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12/8/23

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional

Abstract

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (p = 0.027). Event-free survival was significantly different in favor of HAM-pegA (p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.

PMID: 32079074 [PubMed]

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Management of Polycythemia Vera: A Survey of Canadian Physician Practice Patterns.

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Management of Polycythemia Vera: A Survey of Canadian Physician Practice Patterns.

Clin Lymphoma Myeloma Leuk. 2019 01;19(1):e37-e42

Authors: Habib LA, Kuo KHM, Panzarella T, Gupta V, Trinkaus M

BACKGROUND: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows

Abstract

BACKGROUND: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 WHO diagnostic criteria of PV are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm Group.

MATERIALS AND METHODS: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society using an online survey-distributing website. Univariate and multivariate analysis was performed.

RESULTS: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all patients with PV (P = .0009). Respondents who were aware of the Canadian Myeloproliferative Neoplasm Group guidelines were more likely to phlebotomize patients to a target hematocrit of < 45% irrespective of gender (P = .042). Younger practitioners were more likely to use age over 60 years as an indication for initiating cytoreductive therapy (P = .0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism.

CONCLUSION: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria.

PMID: 30322792 [PubMed - indexed for MEDLINE]

20:14

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Angiotensin-(1-7) reduces doxorubicin-induced cardiac dysfunction in male and female Sprague-Dawley rats through antioxidant mechanisms.

Am J Physiol Heart Circ Physiol. 2020 Feb 21;:

Authors: Rahimi O, Kirby J, Varagic J, Westwood BM, Tallant EA, Gallagher PE

BACKGROUND: Finding an abdominal mass or hematuria is the initial step in diagnosing Wilms tumor. As the first manifestation of Wilms tumor

Abstract

BACKGROUND: Finding an abdominal mass or hematuria is the initial step in diagnosing Wilms tumor. As the first manifestation of Wilms tumor, it is exceedingly rare for pulmonary tumor embolism to present with cardiac arrest. A case of a patient whose sudden cardiac arrest due to massive pulmonary tumor embolism of Wilms tumor was not responsive to resuscitation is presented.

CASE PRESENTATION: The patient was a five-year-old girl who collapsed suddenly during activity in nursery school and went into cardiac arrest in the ambulance. Unfortunately, she was not responsive to conventional resuscitation. A judicial autopsy conducted at the local police department showed the main cause of her sudden cardiac arrest was attributed to multiple pulmonary tumor embolisms of stage IV Wilms tumor.

CONCLUSIONS: Except for one reported case, treatments were not successful in all eight cardiac arrest cases with pulmonary tumor embolism of Wilms tumor. These results indicate that it is challenging not only to make an accurate diagnosis, but also to provide proper specific treatment in the cardiac arrest setting. We propose that flexible triage and prompt transfer to a tertiary hospital are necessary as an oncologic emergency to get such patients to bridging therapy combined with extracorporeal membrane oxygenation or immediate surgical intervention under cardiopulmonary bypass.

PMID: 30704433 [PubMed - indexed for MEDLINE]

22 February 2020

18:48

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia.

J Clin Med. 2020 Feb 16;9(2):

Authors: Patzke CL, Duffy AP, Duong VH, El Chaer F, Trovato JA, Baer MR, Bentzen SM, Emadi A

INTRODUCTION: Pulmonary artery intimal sarcoma (PAIS) is a rare and highly aggressive tumor, and approximately 80% of pulmonary cases occur i

Abstract

INTRODUCTION: Pulmonary artery intimal sarcoma (PAIS) is a rare and highly aggressive tumor, and approximately 80% of pulmonary cases occur in the pulmonary trunk. We report herein a case of retrograde extension of the sarcoma to the pulmonary valve and right ventricle, which is an uncommon manifestation of this lethal tumor.

PATIENT CONCERNS: A 41-year-old woman was initially diagnosed with pulmonary thromboembolism (PTE) and transferred to our hospital.

DIAGNOSIS: Computed tomographic pulmonary angiography (CTPA) showed that there are low-density filling defects in both pulmonary arteries, and the patient was diagnosed with PTE. However, the ultrasonographers considered that the lesion is a space-occupying type that involves the right ventricular outflow tract and pulmonary valve instead of PTE. Postoperative pathology confirmed the diagnosis of PAIS.

INTERVENTIONS: The patient underwent resection of pulmonary artery sarcoma and endarterectomy.

OUTCOMES: During the follow-up via telephone 1 month after discharge, the patient reported to have been feeling well.

CONCLUSION: Owing to the rarity of the disease and its non-specific clinical manifestations, approximately half of the PAIS cases are misdiagnosed or have a delayed diagnosis. Thus, improving our understanding of the disease and facilitating its early diagnosis are essential.

PMID: 32011489 [PubMed - indexed for MEDLINE]

22:24

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Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.

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Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.

Blood. 2019 11 07;134(19):1645-1657

Authors: Lindström S, Wang L, Smith EN, Gordon W, van Hylckama Vlieg A, de Andrade M, Brody JA, Pattee JW, Haessler J, Brumpton BM, Chasman DI, Suchon P, Chen MH, Turman C, Germain M, Wiggins KL, MacDonald J, Braekkan SK, Armasu SM, Pankratz N, Jackson RD, Nielsen JB, Giulianini F, Puurunen MK, Ibrahim M, Heckbert SR, Damrauer SM, Natarajan P, Klarin D, Million Veteran Program, de Vries PS, Sabater-Lleal M, Huffman JE, CHARGE Hemostasis Working Group, Bammler TK, Frazer KA, McCauley BM, Taylor K, Pankow JS, Reiner AP, Gabrielsen ME, Deleuze JF, O'Donnell CJ, Kim J, McKnight B, Kraft P, Hansen JB, Rosendaal FR, Heit JA, Psaty BM, Tang W, Kooperberg C, Hveem K, Ridker PM, Morange PE, Johnson AD, Kabrhel C, Trégouët DA, Smith NL

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE

Abstract

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. We meta-analyzed GWAS data from 18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE. We generated variant prediction scores of gene expression from whole blood and liver tissue and assessed them for association with VTE. Mendelian randomization analyses were conducted for traits genetically associated with novel VTE loci. We identified 34 independent genetic signals for VTE risk from GWAS meta-analysis, of which 14 are newly reported associations. This included 11 newly associated genetic loci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) of which 6 replicated, and 3 new independent signals in 3 known genes. Further, TWAS identified 5 additional genetic loci with imputed gene expression levels differing between cases and controls in whole blood (SH2B3, SPSB1, RP11-747H7.3, RP4-737E23.2) and in liver (ERAP1). At some GWAS loci, we found suggestive evidence that the VTE association signal for novel and previously known regions colocalized with expression quantitative trait locus signals. Mendelian randomization analyses suggested that blood traits may contribute to the underlying risk of VTE. To conclude, we identified 16 novel susceptibility loci for VTE; for some loci, the association signals are likely mediated through gene expression of nearby genes.

PMID: 31420334 [PubMed - indexed for MEDLINE]

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Lessons from a patient with cardiac arrest due to massive pulmonary embolism as the initial presentation of Wilms tumor: a case report and literature review.

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Lessons from a patient with cardiac arrest due to massive pulmonary embolism as the initial presentation of Wilms tumor: a case report and literature review.

BMC Pediatr. 2019 01 31;19(1):39

Authors: Fukuda A, Isoda T, Sakamoto N, Nakajima K, Ohta T

Objective: To investigate short-term efficacy of laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric

Abstract

Objective: To investigate short-term efficacy of laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision for advanced proximal gastric cancer based on mesangial anatomy. Methods: A case series study was carried out. Case inclusion criteria: (1) patient was confirmed as gastric adenocarcinoma by gastroscopic biopsy before operation; (2) locally advanced gastric cancer was confirmed by abdominal CT before operation; (3) no distant metastases such as liver, lung, and posterior peritoneal lymph nodes, and no tumor directly invading the pancreas, spleen, liver, and colon were verified by superficial lymph node ultrasound, chest and abdominal CT before operation;(4) total gastrectomy or proximal gastrectomy plus D2 lymphadenectomy were performed, and R0 resection was confirmed by postoperative pathology. Exclusion criteria: (1) intraperitoneal dissemination or distant metastasis was found during laparoscopic exploration; (2) No.10 lymph nodes were significantly enlarged or fused into clusters; (3) pathological diagnostic data were incomplete. According to above criteria, the clinicopathological data of 36 patients who underwent laparoscopic spleen-preserving No.10 lymphadenectomy and left epigastrium mesogastric excision based on interspace anatomy for advanced proximal gastric cancer in The First Affiliated Hospital of Zhengzhou University from June 2017 to March 2018 were retrospectively collected and analyzed. The intraoperative conditions, postoperative recovery and complications of patients were analyzed. Results: In 36 patients, the mean age was (59.8±8.0) years, the mean BMI was (23.9±3.5) kg/m(2), and 8 cases (22.2%) received preoperative chemotherapy. All the patients underwent successfully the laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision. In the examination of postoperative resected specimens, it was found that the mesangial boundary of the upper and posterior part of the stomach was smooth, indicating the efficiency of complete mesangial resection. No case was converted to open operation. The mean time of lymph node dissection and mesangial resection was (34.2±11.4) minutes. The mean blood loss during operation was (44.8±21.3) ml. The mean number of lymph node dissection per patient was 45.6±17.6. The mean number of No. 11p+11d lymph node dissection was 3.1± 2.8 per patient, and 7 patients were pathologically positive with metastasis rate of 19.4% (7/36). The mean number of No.10 lymph node dissection was 2.9±2.5 per patient, and 2 patients were pathologically positive with metastasis rate of 5.6% (2/36). The time to postoperative flatus was (3.8±0.6) days, time to removal of nasogastric was (1.9±0.7) days, time to the first intake of fluid was (3.0±0.4) days, time to removal of drainage tube was (6.0±1.2) days. Postoperative mean hospital stay was (12.8±4.0) days. One case (2.7%) developed pulmonary embolism and 1 case (2.7%) developed gastroplegia after operation. The morbidity of postoperative complication was 5.6% (2/36). No operative site infection, postoperative bleeding and death within postoperative 30-day were observed. All the 36 patients were followed up and the median follow-up was 18 months (12-28 months). Seven patients died of tum[...]

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or relapse and metastasis (3 cases died within postoperative 1 year) and another 1 case developed colonic cancer 17 months after operation. Conclusion: Laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision for advanced proximal gastric cancer based on mesangial anatomy is safe and feasible.

PMID: 32074799 [PubMed - in process]

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Pulmonary intimal sarcoma involving the pulmonary valve and right ventricular outflow tract: A case report and literature review.

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Pulmonary intimal sarcoma involving the pulmonary valve and right ventricular outflow tract: A case report and literature review.

Medicine (Baltimore). 2020 Jan;99(3):e18813

Authors: Xu R, Zhao Y, Xu X, Liu S, Hu C, Lv D, Wu H

Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure

Abstract

Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.

PMID: 32075047 [PubMed - in process]

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Vaginal estrogen use for genitourinary symptoms in women with a history of uterine, cervical, or ovarian carcinoma.

Int J Gynecol Cancer. 2020 Feb 18;:

Authors: Chambers LM, Herrmann A, Michener CM, Ferrando CA, Ricci S

OBJECTIVE: Menopausal symptoms may adversely affect quality of life and health in women diagnosed with a gynecologic malignancy

Abstract

OBJECTIVE: Menopausal symptoms may adversely affect quality of life and health in women diagnosed with a gynecologic malignancy. The aim of this study was to determine the incidence of adverse outcomes, including cancer recurrence, venous thromboembolism, and secondary malignancies, among patients with a history of endometrial, ovarian, or cervical cancer prescribed vaginal estrogen for genitourinary syndrome of menopause.

METHODS: A retrospective cohort study was performed including women who were diagnosed with endometrial, ovarian, or cervical cancer from January 1, 1991 to December 31, 2017 and subsequently treated with vaginal estrogen for genitourinary syndrome of menopause. Patients were included if not undergoing active cancer treatment and were disease-free based on most recent cancer surveillance visit with physical exam and/or imaging. Demographics, oncologic variables, estrogen use, and adverse outcomes were recorded. Descriptive statistics and univariate analysis were performed.

RESULTS: Of 244 women who received vaginal estrogen, 52% (n=127) had a history of endometrial, 25.4% (n=62) cervical, 18.9% (n=46) ovarian cancer, and 3.7% (n=9) low malignant potential tumors. The mean age and body mass index were 55.5±12.5 years and 29.2±8.6 mg/kg2, respectively. With a median follow-up of 80.2 months, the incidence of recurrence for endometrial, ovarian, and cervical cancer was 7.1% (n=9), 18.2% (n=10), and 9.7% (n=6), respectively. In patients with endometrial cancer who recurred, the incidence was 2.4% (n=3) for stage I/II and 4.7% (n=6) for stage III/IV disease. Similarly, recurrence rates for ovarian cancer were 4.3% (n=2) for stage I/II and 17.4% (n=8) for stage III/IV disease. All cervical cancer recurrences were in patients with stage I/II disease. Adverse outcomes including breast cancer (1.6%, n=4), secondary malignancy (2.5%, n=6), and venous thromboembolism (2.5%, n=6) were rare.

CONCLUSION: In women with a history of endometrial, ovarian, or cervical cancer prescribed vaginal estrogen use for genitourinary syndrome of menopause, adverse outcomes, including recurrence and thromboembolic events, are infrequent. Vaginal estrogen may be considered safe in gynecologic cancer survivors.

PMID: 32075898 [PubMed - as supplied by publisher]

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[Short-term efficacy evaluation of laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision for advanced proximal gastric cancer based on mesangial anatomy].

Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Feb 25;23(2):177-182

Authors: Zhang YF, Chen P, Sun JG, Fan XJ, Wang YM, Gao YS

Recent clinical investigations indicate that anthracycline-based chemotherapies induce early declines in heart mass in cancer patients.

Abstract

Recent clinical investigations indicate that anthracycline-based chemotherapies induce early declines in heart mass in cancer patients. Heart mass decline may be caused by a decrease in cardiac cell number due to increased cell death, or by a reduction in cell size due to atrophy. We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). However, the signaling pathway downstream of CDK2 remains to be characterized, and it is also unclear whether the same pathway mediates cardiac atrophy. Here, we demonstrate that DOX exposure induces CDK2-dependent phosphorylation of the transcription factor forkhead box O1 (FOXO1) at Ser-249, leading to transcription of its pro-apoptotic target gene, Bcl-2-interacting mediator of cell death (Bim). In cultured cardiomyocytes, treatment with the FOXO1 inhibitor AS1842856 or transfection with FOXO1-specific siRNAs protected against DOX-induced apoptosis and mitochondrial damage. Oral administration of AS1842856 in mice abrogated apoptosis and prevented DOX-induced cardiac dysfunction. Intriguingly, the pharmacological FOXO1 inhibition also attenuated DOX-induced cardiac atrophy, likely due to repression of muscle RING finger 1 (MuRF1), a pro-atrophic FOXO1 target gene. In conclusion, DOX exposure induces CDK2-dependent FOXO1 activation, resulting in cardiomyocyte apoptosis and atrophy. Our results identify FOXO1 as a promising drug target for managing DOX-induced cardiotoxicity. We propose that FOXO1 inhibitors may have potential as cardioprotective therapeutics during cancer chemotherapy.

PMID: 32075913 [PubMed - as supplied by publisher]

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Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin.

Molecules. 2020 Feb 14;25(4):

Authors: Zhang Q, Li J, Peng S, Zhang Y, Qiao Y