiz Felipe Nevola Teixeira, Fabio Sandrin, Cristina Garusi, Mario Rietjens, Viviana Galimberti, Fabio Bassi, Andrea Manconi, Sara Gandini, Maria Claudia Simoncini, Paolo Veronesi
Journal: Journal of Clinical Oncology (2016)

10085 Background: Sentinel lymph node biopsy (SLB) has been the most performed diagnostic procedure aimed at assessing nodal metastatic, helping to avoid axillary dissection (AD), which could lead to post-surgical sequelae. Data regarding complications of SLB shows that the procedure is not risk–free. However, there is still a lack of information on incidence and prognosis. Our study were conducted to determine the incidence of winged scapula (WS) in patients who underwent SLB and search for predictive factors. Methods: Our study were conducted from May 2013 to June 2014, enrolling patients who underwent breast cancer surgery, at the European Institute of Oncology (EIO). After signing the consent form, patients were assessed prior to surgery and those who had undergone SLB without AD were included. Patients eligible for plastic surgery with flaps were excluded. Postoperative physical assessment was conducted one day after surgery, at discharge and at six months after surgery. Results: We enrolled 945 patients with a total of 1031 axillary surgeries; 613 (59,5%) SLBs were included in our analysis. Of these, 258 (42%) underwent plastic reconstruction. Mean age was 53 years (SD = 11.6). A total of 33 patients presented winged scapula postoperatively with an incidence of 5% (95% CI = 4-7%), 9% among patients with plastic reconstruction and 2% among SLB. Tumor stage (p = 0.04) mastectomy (p = 0.006), reconstructive surgery (p = 0.0005), and reconstructive technique with the complete pocket with serratus anterior (p = 0.04) were significantly associated with WS. Multivariate analyses confirmed that plastic surgery increases the risk of WS (p = 0.02; OR = 2.88 with 95%CI: 1.20-6.91). All 33 patients presented winged scapula during hospital discharge and 4 (12%) after 6 months. Conclusions: Incidence of WS is small in patients who undergo SLB and breast reconstruction with a complete pocket may increase the risk. We recommend that post-surgical evaluation be performed in SLB patients, as the assessment is non-invasive and does not incur extra costs. Even with a small incidence, information about the sequela, exercise prescription and assessment should be imparted to these patients, enhancing their empowerment and rehabilitation.
Is It Time to Reconsider the Milan Criteria for Selecting Patients With Hepatocellular Carcinoma for Deceased‐Donor Liver Transplantation?
Authors: Charlotte E. Costentin, Yanik J. Bababekov, Andrew X. Zhu, Heidi Yeh
Journal: Hepatology (2018)

Liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC) because it removes tumor as well as the underlying cirrhotic liver. Because of a global organ shortage, LT for patients with HCC is limited to patients with expected survival comparable to that of nonmalignant indications. Therefore, identifying patients with lower rates of HCC recurrence and higher rates of survival is critical. International guidelines have considered the Milan Criteria (MC) the standard for selecting patients with HCC for deceased-donor LT (DDLT). However, several alternative criteria have been reported in the Western world. Interestingly, the two most recent models combining α-fetoprotein level, number of nodules, and size of the largest nodule have been shown to outperform MC in identifying patients with low risk of HCC recurrence or those who will survive for 5 years after liver transplantation. In addition, new models overcome limitations of MC in improving classification of high- versus low-risk patients with HCC for DDLT. These recent scoring systems also provide clinicians with user-friendly tools to better identify patients at lower risk of recurrence. Conclusion: Although most Western countries still select patients based on MC, there is a mounting change in recent practice patterns regarding the selection of patients with HCC for DDLT. Herein, we describe how alternative criteria should lead to reconsideration of MC as it applies to selecting patients with HCC for DDLT in international guidelines.
The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder
Authors: Chadi G. Abdallah, Lynnette A. Averill, Teddy J. Akiki, Mohsin Raza, Christopher L. Averill, Hassaan Gomaa, Archana Adikey, John H. Krystal
Journal: The Annual Review of Pharmacology and Toxicology (2018)

New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stress-related synaptic dysconnectivity in the neurobiology and treatment of PTSD. Here, we integrate this perspective within a broader framework-in other words, a dual pathology model of ( a) stress-related synaptic loss arising from amino acid-based pathology and ( b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy.
Stromal infiltrating CD8+ and CD20+ lymphocytes and CD204+ M2 macrophages but not PD-L1 expression on tumor cells are prognosticators for patients with resectable thymic carcinoma.
Authors: Jun Sato, Noriko Motoi, Shigehisa Kitano, Noboru Yamamoto, Shunichi Watanabe, Yuichiro Ohe, Nobuyoshi Hiraoka
Journal: Journal of Clinical Oncology (2017)

e20002 Background: Thymic carcinoma (TMCA) is a rare malignant disease, and standard systemic chemotherapy has not been established. Tumor microenvironment (TME) that consists of tumor cells (TCs), tumor-infiltrating immune cells (TIICs) and stromal cells is thought to be an important biological feature of cancer behavior. The aim of this study was to analyze TME of TMCA, focusing the TIICs’ characteristics and the PD-L1 expression in the TC and TIIs and their impact on the clinical outcome. Methods: Fifty-one TMCA specimen with median observation period 33.8 months (range: 0.2-351) were collected. We evaluated the immunohistochemical profile of TIIs using antibodies against CD8, CD20 and FoxP3 for TIICs, CD204 for tumor-associated macrophages (TAMs), and PD-L1(SP142) expression of both TIICs and TCs using representative FFPE specimen. The density (median positive cell number per 1 mm 2 ) of TIICs or TAMs was evaluated in intraepithelial (IE) and tumor stromal (TS) areas separately by using an automated image analyzer. Statistical analysis was performed using SPSS (version 24) and used p &lt; 0.05 as significant level. Results: 51.9% (n = 26) had recurrent disease, and 31% (n = 16) survive without tumor. Of recurrent group, the density of CD8 + (54.5 vs 432) and CD20 + (35.9 vs. 516) TIIs, as well as the CD8 + /CD204 + , CD20 + /CD204 + ratio in TS were significantly lower and FOXP3 + (590 vs 176) in TS was higher than that of non-recurrent group (Mann-Whitney U-test, two-sided). In the IE area, the lower CD20 + /CD204 + ratio associated with recurrence. The CD20 and FOXP3 TIIs in TS also associated with the overall survival. There was no significant association between CD204 or PD-L1 expression and patients’ outcome. Conclusions: Our retrospective study showed the density of CD8 + , CD20 + and FOXP3 + stromal-infiltrating lymphocytes and CD204 + M2 macrophage were prognostic factors for patients with resectable TMCA. Host immune reaction in TME might be one of the important prognostic factors for TMCA.
P01.166 Survival with pineal region tumours - Is the outlook changing?
Authors: P Nanda, J Duffin, P Kane, A Varma
Journal: Neuro-Oncology (2018)

Tumours in the pineal region is a rare entity and in general considered to have a poor outcome. We analysed a series of patients with pineal region tumours and found them to have on an average a longer life expectancy and a lesser rate of recurrence as compared to patients with cerebral tumours outwith pineal region. Retrospective study of 13 patients with histologically proven pineal tumours treated in our neurosurgical unit between 2002 and 2017. Data were collected from case notes, histopathology reports, clinic letters, MDT outcomes and from oncology department. Thirteen patients with pineal tumours treated in our unit since 2002 had tumours representing all possible differentiations/grading. There were two patients with pineal glioblastomas (Gr IV), two with pineoblastoma (Gr IV), three patients with pineal parenchymal tumours of intermediate differentiation (Gr II or III), two astrocytomas (Gr II and III), two pineal germinomas (Gr I), one pineocytoma and one pineal papillary neuroepithelial tumour. Majority of these (10/14) had biopsy whereas four underwent debulking of pineal tumour but all of them received radiochemotherapy after surgical procedure and four had subsequent adjuvant chemotherapy. Two patients did not survive but the remaining have had long term survival since diagnosis. Even importantly three of the four patients diagnosed with high grade pineal tumours (GBM and pineoblastoma) have had better outcome amongst the cohort. In this analysis, most of the patients had reasonably good outcome, especially patients with high grade pineal tumours. The two pineal glioblastomas are surviving with good performance status and radiological evidence of no recurrence at 78 months and 56 months from the time of diagnosis. Is this a result of advanced targeted radiochemotherapy or due to the anatomic location of pineal gland which makes the tumours sensitive to treatment or perhaps pineal region tumours are encapsulated and do not disseminate via white matter channels. This needs further research. We appreciate that with a study involving a small number of patients, we cannot generalise the outcome in all pineal tumours but we would like to run a multicentral research to look into the peculiar outcome of pineal tumours.
Abstract 13534: Mechanisms of Low-intensity Isometric Electrical Stimulation Under Moderate Blood Flow Restriction on Muscle Hypertrophy in a Rat Model: Involvement of Muscle Partial Oxygen Pressure
Authors: Toshiaki Nakajima, Tomohiro Yasuda, Shotarou Obi, Shigeru Toyoda, Teruo Inoue, Yutaka Kano
Journal: Circulation (2017)

Introduction: Mechanical stress is a main factor that enhances the protein synthesis, but exercise training under moderate blood flow restriction (MBFR) elicits muscle hypertrophy despite a low-intensity load that resembles high-intensity exercise. Hypothesis: The aim of the present study is to create a rat exercise model under MBFR, and clarify the hypothesis that the muscle hypoxia and exert tension level determine the protein synthesis pathways, muscle hypertrophy, and mitochondria associated proteins. Methods: Wistar rats wore the cuff to restrict muscle blood flow under anesthesia. The blood flow restriction (80 mmHg) was added by wearing a cuff on the thigh of the rat, and low-intensity isometric contraction (LIES, 30Hz) due to electrical stimulation to the tibialis anterior muscle was loaded. The oxygen partial pressure and the exerting tension were evaluated. The muscles stimulated with the same protocol were excised 3 h later and the phosphorylation response of the mTOR signaling pathway was exam...
Advanced signet ring cell type gastroesophageal cancers in Central American patients age 40 and below: A summary of one tertiary care center's experience and a review of the literature.
Authors: Timothy Lewis Cannon, William B. Ershler, Lana Bijelic, Amanda Nizam, Neda Hosseini
Journal: Journal of Clinical Oncology (2017)

e15515 Background: Gastric Cancer mortality rates in Central and South America are among the highest in the world. Our institution has monitored a cohort of patients who have presented with metastatic gastroesophageal cancer, age 40 or below. Methods: After observing multiple cases of advanced gastric cancer in young immigrants from Latin America, we performed a retrospective cohort study at Inova Fairfax Hospital, a 1000 bed tertiary care center in Northern Virginia. We reviewed our cancer registry from 2013-2016, to identify all patients, age 40 or below, with stage IV gastric adenocarcinoma. We also reviewed the percentage of hispanic patients in our cancer registry for all cancer diagnoses, for comparison. Results: There were thirteen patients with stage IV gastric cancer who were aged 40 or below found in our registry. Ten of the thirteen patients (76.9%) were from Latin America (see Table 1), with the majority of those being from either El Salvador or Honduras. All thirteen cases were notable for signet ring cell differentiation. Hispanic patients make up only 8.3% of the total subjects and 12.9% of gastric cancer subjects in the Inova Fairfax Hospital Cancer registry during that same time period. Conclusions: Stage IV signet ring cell gastric cancers have occurred frequently at our tertiary care center among young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]
Risk factors and prognostic impact of venous thromboembolism (VTE) in patients (pts) with advanced gastric cancer (AGC).
Authors: Hiroyuki Arai, Shuichi Hironaka, Keiko Minashi, Tadamichi Denda, Mototsugu Shimokawa, Taketo Yamaguchi
Journal: Journal of Clinical Oncology (2016)

e15521 Background: AGC and chemotherapy are associated with a high incidence of VTE. Risk factors of VTE in AGC pts receiving chemotherapy, and prognostic impact of VTE on their survival are not well-known. Methods: The subjects of this retrospective cohort study were 283 pts who started 1st-line chemotherapy for AGC from Sep. 2009 to Jul. 2015 at Chiba Cancer Center, Chiba, Japan. VTE was defined as deep vein thrombosis and/or pulmonary embolism diagnosed with enhanced CT scan. No pts had a central venous catheter for infusion of anticancer agents. Pts diagnosed with VTE received warfarin or edoxaban as anticoagulant therapy for at least 6 months. Cumulative incidence of VTE and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess the relationship among VTE, OS, and covariates (clinicopathological characteristics at baseline). Results: Patient characteristics were as follows: age median (range), 66 (24-85); male/female, 203/80; PS 0-1/2-3, 262/21; histology intestinal/diffuse/mucinous, 106/169/8; peritoneal metastasis ±, 158/125; BMI ≥ 25/ < 25, 39/244. As of Dec. 2015, VTEs were observed in 39 (13.8%) pts. The cumulative incidence of VTE at 6-month/1-year was 9.5%/14.8%. In univariate analysis, female, diffuse type, peritoneal metastasis +, liver metastasis -, and BMI ≥ 25 were associated with the occurrence of VTE (p < 0.10). Multivariate analysis including those covariates showed BMI ≥ 25 (HR = 3.35; 95% CI, 1.72-6.55; p < 0.01) and peritoneal metastasis + (HR = 1.96; 95% CI, 1.00-3.83; p < 0.05) were the independent risk factors of VTE. Median OS in pts with/without VTE was 13.4/12.1 months (Log-rank test: p = 0.30). After adjusted by other prognostic factors (PS [0-1/2-3], primary site [stomach/esophagogastric junction], number of metastatic sites [0-1/ ≥ 2], peritoneal metastasis [±], bone metastasis [±]), VTE had no impact on OS (HR = 0.72; 95% CI, 0.49-1.04; p = 0.08). Conclusions: BMI ≥ 25 and presence of peritoneal metastasis could be risk factors of VTE, and occurrence of VTE had no impact on OS, in AGC pts who received systemic chemotherapy.
Remodeling tumor-associated macrophages with a CD47xMesothelin bispecific antibody for efficient elimination of solid tumor cells.
Authors: Walter G. Ferlin, Vanessa Buatois, Krzysztof Masternak, Limin Shang, Stefano Majocchi, Eric Hatterer, Xavier Chauchet, Marie H. Kosco-Vilbois, Nicolas Fischer
Journal: Journal of Clinical Oncology (2018)

e15126 Background: Mesothelin (MSLN) is a cell surface glycoprotein associated with poor prognosis in many cancers, with elevated soluble MSLN (sMSLN) serum levels considered a biomarker of disease severity. Monoclonal antibodies (mAbs) targeting MSLN have demonstrated limited clinical efficacy. CD47, a checkpoint for innate immune cells, provides a ‘don’t eat me’ signal allowing healthy cells to limit elimination by phagocytes. High CD47 expression correlates with poor prognosis yet mAbs blocking CD47 are hindered by CD47’s ubiquitous expression. We developed a bispecific antibody (biAb) that: 1. targets checkpoint inhibition to the tumor via a high affinity anti-MSLN arm, and 2. avoids binding to non-cancer cells by an anti-CD47 arm of an optimized affinity. Methods: BiAbs coupling MSLN-targeting arms with a CD47-targeting arm were tested in antibody dependent cellular phagocytosis (ADCP) in vitro and xenograft tumor models. Human tumor cell lines used: NCI-N87 (gastric), HPAC (pancreatic), OVCAR-3 and Caov-3 (ovarian) and MSLN-transfected HepG2 (hepatic). Results: MSLNxCD47 biAbs significantly enhance macrophage-mediated ADCP of NCI-N87, HPAC, OVCAR-3 and Caov-3 as compared to the anti-MSLN mAb, Amatuximab. As compared to Amatuximab, the impact of sMSLN on biAb activity is limited. In a hepatic xenograft tumor model, MSLN/CD47 biAbs significantly control tumor growth, while Amatuximab and B6H12, an anti-CD47 mAb, demonstrate minimal anti-tumor activity. Tumor control in vivo is also observed for ovarian and gastric tumor cell lines. Dissecting the mechanism affording tumor control in vivo, macrophages are mobilized into the tumors in MSLN/CD47 biAb treated mice as compared to the isotype control. These recruited macrophages were shown to be critical for control of tumor growth. Conclusions: MSLN/CD47 targeting biAbs potentially offer a superior strategy to MSLN-targeted mAbs in managing solid tumors by remodeling the immune phenotype of the tumor microenvironment.
Bendamustine with ixazomib and dexamethasone (BID) for double refractory relapsed multiple myeloma (RRMM): Phase I safety and dosing results.
Authors: Binod Dhakal, Anita D'souza, Mehdi Hamadani, Carlos Eduardo Arce-Lara, Katrina Schroeder, Katelyn Gauger, Karen Crone, Marcelo C. Pasquini, Saurabh Chhabra, Parameswaran Hari
Journal: Journal of Clinical Oncology (2017)

8012 Background: Bendamustine has promising activity in RRMM. This phase I (NCT02477215) study assessed the overall safety and activity of the combination of bendamustine with ixazomib &amp; dexamethasone in pts. with MM pts. refractory to proteasome inhibitors and IMIDs. Methods: Design: Open label dose escalation (3+ 3 design) Doses: Bendamustine at escalating doses of 70, 80 and 90 mg/m 2 on days 1,2 of each cycle with weekly ixazomib (4mg) and dexamethasone (40 mg) on days 1,8, 15 in 28-day cycles for up to 8 cycles in responders and 4 cycles if no anti-MM response. Primary end point was safety, maximum tolerated dose (MTD) and the recommended phase II (RP2D) dose. Results: As of Jan 2017, the phase I portion is complete (N= 15). The median age was 67 years with 5 (range: 2-10) median number of prior therapies. Prior therapies included bortezomib (100%), lenalidomide (100%), carfilzomib (47%), oprozomib (7%), thalidomide (7%), pomalidomide (7%) and 87% autotransplant. Five (33%) pts. completed their planned courses of therapy (4 or 8 cycles) and 3 (20%) continued on active therapy. Seven (47%) pts. discontinued study treatment (6 related to disease progression). Grade 3/ 4 adverse events were: lymphopenia (67%), neutropenia (27%), thrombocytopenia (33%), decreased WBC counts (13%), hematuria (7%), diarrhea (7%), anemia (7%), lung infection (7%), and skin ulceration (7%). Three (20%) pts. died of myeloma progression. In dose cohort 3 (bendamustine 90 mg/m2), 2 /6 pts. developed hematologic DLTs (neutropenia and thrombocytopenia) meeting MTD; RP2D was determined to be 80 mg/m2. The table below shows responses among pts receiving at least 2 cycles. The median duration of response was not reached at median follow up of 8 months (range, 4-13+) in responders. Conclusions: BID has an acceptable safety profile and a promising ORR of 45% and CBR of 73% in pts. with advanced double refractory MM. Clinical trial information: NCT02477215. [Table: see text]
TCT-645 Assessment of Angiographic Outcomes after Cangrelor in Acute Coronary Syndrome Patients with TIMI Grade Flow 0 or 1 and thrombus compared to Glycoprotein IIb/IIIa Inhibitors
Authors: Alexandre Hideo-Kajita, Toby Rogers, Hector Garcia-Garcia, Kyle Buchanan, Micaela Iantorno, Deepakraj Gajanana, Yuichi Ozaki, Kazuhiro Dan, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2018)
Identifying sexual orientation in the medical record: A first step towards understanding gynecologic cancer disparities.
Authors: Emeline Aviki, Marina Stasenko, Sarah E Dilley, William P. Tew, Don S. Dizon, Peter Bach, Carol L. Brown
Journal: Journal of Clinical Oncology (2018)

e18641 Background: Despite a known association between sexual minorities and worse health outcomes, there are no data addressing the impact of sexual orientation (SO) on ovarian cancer outcomes. Currently, no large, population-based data sets include SO, and it is unknown if SO can be reliably identified in medical records. We sought to determine if SO could be retrospectively identified in the records of ovarian cancer patients and if there are factors that impact the reporting of this information. Methods: We identified all patients undergoing a primary debulking surgery for FIGO stage IIIB-IV ovarian cancer at a cancer center from 1/2011 to 12/2013. Data were collected from the initial visit note entered by the primary provider. SO was identified by patient self-report or inferred through gender pronouns used to describe relationship status. Provider type, physician gender, and note format (templated vs free text) were collected. The appropriate statistical tests were used. Results: Of the 281 patients included, 217 (77.2%) had SO recorded or inferred from relationship status pronoun. Five (1.8%) lesbian patients were identified. There was a significant difference in whether SO was discernible based on relationship status (p < 0.01), with single patients the least likely to have SO identifiable (Table). There was no difference in the presence of SO by provider type (p = 0.78) or by physician gender (p = 0.55). The use of templated notes was associated with higher rates of discernible SO (65.6% vs 37.6%; p < 0.01). Conclusions: Our results suggest that using templated notes could result in higher and more accurate identification of patient SO, which is an important first step towards identifying potential cancer health disparities experienced by women currently underrepresented in gynecologic cancer research. Table. Variables associated with identification of sexual orientation (SO) Sexual Orientation Present Sexual Orientation Absent P-value Relationship status < 0.01 Married 187 (94.0) 12 (6.0) Partnered 8 (80.0) 2 (20.0) Widowed 12 (50.0) 12 (50.0) Divorced 7 (29.2) 17 (70.8) Single 3 (16.7) 15 (83.3) Note Type < 0.01 Templated (n = 224) 147 (65.6) 77 (34.4) Free text (n = 330) 124 (37.6) 206 (62.4)