tbuckley/cabot-search huggingface dataset:
ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer.
Authors: Paula Ghaneh, Daniel H. Palmer, Silvia Cicconi, Christopher Halloran, Eftychia Eirini Psarelli, Charlotte Louise Rawcliffe, Rajaram Sripadam, Somnath Mukherjee, Jonathan Wadsley, Ahmed Al-Mukhtar, Long R. Jiao, Harpreet Singh Wasan, Ross Carter, Janet Shirley Graham, Farooq Ammad, Jonathan Evans, Christine Tjaden, Thilo Hackert, Markus W. Buchler, John P. Neoptolemos
Journal: Journal of Clinical Oncology (2020)

4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P&lt;0.001. 9 out of the 51 neoadjuvant patients included in the safety set reported 12 serious adverse events of grade 3 or above. Conclusions: There was no difference in resection rate between arms, however neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Clinical trial information: 89500674 .
Evaluation of an individualized starting-dose of niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study.
Authors: Mansoor Raza Mirza, Antonio Gonzalez Martin, Whitney Graybill, David M. O'Malley, Lydia Gaba, Oi Wah S. Yap, Eva M. Guerra, Peter Graham Rose, Jean-Francois Baurain, Sharad A. Ghamande, Hannelore denys, Emily Prendergast, Carmela Pisano, Philippe Follana, Klaus Baumann, Paula Calvert, Jacob Korach, Yong Li, Divya Gupta, Bradley J. Monk
Journal: Journal of Clinical Oncology (2020)

6050 Background: Niraparib is approved at a fixed starting dose (FSD) of 300 mg QD for maintenance treatment of patients (pts) with recurrent ovarian cancer (OC) achieving a complete or partial response to platinum-based chemotherapy based in the ENGOT-OV16/NOVA study. A post-hoc analysis of NOVA showed baseline bodyweight (BW) and platelet count (PC) were predictive for hematologic toxicities and dose reductions. Following this analysis, the PRIMA/ENGOT-OV26/GOG-3012 study was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen. Methods: This double-blind, placebo-controlled, phase III study randomized 733 pts with newly diagnosed advanced OC with a complete or partial response to first-line (1L) platinum-based chemotherapy. The protocol was amended to change the dose from 300 mg FSD for all patients to an ISD regimen: 200 mg QD in pts with BW &lt;77 kg and/or PC &lt;150,000/µL or 300 mg QD in pts with BW ≥77 kg and PC ≥150,000/µL. Exposure, efficacy, and safety data were compared between patients treated with FSD vs ISD. Results: Efficacy in the ISD subgroup was comparable to the FSD subgroup relative to placebo (Table). An interaction test showed no treatment difference between ISD and FSD at the pre-specified 0.10 significance level ( p=0.30). Medians for dose intensity and relative dose intensity in pts who received niraparib were similar. The overall safety profile among pts in the niraparib arm (n=484), including grade ≥3 hematologic toxicities, improved with the ISD. Conclusions: The ISD in the 1L maintenance setting provides comparable efficacy to the FSD while reducing the risk of hematologic toxicities. No new safety signals were identified. Clinical trial information: NCT02655016. [Table: see text]
Preclinical evaluation of CLX-155, a novel prodrug of 5-FU for the treatment of cancer.
Authors: Sunil Kumar KB, Mahesh Kandula, Sivanesan P
Journal: Journal of Clinical Oncology (2020)

e15614 Background: CLX-155 is a novel prodrug of 5-FU, developed by adding two acetyl groups (ester bond) and a caprylic acid moiety (amide bond) to 5'-DFCR ring structure. CLX-155 is designed to have a differentiated ADME profile, with improved safety and efficacy over capecitabine. Here, we present the preclinical data of CLX-155 in comparison with capecitabine. Methods: Solubility/stability of CLX-155 was studied in buffers, simulated gastrointestinal fluids and liver microsomes. In vitro metabolite profiling in hepatocytes was done following standard protocol. An oral (gavage) dose range finding (DRF) toxicity, comparative oral pharmacokinetic study and antitumor activity in HCT-116 human colon cancer cell xenograft model was conducted in mice. DRF study in mice evaluated the toxicity of CLX-155 when administered at once daily doses of 100 to 1000 mg/kg/day for 7-days. The oral pharmacokinetics CLX-155/metabolites (5'-DFCR, 5'-DFUR and 5-FU) was determined in mice at MTD dose of 500 mg/kg and for capecitabine at 1000 mg/kg. Antitumor activity of CLX-155 was evaluated in Foxn1 athymic mice at 125, 250 and 500 mg/kg/day and for capecitabine at 1000 mg/kg/day. Treatment was performed for three consecutive weeks (5 days on; 2 days off per week). Results: The results of in-vitro studies confirmed an acceptable profile for further development of CLX-155. Maximum tolerated dose of CLX-155 in mice was 500 mg/kg/day. The key toxicity findings were consistent with the mechanism of action and comparable with capecitabine. Oral PK study in mice showed a lower plasma C max for 5'-DFCR, 5'-DFUR and 5-FU. Plasma AUCs of the metabolites were close to or higher than that of capecitabine, indicating an extended absorption or altered metabolism in comparison with capecitabine. CLX-155 caused significant, tumor growth inhibition at all the dose levels tested. Complete tumor regression was seen in 2/10 animals at 500 mg/kg/day of CLX-155. CLX-155 was better tolerated in the mouse xenograft study, no mortality in CLX-155 versus 2/10 in capecitabine group. Conclusions: CLX-155 has an excellent safety and a differentiated ADME profile in relation to capecitabine. This translated into an improved in-vivo antitumor activity for CLX-155 in the HCT 116 xenograft model in relation to capecitabine. Overall data indicate that CLX-155 could offer significant improvements over the currently approved capecitabine in terms of dose size, frequency of administration, safety and interpatient variability in pharmacokinetics.
女性腺性膀胱炎23例临床分析
Authors: 陈彤, 蒋宁
Journal: BMJ (2007)

回顾分析23例女性腺性膀胱炎患者的临床资料.全部病例经尿道电汽化术治疗后,18例症状完全消失,5例好转,其中2例分别于术后6个月、10个月复发,再次行经尿道电汽化术治疗,随访至2007年2月无复发.结果 说明,经尿道电汽化术是治疗女性腺性膀胱炎的主要治疗方法。
口对口吸出小儿气管异物一例
Authors: 林卓仪, 温小丽
Journal: BMJ (2004)

患儿男,4个月,因吞食香蕉误入气管致面色苍白,口唇、指趾甲发绀,呼吸微弱,脉搏160次/ min.立即将患儿置于空气流通处,松解衣领;指压人中、十宣穴,两穴均有醒脑开窍、止惊厥作用;对患婴行仰卧位口对口吸异物,无效,立刻改倒悬位,拍背,指重压涌泉穴,再口对口吸异物成功,患婴大声啼哭,缺氧征逐渐纠正,呼吸平稳。
住院早产儿两年病例资料分析
Authors: 梁少霞, 麦智广
Journal: BMJ (2011)

回顾分析佛山市第一医院新生儿科2009年及2001年住院早产儿的病例资料,探讨两年里住院早产儿患病情况和治疗结果变化. 一、资料与方法 从本院住院病案管理系统中调出新生儿科2009年1月1日至12月31日、2001年1月1日至12月31日出院的早产儿病例资料,由经过培训的专业人员逐一查对病历,填写早产儿调查表,并统一诊断治疗标准.分为2009年组(233例)、2001年组(133例)。
Retroperitoneal laparoscopic surgery for huge adrenal benign tumors: report of 9 cases
Authors: Shaozhong Xian, Bo Song, Xiao Han, Dawei Cai, Peishan Wu
Journal: BMJ (2017)

The clinical data of 9 patients with huge adrenal tumors (≥6 cm) undergoing retroperitoneal laparoscopic adrenalectomy between February 2015 and September 2016 were retrospectively analyzed. There were 2 males and 7 females aged 29-65 years. The tumors were detected due to investigation of paroxysmal hypertension in 4 cases, and during the health check-up in 5 cases. The lesions were located on the right side in 4 cases, on the left side in 4 cases and bilaterally in 1 case. The operations were all successful, there was no case transferring to open surgery. The average operation time was 70 min (50-100 min), mean bleeding volum was 100 ml(50-200 ml). The postoperative diagnosis: 4 cases of pheochromocytoma, 2 cases of cortical adenoma, 2 cases of neurilemmoma and 1 case of neuroinoma. The average follow-up time was 13.5 months (6-24 months) and no recurrence was found.


Key words: 
Laparoscopy; Adrenal gland neoplasms; Adrenalectomy
Distribution and drug resistance of pathogens isolated from upper and lower ureter of stone obstruction in patients with ureteral calculi
Authors: Shuaibin Wang, Youhua He, Kaiyuan Yu, Qin Feng, Wenxue Yang
Journal: BMJ (2018)

Four hundred and twenty two patients with ureteral calculi undergoing surgical treatment from January 2016 to December 2016 were enrolled in the study. Urine samples were taken from upper and lower ureter of stone obstruction, pathogen examination and drug susceptibility tests were performed. Twenty nine strains of pathogens were isolated from the upper segment of ureter with a detection rate of 6.9%; 22 strains were gram-negative bacteria (75.9%) and 3 strains were gram-positive bacteria (10.3%) and 4 strains were fungi (13.8%). Forty eight strains of pathogenic bacteria were isolated from the lower segment with a detection rate of 11.4%; 37 strains were gram-negative bacteria (77.1%), 11 strains were gram-positive bacteria (22.9%), no fungi was isolated. In 20 cases the positive results were obtained only from upper ureter urine samples, and in 39 cases the positive results were obtained only from lower segment samples. The same pathogens were detected from both upper and lower ureter of stone obstruction in 7 cases, and different pathogens were identified in 2 cases. The most common pathogens were Escherichia coli, followed by Proteus mirabilis, Klebsiella pneumoniae, Enterococcus faecalis and Enterococcus faecium. The resistance to quinolones in gram-negative bacteria was higher than that to cephalosporins. The resistance rate of Escherichia coli to cephalosporin was 36.7%-63.3%, that to ciprofloxacin and levofloxacin was 86.7%-100.0%; the resistance rate of Enterococcus to erythromycin was 100.0%. It is suggested that ureteral calculi obstruction may lead to negative culture results of conventional mid-stream urine samples. It is of clinical value to investigate the distribution and antibiotic resistance of pathogens both from upper and lower segments of ureter in patients with ureteral calculi.


Key words: 
Ureteral calculi; Ureteral obstruction; Urinary tract infections; Drug resistance
Cystic Adenoma of the Pigmented Ciliary Epithelium
Authors: Wolfgang E. Lieb, Jerry A. Shields, Ralph C. Eagle, Daniel Kwa, Carol L. Shields
Journal: Ophthalmology (1990)

A 51-year-old white man was found to have a deeply pigmented mass in the ciliary body and peripheral choroid of his right eye with an associated vitreous hemorrhage. Although the tumor appeared to be a ciliochoroidal melanoma, a melanocytoma and adenoma of the pigment epithelium also were considered in the differential diagnosis. The tumor was removed by a large partial lamellar sclerocyclochoroidectomy. Results of histopathologic evaluation showed a cystic adenoma of the pigmented ciliary epithelium. To the authors' knowledge, this was the first immunohistopathologic study of this tumor. Results of the study showed marked immunoreactivity for low molecular weight cytokeratins, vimentin, and S-100 protein. These immunohistochemical studies are consistent with the origin of this tumor from pigment epithelial cells.
A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer.
Authors: Joyce F. Liu, Mark F. Brady, Ursula A. Matulonis, Austin Miller, Elise C. Kohn, Elizabeth M. Swisher, William P. Tew, Noelle Gillette Cloven, Carolyn Muller, David Bender, Richard G. Moore, David Paul Michelin, Steven E. Waggoner, Melissa Ann Geller, Keiichi Fujiwara, Stacy D. D'Andre, Michael Carney, Angeles Alvarez Secord, Katherine M. Moxley, Michael A. Bookman
Journal: Journal of Clinical Oncology (2020)

6003 Background: Combination cediranib (C) and olaparib (O) improved progression-free survival (PFS) in patients (pts) with relapsed platinum (plat)-sensitive high-grade ovarian cancer (ovca) compared to O alone in a Phase 2 trial (NCT01116648). We conducted this randomized, open-label Phase 3 trial (NCT02446600) to assess whether combination C+O, or O alone, was superior to standard of care (SOC) plat-based therapy in relapsed plat-sensitive ovca. Methods: Eligible pts had recurrent plat-sensitive [ &gt; 6-month plat-free interval (PFI)] high-grade serous or endometrioid, or BRCA-related, ovca. One prior non-plat therapy and unlimited prior plat-therapies were allowed; prior anti-angiogenics in the recurrent setting or prior PARP inhibitor were exclusions. Pts were randomized 1:1:1 to SOC (carboplatin/paclitaxel; carboplatin/gemcitabine; or carboplatin/liposomal doxorubicin), O (300mg twice daily), or C+O (C 30mg daily + O 200mg twice daily). Randomization was stratified by g BRCA status, PFI (6-12 vs &gt; 12 months), and prior anti-angiogenic therapy. Target sample size was 549 pts; primary analysis occurred 2 years after the last pt enrolled. The primary endpoint was PFS. Type 1 error = 0.025 was controlled by a gatekeeping hierarchy that assessed C+O vs SOC, then O alone vs SOC, and finally C+O vs O. All maintenance therapy was prohibited. Results: Between 4FEB2016 and 13NOV2017, 565 pts enrolled (187 SOC, 189 O, 189 C+O), and 528 pts initiated treatment (166 SOC, 183 O, 179 C+O). 23.7% of patients had g BRCAmut. Median follow-up was 29.1 months. 53 pts on SOC initiated non-protocol therapy (predominantly PARP inhibitor maintenance) before disease progression. The hazard ratio (HR) for PFS was 0.856 (95% CI 0.66-1.11, p = 0.08, 1-tail) between C+O and SOC and 1.20 (95% CI 0.93-1.54) between O and SOC, with median PFS of 10.3, 8.2, and 10.4 months for SOC, O, and C+O, respectively. Response rates were 71.3% (SOC), 52.4% (O), and 69.4% (C+O). In gBRCA pts, HR for PFS was 0.55 (95% CI 0.73-1.30) for C+O vs SOC, and 0.63 (95% CI 0.37-1.07) for O vs SOC. In non-g BRCA pts, HR for these comparisons was 0.97 (95% CI 0.73-1.30) and 1.41 (1.07-1.86). No OS differences between arms were observed at 44% events. Pts receiving C+O (vs SOC) had more frequent Grade 3 or higher gastrointestinal (30.1% vs 8.4%), hypertension (31.7% vs 1.8%), and fatigue events (17.5% vs 1.8%). Conclusion: C+O demonstrated similar activity to SOC in relapsed plat-sensitive ovca but did not meet the primary endpoint of improved PFS. Clinical trial information: NCT02446600.
The association between tonsillectomy and Hodgkin’s lymphoma: A systematic review and meta-analysis.
Authors: Anas Albawaliz, Zainab Fatima, Abdulrahman Abonofal, Abdelrhman Abumoawad, Laith Al Momani, Anuj Shrestha
Journal: Journal of Clinical Oncology (2020)

e20015 Background: Several observational studies have evaluated tonsillectomy as a predisposing factor for developing Hodgkin’s lymphoma (HL) with contradicting results. The true association is unknown. We sought to systematically review the literature and perform the first meta-analysis to study the association between a history of tonsillectomy and the development of HL. Methods: A systematic review was conducted in Pubmed, and Cochrane databases from inception through January 2020 to identify the studies which explored the association between history of tonsillectomy and HL. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird and a pooled odds ratio (OR) was calculated. A forest plot was generated, and publication bias was assessed for using conventional techniques. Results: Twenty studies with a total of 17931 patients were included in our analysis. 6231 of the patients were diagnosed with HL. The pooled OR for the development of HL in patients with history of tonsillectomy was 1.237 (CI 1.075-1.424, P = 0.003, I 2 = 45.073%) compared to patients without a history of tonsillectomy. Conclusions: Our analysis shows a statistically significant association between a history of tonsillectomy and the development of HL. As all the studies included in our meta-analysis were observational, we need prospective studies to better understand this important association.
抗-e引起的输血相关性溶血一例及文献复习
Authors: 武希润, 王琦, 王玲, 王晋萍, 左江清
Journal: BMJ (2008)

抗-e是较为罕见的Rh血型抗体,多由反复输血或妊娠诱发,机体再次受到同种异型抗原刺激时,将出现免疫回忆反应,导致输血相关性溶血.现报道1例抗-e引发的输血相关性溶血,并复习有关文献。
Prostate cancer outcomes by ESRD status.
Authors: Nagaraju Sarabu, Weichuan Dong, Al Ray, Austin Fernstrum, Lee Evan Ponsky, Siran M. Koroukian
Journal: Journal of Clinical Oncology (2020)

e17513 Background: Persons with end-stage renal disease (ESRD) comprise a vulnerable subgroup of the population. Yet, rarely have studies on cancer disparities accounted for ESRD status. We sought to compare prostate cancer stage at diagnosis, treatment, and outcomes among men with and without ESRD. Methods: Utilizing SEER-Medicare database between years 2000-2016, we retrieved sociodemographic variables, including age (40-54, 55-64, 65-74, and 75+), race (African American vs. all others), marital status (married/partnered vs. all others), residence in a census tract with poverty rate &gt; 20%; cancer stage at diagnosis (local, regional, distant, and unknown); treatment (surgery and radiation therapy); and overall and cancer specific survival (OS and CSS) from the SEER, and ESRD status preceding prostate cancer diagnosis from the Medicare portion of the file. In addition to descriptive analysis, multivariable survival analysis was utilized to evaluate the association of ESRD status with OS and CSS after adjusting for patient covariates. Results: Our study population included 2,922 ESRD and 600,848 non-ESRD men diagnosed with incident prostate cancer during the study period. A disproportionately higher percentage of ESRD patients were in the 40-54 age group compared to non-ESRD (9.7 vs 3.6%). Similarly, the percentage of prostate cancer patients who were African American was 41.5% among ESRD patients, compared with 14.4% in their non-ESRD counterparts. In addition, more ESRD than non-ESRD patients lived in census tracts with poverty rates greater than 20% (31.2% vs. 18.0%). With regard to stage, 10.6% of ESRD patients but only 4.5% of non-ESRD patients were diagnosed with distant-stage disease; and while only 24.8% of ESRD patients underwent surgery, 36.9% of non-ESRD patients did so. The rate of radiation therapy was similar across the two groups. Multivariable survival models showed that, adjusting for patient covariates, ESRD status was associated with unfavorable OS and CSS (adjusted hazard ratio (AHR): 4.00 (95% confidence interval: 3.82, 4.18), and AHR: 1.54 (1.37, 1.73), respectively). Median follow up was 3.35 and 7.13 years between the ESRD and non-ESRD cohorts. Conclusions: ESRD status in prostate cancer patients is associated with marked sociodemographic and economic disparities. Compared to their non-ESRD counterparts, more ESRD patients are diagnosed with advanced-stage disease, are less likely to undergo surgery, and experience shorter overall and cancer-specific survival. Future studies should be directed to gain insight into factors contributing to unfavorable cancer-specific outcomes.
Immune-related adverse events and outcomes during treatment with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) patients.
Authors: Javier López Gallego, Pablo Ayala de Miguel, Itziar Gorospe García, Pablo René Rivera Vargas, Andrea Posada Restrepo, Jonathan Aires Machado, Rubén Alonso Calderón, José Manuel Rodríguez García, Eduardo Ceballos Barbancho, Alfonso Acero Caballero, Andrea Illán Varella, Laura Quintana Cortés, Pablo Borrega Garcia
Journal: Journal of Clinical Oncology (2020)

e21662 Background: Immunotherapy of cancer has changed the paradigm of treatment of many tumours, specially non-small cell lung cancer (NSCLC). The use of immune-checkpoint inhibitors (ICI) is associated in some patients with the development of new immune-related adverse events (irAEs). Our aim was to study if there is any correlation between the appearence of irAEs and the efficacy of ICI. Methods: We collected data of 104 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and December 2019. Several variables as clinical, tumour-related and therapeutical were included and univariate and multivariate Cox regression analysis were performed. Results: Cohort of 84 men and 20 women, median age of 67 years and 86% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 89% were active or ex-smokers and 11% had never smoked. 60% of patients had adenocarcinoma histology, 39% scamous and 1% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 37% M1a, 30% M1b and 30% M1c. 2 patients had driver mutations in EGFR gene. 41% of patients had unknown PDL1 status; 14% had no PDL1 expression, 14% low expression and 31% high expression. 78% of patients had progressed to prior line of treatment, while 22% were treatment-naive. irAEs occured in 65% of patients; 12% developed grade 3 to 4 toxicities. More frequent irAEs were fatigue (54%) and rash (27%). Significant statistical variables in univariate analysis were included in multivariate analysis by Cox regression. The appearence of any grade of iRAE was associated with improved progression-free survival (PFS) (median 17.9 months vs 5.1 months; HR 7.12; p = 0.008). Those patients who experimented any grade of irAE were more likely to achieve stabilization or response than those who suffered progression of disease (HR 13.00; p &lt; 0.001; 95% CI [3.47-48.78]. The use of corticosteroids during treatment with ICI was not related to the benefit of treatment. Conclusions: Appearence of immune-related adverse effects during treatment with ICI was associated with better outcomes in our population. The use of corticosteroids during immunotherapy didn´t have any deleterious effect on the efficacy of treatment.