tbuckley/cabot-search huggingface dataset:
Clinicopathological features and outcomes of patients with esophageal cancer undergoing neoadjuvant chemoradiation (chemoRT) in Southern Brazil: A comparison to the Worldwide Esophageal Cancer Collaboration.
Authors: Gustavo Cartaxo de Lima Gössling, Bruno Siliprandi Pinto, Eduardo Ferreira Martins, Rafaela Kathrine da Silva, Nicolas Peruzzo, Gilberto Schwartsmann, Aparna Raj Parikh
Journal: Journal of Clinical Oncology (2020)

e16535 Background: Despite low- and middle-income countries representing 80% of esophageal cancer global burden, TNM staging is based on data from the Worldwide Esophageal Cancer Collaboration (WECC) that is mainly composed of patients from developed countries. Notably, 87.8% of patients staged after neoadjuvant chemoRT in the WECC were from North America or Europe and only 0.09% (N = 7) from Latin America (LA), raising questions about its applicability. We wanted to see if the characteristics of patients undergoing neoadjuvant chemoradiation in LA were representative of patients in the WECC. Methods: We retrospectively identified patients with esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) who underwent chemoRT at Hospital de Clínicas de Porto Alegre (HCPA), an academic hospital in southern Brazil, and compared their clinicopathological features, treatments and outcomes data with WECC patients. WECC data were extracted from previous publications. Results: Compared to WECC, there were no differences in age (ESCC: 61±7.7 vs. 61±9.4, P = 0.91; EAC: 62±7.2 vs. 61±9.8, P = 0.67) and sex (female: 30.0% vs. 33.2%, P = 0.64; 30.8% vs. 11.6%, P = 0.06). However, we found statistically significant differences in histology (ESCC: 79.4% vs. 26.5%, P &lt; 0.001), PS 0/1/≥2 (ESCC: 24/70/6% vs. 50.6/41.7/7.7%, P = 0.002; EAC: 38.5/61.5/0% vs. 34.9/61.5/3.6%, P = 0.91), active tobacco use (62% vs 27.8%, P &lt; 0.001; 38.5% vs. 15.7%, P &lt; 0.001), weight loss (8.4±5.8Kg vs. 2.6±6Kg, P &lt; 0.001; 14.0±11.6Kg vs. 3,6±7,1Kg, P &lt; 0.001), location (upper/middle/lower: 0/30/70% vs. 16.3/46.6/37.1%, P &lt; 0.001; 0/0/100% vs. 0.7/3/96.3%, P = 0.63) and lymphadenectomy extension ( &gt; 20 resected lymph nodes: 8.6% vs. 38.1%, P &lt; 0.001; 0% vs. 37.9%, P = 0.027). There were no statistically significant differences in pathologic stage (Table) or overall survival in 30 days and 1 year from treatment decision (97.7% vs 98%, P = 0.69; 74.7% vs 75%, P = 0.78). Conclusions: Despite clinically significant differences in presentation were found, they did not implicate worse prognosis in this analysis. [Table: see text]
Correlating immune toxicity, blood cell counts, and overall survival in cancer patients receiving immune therapy.
Authors: Rong Lu, Donglu Xie, Yvonne Gloria-McCutchen, Jessica Saltarski, Mitchell S. von Itzstein, David Hsieh, Mary Katherine Watters, Benjamin Aaron Bleiberg, Vinita Popat, Murtaza Ahmed, Farjana Fattah, David E. Gerber, Shaheen Khan, Jason Park, Edward Wakeland, Saad A. Khan
Journal: Journal of Clinical Oncology (2020)

3043 Background: Baseline circulating white blood cell differential counts have been proposed as possible markers of response to Immune therapy (ICI) and immune toxicity (irAE), but have not been validated for clinical practice. Methods: 214 patients with various cancers receiving ICI had clinical lab results and overall/organ specific irAE analyzed. Absolute lymphocyte (ALC), eosinophil (AEC) and neutrophil (ANC) counts &lt;7 days of starting and 3-12 weeks after ICI were correlated with survival and development of irAE. The association between overall irAE and cell count changes was evaluated using multivariate logistic regression, adjusting for patients’ age, gender, race, and including all 3 types of cell count changes in one model. The association between overall survival and cell counts changes was tested using multivariate Cox proportional hazard model, adjusting for age, gender, race, and overall irAE (yes/no). Results: The combination of MEDIAN rise or fall in ALC, ANC and AEC after ICI combined with development of irAE was associated with altered overall survival (OS). Higher statistically significant (p=&lt;0.05) OS was seen in patients with AEC↑/irAE+(n=94; median OS 14.9 months), ANC↓/irAE+(60; 17.9 mo), ALC↑/irAE+(65; 11.5 mo), ALC↓/irAE+(92; 12.2 mo). Lower OS was seen with ANC↑/irAE-(21; 5.4 mo), ALC↑/irAE-(9; 5.8 mo), ALC↓/irAE-(24; 6.1 mo). All these relationships were unchanged if patients were grouped into ANY rise during the 3-12 weeks rather than median. After multivariable adjustment for age/sex/race there was statistically significant association between higher baseline ALC and development of any irAE (p=0.05) and grade ≥2 irAE (p=0.02). No association was seen between overall toxicities and ANC or AEC. Organ-specific irAE’s with statistically significant associations included pneumonitis:↓AEC (p=0.05), hepatitis:↓ANC (p=0.05), hypothyroidism:↓ANC (p=0.02), colitis:↑ALC (p=0.02). Skin rash, hypophysitis and adrenalitis were not associated with any cell count changes. Conclusions: In patients with cancer receiving immune therapy, the predictive value of serial monitoring in ALC, AEC and ANC is greatly enhanced by the addition of irAE detection. irAEs appear to be a greater predictor of survival than changes in blood counts. In contrast to prior reports we found ANC/ALC/AEC in isolation were less reliable in predicting improved survival. Lack of standardized methods of assessing irAE’s confound identifying strong associations with clinical lab-derived cell counts.
In-hospital outcomes of splanchnic vein thrombosis including Budd Chiari syndrome associated with GI malignancies.
Authors: Shivani Handa, Kamesh Gupta, Ahmad Khan, Kathan Mehta, Anup Kasi
Journal: Journal of Clinical Oncology (2020)

e16503 Background: Patients with gastrointestinal (GI) malignancies are at increased risk of developing splanchnic vein thrombosis (SVT). However, there is a dearth of information about the epidemiology of splanchnic vein thrombosis associated with specific GI malignancies. We sought to compare the differences in hospitalizations and mortality related to SVT among various GI malignancies. Methods: We included the top three discharge diagnoses to identify cases of splanchnic vein thrombosis (portal/mesenteric/hepatic and splenic vein thrombosis) along with a secondary diagnosis of a GI malignancy, namely esophagus, gastric, hepatic, colorectal, pancreatic and cholangiocarcinoma within the 2010-2014 Nationwide Inpatient Sample (NIS). Outcomes including mortality, hospitalization charges and length of stay were compared for different types of GI malignancies for SVT hospitalizations using the chi-square test. Complications related to SVT were also identified. Data was analyzed using STATA 15. Results: There were 320,804 total weighted admissions for SVT, of which 33,556 or 11.6% occurred in patients with GI malignancies. Hepatic cancer was the most common GI malignancy associated with SVT, responsible for 5.1% of all cases, followed by pancreatic cancer (2.76% cases). Hepatic vein thrombosis was the commonest type of SVT occurring in patients with GI malignancy. Hospitalizations for SVT in GI malignancies increased from 5743 in 2010 to 8415 in 2014, representing an increase of 46% over 5 years. On univariate analysis, patients with esophageal cancer and SVT had higher rates of cardiac arrest (3.5% vs 0.7% average for other cancers, p = 0.03), but there were no significant differences in rates of other complications studied including intracranial hemorrhage, requirement for blood transfusion, mechanical ventilation or variceal bleeding. Inpatient mortality rate for admission with SVT was the highest for esophageal cancer (21.1%), followed by gastric cancer (17%) against an average of 9.3% for all GI malignancies (p &lt; 0.05).The median cost of an admission for a patient with SVT were highest for esophageal cancer $102,452, followed by colorectal cancer ($97,491) and the least for hepatic cancer ($67,007). Conclusions: We found that hospitalizations for splanchnic vein thrombosis in patients with GI related malignancies has been steadily increasing and represent a significant burden. Hospitalizations for SVT in esophageal, gastric and colorectal cancer patients bear poorer outcomes as compared to hepatic cancer.
糜烂性胃炎治疗后发作性背部疼痛消失一例
Authors: 李光强, 宋瑞丽, 刘晓霞
Journal: BMJ (2007)

患者男,58岁,因发作性后背部疼痛6年,腹部胀痛加重2个月就诊.6年前因连续疲劳1个月出现后背部疼痛(T5～10之间),伴腹部胀气.背部疼痛呈发作性,每次10～30 min,表现为突发性,无先兆,可以在看书、走路和朋友谈话时发生;发作无规律,与进食无关,但冬春季节发作较频繁。
Is prostate brachytherapy a dying art? Evidence of increasing utilization in Ontario, Canada.
Authors: Mark Thomas Corkum, Gerard Morton, Alexander V. Louie, Glenn Bauman, Lucas Mendez, David D'Souza, Robert Edward Dinniwell, Vikram M. Velker, Andrew Warner, George Rodrigues
Journal: Journal of Clinical Oncology (2020)

e17608 Background: A worldwide decline in prostate brachytherapy (BT) utilization has been reported in multiple health care settings/jurisdictions, despite strong evidence for efficacy and safety compared to other alternatives. We sought to evaluate contemporary trends in BT, EBRT and prostatectomy utilization in a publicly funded healthcare system. Methods: Men with localized prostate cancer diagnosed and treated between 2007 and 2017 in Ontario, Canada were identified using administrative data from the Institute for Clinical Evaluative Sciences. Men were coded to have received EBRT, BT (monotherapy or boost) or prostatectomy as initial definitive management. Trends were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to evaluate patient-, tumour-, and provider-factors on treatment utilization over time. Results: 57,655 men were included in our study. Prostate BT use increased from 7.5% of all treatments in 2007 to 15.4% in 2017 ( p&lt; 0.01), primarily due to increased use of BT boost (1.7% in 2007 to 10.4% in 2017, p &lt; 0.01). Relative to EBRT, BT use increased from 17.9% in 2007 to 28.1% in 2017 ( p&lt; 0.01). On multivariate analysis (MVA), BT boost use increased by 28% per year (OR 1.28, 95% CI 1.26–1.31, p&lt; 0.01) and BT monotherapy use increased by 12% per year (OR 1.12, 95% CI 1.10–1.14, p&lt; 0.01), offset by decreasing prostatectomy use (12% per year, OR 0.88, 95% CI 0.87–0.89, p&lt; 0.01). Comparing BT to EBRT, the strongest predictors of receiving BT were geographic residence (OR 27.6, 95% CI: 20.3–37.6, p&lt; 0.01 between highest/lowest Local Health Integration Networks) and whether the first consulting radiation oncologist performed BT (OR 3.46, 95% CI: 3.15–3.80, p&lt; 0.01). Other significant factors predicting BT use vs. EBRT included lower age, lower PSA, lower Charlson comorbidity score and increasing neighborhood income quintile. Low-intermediate, high-intermediate and high-risk groups were predictive of receiving BT boost, whereas BT monotherapy was predominantly used in low-risk disease. Conclusions: Contrary to trends observed in other jurisdictions, utilization of prostate BT is increasing over time in Ontario. However, substantial variation in BT utilization was found, strongly driven by both geographic region and radiation oncologist BT practice patterns. To our knowledge, this is the first study to report increasing BT utilization in the era of dose-escalated EBRT, with Ontario potentially serving as a model to promote BT utilization elsewhere.
A new CRISPR mediated intestinal tumor mouse model targeting four canonical tumor suppressor genes.
Authors: Hajime Kashima, Daniel Veronese-Paniagua, Anthony Fischer, Blair Madison, Deborah Rubin
Journal: Journal of Clinical Oncology (2020)

e16064 Background: Mouse models of intestinal tumorigenesis have been developed and many of them involve mutations in the Apc gene. However, human intestinal tumors contain multiple additional sporadic mutations in tumor suppressor genes (TSGs). Our goal is to develop a novel mouse model of intestinal tumorigenesis that can recapitulate the natural history of mutations in diverse stages of tumor development. Methods: We used multiple guide RNAs to achieve random mutations in the canonical TSGs, Apc, Pten, Smad4, and Tp53. We generated transgenic (PPAS) mice that constitutively express the appropriate guide RNAs. Moreover, we achieved inducible Cas9 expression in icCas9N mice intestine using the Villin promoter to drive both a doxycycline-dependent activator and a doxycycline-inactivated repressor. We fed the doxycycline chow to PPAS:icCas9 double transgenic mice from the age of 6 to 8 weeks, and harvested intestine at 12 weeks. Results: We examined seven PPAS;icCas9 mice, and detected intestinal tumors in all the mice. Two mice had small intestinal tumor, three mice had colonic tumor, and two mice had tumors in both small and large intestine. The average number of tumors were 0.86, 1.57, 2.43 in small intestine, colon, and both respectively. We analyzed mutations in 11 tumors in 6 mice. The mutation patterns of Apc, Pten, Smad4 and Tp53 in tumors shared three distinct patterns. One was characterized by mutations in all four TSGs (n = 9). The second showed mutation in APC and Smad4 and Pten (n = 1). The third showed mutation only in Tp53 (n = 1). Normal intestine and colon in PPAS:icCas9 mice had no mutations. Conclusions: This model provides a powerful platform for modeling intestinal tumorigenesis driven by the canonical signaling pathway which are commonly dysregulated in colon cancer. This model provides a means for rapid development of intestinal tumors in mice, enabling an investigation of the relationship between novel candidate regulators of tumorigenesis and the canonical signaling pathways regulated by these four common TSGs. [Table: see text]
Deep learning equal to dermatologists in classifying lip disorders
Authors: S.I. Cho, S. Sun, J. Mun, C. Kim, S.Y. Kim, S. Cho, S.W. Youn, H.C. Kim, J.H. Chung
Journal: British Journal of Dermatology (2020)

Lip cancers are relatively rare, but early diagnosis is important for a good outcome. Unfortunately, many patients experience a delay in diagnosis. A new machine learning method, deep convolutional neural networks (DCNNs), uses algorithms which can reportedly be used to classify dermatological diseases at the same standard as board-certified dermatologists. However, this has not been verified for locations such as the lips, scalp, and genitals. A DCNN was used to classify malignant (cancerous) and benign (non-cancerous) lip disorders and its performance was evaluated. The images in this study were taken from the photo database of Seoul National University Hospital (SNUH) in South Korea. To validate the results, additional images were collected from two other affiliated hospitals. A total of 1973 lip images from SNUH were used including 853 malignant and 1120 benign diseases. The DCNN was trained with 1629 images (743 malignant, 886 benign) and its performance was evaluated using testing and external validation sets containing 344 and 281 images, respectively. For comparison, 44 participants with different levels of training were asked to classify the images. The study found that the DCNN's performance was equivalent to the dermatologists, and was superior to the non-dermatologists when classifying malignancy. When they referenced the DCNN result, non-dermatologists performed significantly better. Thus, DCNNs can be used to classify lip diseases at a standard equivalent to a board-certified dermatologist and they can help unskilled physicians to discriminate between benign and malignant lip diseases. DCNNs could therefore be used to improve diagnosis and consequent patient outcomes for those with suspected lip cancers. This is a summary of the study: Dermatologist-level classification of malignant lip diseases using a deep convolutional neural network
Abstract 14396: TRIM2 and CREBRF Are Novel Regulators of Angiogenic Functions in Human Coronary Artery Endothelial Cells
Authors: Nathan K Wong, Emma Solly, Stephen Nicholls, Peter Psaltis, Martin K Ng, Christina A Bursill, Joanne T Tan
Journal: Circulation (2019)

Angiogenesis is critical as an adaptive response to ischemia, yet is pathological in inflammation and tumorigenesis. High-density lipoproteins (HDL) modulate angiogenesis in a context-specific mann...
Correlation between internal thyroid function and intrahepatic cholestasis in pregnancy
Authors: Hong Zhou, Qiu-wei Wang, Fang Cao, Rui-ping Huang, Zi-qiang Zhu, Da-cheng Sun, Bin Yu
Journal: BMJ (2011)

A total of 166 women with intrahepatic cholestasis in pregnancy (ICP) participated in the study. Serum levels of thyroid stimulating hormone (TSH), free thyroxine 4 (FT4) and thyroid peroxidase antibody (TPOAb) were quantified for all of them with electrochemiluminescence (ECL) technique, and compared with those in normal pregnant women. Results showed that serum TSH and TPOAb [22. 9%(38/166)] increased significantly, but no significant change in serum level of FT4 was observed in women with ICP, as compared to those in normal pregnant women. Overall prevalence of thyroid diseases in ICP women was 35.5% (59/166), significantly higher than that in normal population screened for thyroid disease (17. 1%, 143/837) at the same time period. It suggests that thyroid dysfunction may be involved in pathogenesis of ICP.

Key words: 
Cholestasis;  Thyroid disease
Genomic analysis of advanced malignant soft tissue tumors to suggest effect of genome-wide loss-of-heterozygosity of germline mutations/variants on anti-PD-1 immunotherapy response and survival of the patients.
Authors: Katsuhito Takahashi, Yasutomo Miyaji, Hajime Higuchi, Yoshihiro Komohara, Koichi Doi, Hiroko Sano, Shinsuke Aida, Jun Yashima, Hiromasa Yamamoto, Ken Suzawa, Yuko Takahashi, Shinichi Toyooka, Ayumi Saito, Yu Oyama, Hiroyuki Narahara, Junko Yotsumoto, Yasuo Ono, Satoshi Teraoka
Journal: Journal of Clinical Oncology (2020)

11531 Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Although recent genomic characterization of soft tissue sarcoma revealed massive CNA and an excess of polygenic burden of pathological germline variants, their clinical and therapeutic significance remains to be understood. Methods: We recruited 155 patients with malignant soft tissue tumors (135 female and 20 male, mean age 51, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) of confirmed metastasis/recurrence. Whole exome sequencing was performed as reported in 2018ASCO. The MSI status was analyzed by PCR. Tumor immune microenvironment was assessed by immunohistochemistry. Results: Of the 595 COSMIC genes, heterozygous germline mutations/variants of the genome-wide 0-44 genes (av. 9.7/tumor) showed somatic loss-of-heterozygosity (LOH) with allele frequency of more than 70%. Patients with less than 33% LOH (n=53) in the total of somatic and LOH mutations showed improved 5-year survival rate compared with those (n=102) with more LOH (71% vs 52%, p=0.037). LMS (n=100) had higher value of LOH mutations than other tumors (n=55)(av. 55.5 vs 31.2%, p&lt;0.001). Two patients with bone metastasis, one from liver undifferentiated sarcoma (case 1) and the other from uterine LMS (case 2) were identified as MSI-High and resultant higher TMB of 6.48 and 6.60/Mb, respectively than 1.47/Mb in av. Tumors from both cases had de novo mutations of MMR deficiency as EXO I (A153V) and WRN (S1120F) in case 1 and MSH2 (G674D) in case 2. Case 1 with pleural dissemination was treated with 5 cycles of Pembrolizumab (200mg/body, d1 q3weeks) but was progressive disease, while case 2 had no evaluable lesion after surgical removal of bone metastasis. Number of CD8+ T-cell infiltration (TIL), one of the best parameter with response to PD-1 blockade, was much higher in case 2 than in case 1 (av. 907 vs 290/mm 2 ). Case 2 had no LOH mutations while case 1 had 37% LOH with more total mutations in tumor (16.1 vs 85.9/Mb). Higher values of LOH (av. 67 vs 19%) were clearly correlated with decreased density of CD8+TIL in tumor tissues (av. 9.6 vs 429/mm 2 , n=5, p=0.018). Conclusions: Our results, for the first time, suggest that in malignant soft tissue tumors, accumulation of genome-wide LOH of germline mutations/variants, from which self-antigens could be generated, may influence tumor immune microenvironment, and thus influence immunotherapy response and survival of the patients.
Clinical treatment of postmenopausal ovarian tumors
Authors: Jie Gao
Journal: BMJ (2014)

To analyze the clinical characteristics of postmenopausal ovarian tumors and explore the predict indicators and treatment for ovarian benign and malignant tumors. A retrospective analysis was performed for clinical data and pathological results of 125 patients with postmenopausal ovarian tumors from January 2008 to January 2013. The symptoms of malignant patients included abdominal pain (n=30), bloating (n=11) and weight loss (n=5). It had significant difference compared with benign tumors (P<0.05). Ultrasound showed that there was 44 cystic and solid tumors with 22 malignancies and 57 cystic tumors with 5 malignancies. There was significant difference in morbidity of malignant ovarian tumors between them (P<0.05). The incidence of malignant tumor in 5-10 cm group was 56%. There were significant differences compared with the <5 cm group (P<0.05). The specificity of ultrasound plus a combined detection of CA125 for malignant epithelial tumor of ovary was 91% with a sensitivity of 93%. Thirty-one cases of malignant tumor were accurately diagnosed with preoperative ultrasound. Ultrasound plus CA125 could help distinguish the characteristic of tumors.


Key words: 
Postmenopausal; Ovarian Tumor; Diagnosis