tbuckley/cabot-search huggingface dataset:
Laparoscopy-assisted anterior resection with prolapsing technique for low rectal cancer
Authors: Xiao-jun Tang, Li-qun Pang, Yao Zhao
Journal: BMJ (2011)

Nineteen patients with low rectal cancer underwent laparoscopy-assisted anterior resection with prolapsing technique for sphincter preservation.The clinical data were retrospectively reviewed.Fecal continence was preserved successfully in all patients.There was no perioperative mortality,only two cases with anastomotic leak and one case with local recurrences.Laparoscopy-assisted anterior resection with a prolapsing technique for low rectal cancer is safe procedure and can be an alternative sphincter-preserving operation.

Key words: 
Rectal neoplasms; Laparoscopy
Clinicopathological features and treatment of bilateral asynchronous breast cancer: report of 13 cases
Authors: Junfeng Hu, Chao Hu, Ming Li
Journal: BMJ (2017)

Objective
To analyze the clinicaopathological features and treatment of bilateral asynchronous breast cancer.


Methods
The clinical and pathological data of 13 patients with bilateral asynchronous breast cancer admitted in our hospital from 2010 to 2016 were retrospectively reviewed.


Results
The bilateral asynchronous breast cancer accounted for 1.7% of all breast cancer patients admitted in the same period (13/782). The median age of patients at first onset was 47. The modified radical operation was the main surgical modality (12/13 for the first cancer; 8/13 for the second cancer). The clinical stage Ⅱ was predominant in all patients (10/13 of the first cancer; 9/13 of the second cancer). Invasive ductal cancer was the most common pathologic type (in 11/13 of the first cancer; 11/13 of the second cancer). Hormone receptors were highly expressed in most of the cases (9/13 of the first cancer; 7/13 of the second cancer). The disease-free interval was more than 10 years in most cases (8/13). Among 13 cases local recurrence was detected in 1 case, distant metastases in 2 cases, and 1 case died from distant metastasis.


Conclusion
The bilateral asynchronous breast cancer has a low incidence; however, a close follow up is necessary for early detection and treatment of the second carcinoma.


Key words: 
Breast neoplasms; Neoplasms, multiple primary; Pathology conditions, signs and symptoms; Treatment outcome
Consumption of spicy foods and total and cause specific mortality: population based cohort study
Authors: 吕筠, 祁禄, 余灿清, 杨玲, 郭彧, 陈怡平, 卞铮, 孙点剑一, 杜建伟, 格鹏飞, 唐振柱, 侯伟, 李艳杰, 陈君石, 陈铮鸣, 李立明, 代表中国慢性病前瞻性研究协作组
Journal: BMJ (2016)
Molecular dissection of normal karyotype acute myeloid leukemia.
Authors: Jacob Tyler Shreve, Manja Meggendorfer, Sudipto Mukherjee, Wencke Walter, Stephan Hutter, Ahed Makhoul, Cassandra M. Kerr, Nathan Radakovich, Hassan Awada, Yasunobu Nagata, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal Jha, Jaroslaw P. Maciejewski, Claudia Haferlach, Mikkael A. Sekeres, Torsten Haferlach, Aziz Nazha
Journal: Journal of Clinical Oncology (2020)

7534 Background: Conventional cytogenetics remain one of the most important prognostic factors in acute myeloid leukemia (AML), though 50-60% of patients (pts) have normal karyotype (NK), conventionally classified as intermediate-risk, and have very heterogeneous outcomes. A fraction of mutations such as NPM1, FLT3-ITD, and CEBPa can improve risk stratification for some pts but underestimate the molecular complexity and interactions between these genes and others. Methods: Genomic and clinical data of 2,793 primary AML (pAML) pts were analyzed. A panel of 35 genes that are commonly mutated in AML and myeloid malignancies and have shown to impact OS was included. Correlation of each mutation with others and their impact on OS were evaluated. OS was calculated from the date of diagnosis to date of death or last follow-up. Results: Of 2,793 pts with pAML, 1,352 (48%) had NK and were included in the final analysis. The median age was 55 years (range, 18-93). The median number of mutations/sample was 3 (range, 0-7). The most commonly mutated genes were: NPM1 (49%), DNMT3A (37%), FLT3-ITD (24%), CEBPa (19%), TET2 (17%), IDH2 (17%), and RUNX1 (15%). In univariate Cox regression analysis, mutations in NPM1 (HR 0.81, p =0.008), and CEBPa (single mutant, HR 0.8, double mutant, HR 0.69, p&lt; 0.001, respectively) were associated with longer OS, while mutations in DNMT3a (HR 1.26, p =0.003), FLT3-ITD (HR 1.49, p&lt; 0.001), TET2 (HR 1.26, p =0.02), RUNX1 (HR 1.36, p =0.003), SRSF2 (HR 1.58, p &lt;0.001), IDH1 (HR 1.29, p &lt;0.001), and ASXL1 (HR 1.89, p &lt;0.001) were associated with shorter OS. A total of 67% of pts had NPM1, DNMT3A, and FLT3-ITD mutated alone or in combination with each other. The median OS for pts with NMP1 Mut / DNMT3A WT /FLT3-ITD WT was 99.1 months(m), NMP1 Mut /DNMT3A Mut /FLT3-ITD WT 54.8m, NMP1 Mu t /DNMT3A WT /FLT3-ITD Mut 42.3m, NMP1 Mut /DNMT3A Mut /FLT3-ITD Mut 13.4m, NMP1 WT /DNMT3A Mut /FLT3-ITD Mut 13.1m, and NMP1 WT /DNMT3A WT /FLT3-ITD WT (triple negative) 32.7m. The median OS for pts with 0-2 mutations/sample was 59.3m, compared to 34.1m for pts with 3-4 mutations, and 16.1m for pts with &gt; 5 mutations ( p&lt; 0.001). Conclusions: We propose a simplified and robust approach to risk stratify AML pts with NK based on the mutational status of NPM1, DNMT3A, FLT3-ITD (alone or in combination with each other), CEBPa, and the number of mutations/sample.
EARLY real-world treatment and dosing patterns of ribociclib for metastatic breast cancer (mBC): A retrospective observational study.
Authors: Sanjeev Balu, Joyce O'Shaughnessy, Mary Lisha Paul, Bismark Baidoo, Lavanya Sudharshan
Journal: Journal of Clinical Oncology (2020)

e13059 Background: Ribociclib and abemaciclib in combination with endocrine therapy have demonstrated survival benefit in women with HR-positive/HER2-negative mBC. This study assessed early real-world treatment and dosing patterns of ribociclib for mBC in a US community oncology setting. Methods: This was a retrospective, observational, descriptive study of female mBC patients initiating treatment with ribociclib between March 1, 2017 and September 30, 2018 within the US Oncology Network (USON) and followed through December 31, 2018. USON’s iKnowMed (iKM) EHR database was used to identify patients and medical chart data review was conducted to abstract treatment information. Descriptive analyses were performed to assess patient and treatment characteristics. Results: A total of 161 patients were selected for chart review, of which 116 patients who received ribociclib were confirmed as eligible. The mean age of patients at initiation of treatment was 66 (SD 14) years. Among patients with documented menopausal status, 90% were post-menopausal, and 10% were pre-menopausal. Among patients with documented receptor status, 99% were ER+/HER2-. Patients most commonly initiated ribociclib in the first-line setting (1L n = 52, 2L n = 30, 3L n = 9, 4L+ n = 25) and in combination with letrozole (n = 33, 28.4%). Eastern Cooperative Oncology Group (ECOG) performance score at time of ribociclib initiation was 0-1 in 60.4% of patients. Documented metastatic sites were present in bone (35.3%), lung (8.6%), and liver (6%). The most common comorbidities documented within 6 months of treatment initiation were cardiovascular disease (53.4%), diabetes (19%), and depression (18.1%). Overall, 46.6% (n = 54) of patients received prior neoadjuvant or adjuvant chemotherapy and 32.8% patients (n = 38) received prior neoadjuvant or adjuvant endocrine therapy. 95% of patients started at the full dose of 600mg. One-fourth of patients (n = 29) had a dose-hold and 27.6% (n = 32) patients experienced a dose reduction with ribociclib therapy. Conclusions: This study represents early ribociclib uptake in a real-world setting in the US. Early utilization demonstrates patients receiving ribociclib are older and sicker than those in pivotal clinical trials. Substantial heterogeneity in ribociclib initiation by LOT was observed.
云南白药灌肠治疗下消化道出血疗效观察
Authors: 张昌欨, 邓应忠, 沈志祥
Journal: BMJ (2005)

我院自2000年2月至2004年2月对收治的110例下消化道出血患者进行药物灌肠止血治疗,比较观察其疗效,现报道如下. 1.对象和方法:110例患者均因排鲜血便、血块、暗红色血便或黑便来我院就诊.其中黑便者均行胃镜检查,以排除上消化道病变;鲜血便者均行肛诊或肛门镜检查,以排除痔核、肛裂等肛周病变。
High-dose chemotherapy (HDCT) and peripheral-blood stem cell transplant (PBSCT) in patients age 40 or older with relapsed metastatic germ-cell tumors (mGCT).
Authors: Vaibhav Agrawal, Sandra K. Althouse, Rafat Abonour, Mohammad Issam Abu Zaid, Cheryl K Sullivan, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2020)

e17054 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity. Historically, age ≥ 40 years has been associated with greater toxicity and worse outcomes. Methods: 445 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen ( N Engl J Med 2007; 357:340-8). Kaplan-Meier methods and log-rank tests were used for progression free survival (PFS) analysis. Results: 329 pts were age &lt; 40 while 116 pts were age≥40 and HDCT was being used as 2 nd line in 85% and 79%, respectively. Median follow-up time was 42.5 months (range 0.3-173.4). Pulmonary metastasis was more frequent in the age &lt; 40 group (66% vs. 41%, P &lt; 0.001). Patients age≥40 were more likely to have seminoma (45% vs. 14%, P &lt; 0.001), were more likely not platinum refractory (80% vs. 63%, P = 0.0010), and were less likely to complete 2 planned tandem cycles of HDCT (86% vs. 93%, P = 0.03). Grade 3 or higher toxicities were similar between either cohort, except for greater pulmonary toxicity in age≥40 group (8% vs. 2%, P = 0.02). Treatment-related mortality was similar between both age groups: 10 patients (3%) in age &lt; 40 and 4 patients (3.5%) in age≥40 group died from complications of HDCT. 2-year PFS for age &lt; 40 vs. age ≥ 40 was 58.7% vs. 59.6% (P = 0.76) and 2-year OS was 63.9% vs. 61.5% (P = 0.93). When evaluating patients with pure seminoma: 2- year OS for age &lt; 40 vs. 40-50 vs. ≥ 50 was 100% vs 90.3%, vs 81.4%, respectively (P = 0.09). For patients with non-seminoma: 2-year OS was 58.1% vs. 37.1% vs. 54.2%, respectively (P = 0.01). In multivariable analysis for PFS: significant factors predicting worse outcomes included platinum refractory disease (HR = 1.55, P = 0.03), primary mediastinal non-seminoma (HR = 2.41, P = 0.03), not completing 2 cycles of HDCT (HR = 2.47, P = 0.01), and hCG &gt; 1000 at initiation of HDCT (HR = 1.92, P &lt; 0.001). Age was not a significant factor predicting worse outcomes. Conclusions: HDCT plus PBSCT is effective salvage therapy in pts age≥40 with relapsed mGCT. Patients age &gt; 40 experience similar rates of toxicity and treatment-related mortality as those &lt; 40 years of age.
Use of a dynamic disease progression model to estimate prevalence and prognosis for patients with urothelial carcinoma (UC) in the United States (US).
Authors: Sarah Fleming, Kirk Solo, Xuehua Ke, Waleed Shalaby, Arlene O. Siefker-Radtke
Journal: Journal of Clinical Oncology (2020)

e19144 Background: Quantifying the distribution and prognosis of patients with UC as a function of disease stage may allow the impact of existing and novel therapies to be assessed in the real-world setting. We present a dynamic progression model that estimates the incidence, prevalence, and mortality of UC clinical state (CS) in the US. Methods: This UC dynamic progression model used US estimates of UC incidence and distribution of stage at diagnosis from the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) database to establish new patients. Progression and mortality for each CS were based on published clinical trials and OPTUM claims data. The simulation started in 1990, introducing incident patient cohorts allocated across initial CSs (Table). Historical therapy distributions were applied for each year as additional incident UC cohorts were introduced into the model. This proprietary model built to annual point prevalence dynamically through historical incidence, progression and mortality. Results: Based on the progression model, point estimates of prevalence, incidence and annual mortality hazard are provided by stage of disease (Table). For all stages of UC, the model estimated a prevalence of 719,387 patients in 2019. For stage II/III and metastatic UC (mUC) disease, the model estimated that 5,205 and 12,499 patients will die in 2019, respectively. This combines to 17,704 which closely aligns with the SEER estimate of 17,670. Conclusions: This dynamic UC progression model provides estimates for incidence, prevalence, and mortality of UC by clinical state at diagnosis. Incorporating associated claims and clinical data with this model could estimate the benefits of newer therapies as they become available. [Table: see text]
A survey on learning motivation of general practice residents in standardized training in Shanghai's three-year standardized training
Authors: Yu-jie Liu
Journal: BMJ (2010)

A questionnaire survey on learning motivation of standardized training and influence factors was carried out and 94 residents of general practice responded. The results indicated that over 80% respondents showed a positive attitude to study and hoped to obtain opportunity for continuing education;76% thought the training program was basically rational but still need to be improved; 94% felt that the training model should be adapted to the real conditions and work requirements of Chinese community health centers. The authors suggest some measures to improve the training including suitable textbooks, more rational training programs and further improvement of education system.

Key words: 
Standardized training; Learning motivation
Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury
Authors: Wei Chen, Wenjing Zai, Jiajun Fan, Xuyao Zhang, Xian Zeng, Jingyun Luan, Yichen Wang, Yilan Shen, Ziyu Wang, Shixuan Dai, Si Fang, Zhen Zhao, Dianwen Ju
Journal: Theranostics (2020)

Rationale: Interleukin 22 (IL-22) is an epithelial survival cytokine that is at present being explored as therapeutic agents for acute and chronic liver injury. However, its molecular basis of protective activities remains poorly understood. Methods: Here we demonstrate that IL-22 inhibits the deteriorating metabolic states induced by stimuli in hepatocytes. Utilizing cell biological, molecular, and biochemical approaches, we provide evidence that IL-22 promotes oxidative phosphorylation (OXPHOS) and glycolysis and regulates the metabolic reprogramming related transcriptional responses. Results: IL-22 controls metabolic regulators and enzymes activity through the induction of AMP-activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR), thereby ameliorating mitochondrial dysfunction. The upstream effector lncRNA H19 also participates in the controlling of these metabolic processes in hepatocytes. Importantly, amelioration of liver injury by IL-22 through activation of metabolism relevant signaling and regulation of mitochondrial function are further demonstrated in cisplatin-induced liver injury and steatohepatitis. Conclusions: Collectively, our results reveal a novel mechanism underscoring the regulation of metabolic profiles of hepatocytes by IL-22 during liver injury, which might provide useful insights from the bench to the clinic in treating and preventing liver diseases.
Expression profile and potential regulatory pathways of SFTPA1 in human tumors.
Authors: Lu Yuan, Mi Yang, Xixi Wu, Wenqi Huang, Yuting Wu, Jihong Hwang, Jian Guan, Laiyu Liu
Journal: Journal of Clinical Oncology (2020)

e15675 Background: Pulmonary surfactant protein A1(SFTPA1) plays a critical role in maintaining lung tissue homeostasis and its disruption could cause lung diseases and even lung cancer. Despite the finding that SFTPA1 is a potential biomarker for lung cancer, the expression profile and molecular mechanism of SFTPA1 in pan-cancer remain unclear. Methods: The expression of SFTPA1 in BALB/c mice, human normal tissues and human tumor tissues were explored by immunohistochemistry assay. The prognostic values were evaluated by Kaplan-Meier Plotter Database Analysis. Principal components analysis and GO and KEGG pathway enrichment analyses were exerted to identify the functional heterogeneity of SFTPA1 in various tumors. Multiple databases were used to analyze immune infiltrates and regulation networks of SFTPA1. Results: This study described the expression profile of SFTPA1 in various organs and tissues of BALB/c mice and various types of human tumor tissues. Interestingly, we found the expression level of SFTPA1 mRNA was associated with different prognosis in different cancers, even in Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC). The further analysis confirmed a functional heterogeneity of SFTPA1 across diverse cancer types. Significantly, SFTPA1 might regulate tumor microenvironment by affecting the polarization of M2 macrophages in LUAD and LUSC. Furthermore, we found the has-miR-3200-3p-HNF1B-SFTPA1 network was a potential upstream regulatory mechanism of SFTPA1 in LUSC. Conclusions: Our study elaborated expression profile and potential regulatory pathways of SFTPA1 in human solid cancers, and might provide a potential immune infiltration biomarker for lung cancer.
Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study
Authors: Carl C. Crodel, Kathleen Jentsch-Ullrich, Steffen Koschmieder, Dietrich Kämpfe, Martin Griesshammer, Konstanze Döhner, Philipp J. Jost, Denise Wolleschak, Susanne Isfort, Frank Stegelmann, Stefanie Jilg, Verena Hofmann, Guiseppe Auteri, Tobias Rachow, Philipp Ernst, Annamaria Brioli, Marie von Lilienfeld-Toal, Andreas Hochhaus, Francesca Palandri, Florian H. Heidel
Journal: Leukemia (2020)
Controversial risk factors for cholangiocarcinoma.
Authors: Muhammad Talal Sarmini, Firas Baidoun, Anas M Saad, Mohamed Gad, Muhamad Alhaj Moustafa
Journal: Journal of Clinical Oncology (2020)

e16662 Background: Cholangiocarcinoma (CCA) is a relatively rare malignancy accounting for 3% of gastrointestinal cancers in the US. While multiple risk factors for CCA are established and well-studied, other potential risk factors are still controversial and not well established. Herein, we used a large national database to investigate possible risk factors and associations. Methods: We used the National Inpatient Sample (NIS) database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of CCA using the appropriate ICD-9 codes. We used multivariate logistic regression to assess the association between obesity, alcohol abuse, smoking, diabetes mellitus (DM), and non-alcoholic fatty liver disease (NAFLD). Results: We reviewed 30,955,295 admissions of which 20,030 had CCA. CCA Patients were older compared to the rest of the patients (mean age 67 years ±12.8 vs. 57±20.6, P &lt; .001) and had less female patients (48% vs 59%, P &lt; .001). Patients’ characteristics are shown in the table. After adjusting for viral hepatitis B (HBV), viral hepatitis C (HCV), liver cirrhosis, inflammatory bowel disease (IBD), primary sclerosing cholangitis (PSC), and bile duct stones, logistic regression showed DM to be proportionately associated with CCA (OR = 1.04, 95%CI[1.01-1.08], P &lt; .001), whereas alcohol, smoking and obesity were all inversely associated with CCA; OR = 0.75, 95%CI [0.69-0.81], P &lt; .001, OR = 0.75, 95%CI [0.71-0.79], P &lt; .001 and OR = 0.71, 95%CI [0.67-0.75], P &lt; .001, respectively. In addition, compared to whites, Hispanic and Asian/Pacific Islander races were proportionally associated with CCA; OR = 1.27, 95%CI [1.21-1.34], P &lt; .001, and OR = 1.79, 95%CI, [1.67-1.92], P &lt; .001, respectively, while black race was inversely associated with CCA (OR = 0.85, 95%CI [0.81-0.89], P &lt; .001). Conclusions: In our large database study, we found that patients with diagnosis of DM or being from certain minority ethnic groups are associated with increased incidence of CCA. Other factors like alcohol and smoking were associated with decreased incidence of CCA, but those factors may be under reported. This raises the need for further evaluation for these factors and their effect on CCA incidence and outcomes in those specific groups. [Table: see text]
血脂异常的治疗策略与临床常见问题
Authors: 叶平, 盛莉
Journal: BMJ (2007)

冠心病(CHD)是多种危险因素引发的慢性疾病,血脂异常是重要的危险因素之一.近年来随着经济的迅速发展,生活条件的改善,人们的饮食结构的改变和运动量的减少,使人体内能量处于过剩状态,导致糖代谢和脂质代谢的异常。
特殊类型胆囊结石腹腔镜胆囊切除术316例
Authors: 郭吕, 顾建伟, 朱景元, 王春生, 陶卫东, 顾卯林
Journal: BMJ (2005)

胆囊结石合并急性胆囊炎、胰腺炎以及肝硬化或有腹部手术史的患者,一般认为腹腔镜胆囊切除术的并发症高于开腹胆囊切除术.为进一步探讨此类疾病腹腔镜胆囊切除术的适应证及手术技巧,我院自1998年1月至2004年1月共行特殊类型胆囊结石腹腔镜胆囊切除术316例,现报告如下。
ECOG-ACRIN 5162: A phase II study of osimertinib 160 mg in NSCLC with EGFR exon 20 insertions.
Authors: Zofia Piotrowska, Yating Wang, Lecia V. Sequist, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2020)

9513 Background: EGFR exon 20 insertions (ins20), which comprise 4-10% of EGFR-mutant NSCLC, are generally refractory to first- and second-generation EGFR TKIs. While the clinical activity of the third-generation EGFR TKI osimertinib against EGFR ins20 is unknown, preclinical studies suggest its favorable therapeutic window may allow for inhibition of EGFR isn20 at clinically-achievable doses (Hirano, Oncotarget 2015). We report the results of EA5162, a single-arm, phase II study of osimertinib 160 mg in NSCLC pts with EGFR ins20 (NCT03191149). Methods: Pts with advanced NSCLC with an EGFR ins20 mutation identified by any local, CLIA-certified tissue assay were treated with osimertinib 160 mg daily until progression, intolerable toxicity or withdrawal. At least one prior line of therapy was required; stable, asymptomatic brain metastases were allowed. The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival. The estimated sample size was 19 patients. Results: 21 pts were enrolled between 4/2018 and 7/2019 (median age 65; 15 female, 6 male; median 2 prior therapies); 1 patient did not meet eligibility criteria due to laboratory studies obtained 1 day out of window. As of 1/21/20, 6 pts remain on treatment. Among the 20 eligible pts, the best response was PR in 4 pts and CR in one pt, for a confirmed ORR of 25%; 12 (60%) pts had SD. The median PFS was 9.7 months (95% CI, 4.07, NA), median duration of response (DOR) was 5.7 months (95% CI, 4.73, NA.) Grade &gt; 3 treatment-related adverse events (TRAE) observed in &gt; 1 pt included anemia (n=2), fatigue (n=2), prolonged QT interval (n=2.) One pt had grade 4 respiratory failure, there were no grade 5 TRAEs. One pt discontinued study treatment due to grade 3 anemia. Conclusions: Osimertinib 160mg daily is well-tolerated and showed clinical activity in EGFR ins20-mutant NSCLC with a response rate of 25%, disease control rate of 85%, and mPFS of 9.7 months. The adverse events with osimertinib 160 mg QD in this cohort were consistent with other reports of this regimen; grade 3 rash and diarrhea were not observed. Clinical trial information: NCT03191149 .