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Blood Cancer Journal Jun 2024The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been...
The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been investigated in several studies. However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done. Here, we performed error-corrected-NGS-MRD in 189 patients homogeneously treated in the ALFA-0702 study (NCT00932412). Persistence of non-DTA mutations (HR = 2.23 for RFS and 2.26 for OS), and DTA mutations (HR = 2.16 for OS) were associated with poorer prognosis in multivariate analysis. Persistence of at least two mutations in complete remission (CR) was associated with a higher cumulative incidence of relapse (CIR) (HR = 3.71, p < 0.0001), lower RFS (HR = 3.36, p < 0.0001) and OS (HR = 3.81, p = 0.00023) whereas persistence of only one mutation was not. In 100 analyzable patients, WT1-MRD, but not NGS-MRD, was an independent factor for RFS and OS. In the subset of 67 NPM1 mutated patients, both NPM1 mutation detection (p = 0.0059) and NGS-MRD (p = 0.035) status were associated with CIR. We conclude that detectable NGS-MRD including DTA mutations correlates with unfavorable prognosis in AML. Its integration with alternative MRD strategies in AML management warrants further investigations.
Topics: Humans; Neoplasm, Residual; Leukemia, Myeloid, Acute; Female; Male; Middle Aged; Nucleophosmin; Adult; Aged; Mutation; High-Throughput Nucleotide Sequencing; Young Adult; Prognosis; DNA Methyltransferase 3A; Aged, 80 and over; DNA (Cytosine-5-)-Methyltransferases; Adolescent; Repressor Proteins; DNA Mutational Analysis
PubMed: 38871702
DOI: 10.1038/s41408-024-01078-8 -
BMC Endocrine Disorders Jun 2024Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of...
BACKGROUND
Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky.
CASE PRESENTATION
A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery.
CONCLUSION
Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.
Topics: Humans; Female; Aged; Lymphatic Metastasis; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Carcinoma, Anaplastic; Prognosis; Fatal Outcome; Neck; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 38867258
DOI: 10.1186/s12902-024-01617-1 -
Surgical Case Reports Jun 2024Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal...
BACKGROUND
Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants.
CASE PRESENTATION
The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively.
CONCLUSIONS
If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.
PubMed: 38867137
DOI: 10.1186/s40792-024-01936-4 -
Nature Communications Jun 2024Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT...
Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT's adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.
Topics: Humans; Leukemia, Myeloid, Acute; INDEL Mutation; CRISPR-Cas Systems; Nucleophosmin; Neoplasm, Residual; Nuclear Proteins; Proto-Oncogene Proteins B-raf; Genetic Testing; ErbB Receptors; Bacterial Proteins; Endodeoxyribonucleases; CRISPR-Associated Proteins
PubMed: 38866774
DOI: 10.1038/s41467-024-49414-7 -
International Journal of Surgery Case... Jul 2024Cystic lesions in long bones are the radiological presentation of various bone pathologies, they can easily be misdiagnosed and thus mistreated; treatment varies from...
INTRODUCTION
Cystic lesions in long bones are the radiological presentation of various bone pathologies, they can easily be misdiagnosed and thus mistreated; treatment varies from observation to aggressive surgical interventions based on the nature and characteristics of the lesion.
CASE PRESENTATION
A 25-year-old male had a twisting injury to his ankle and his radiographs showed a cystic lesion in the distal tibia that was asymptomatic until he injured his ankle. he had persistent pain since then. and after conservative methods failure, a two-stage surgical intervention was done; first, we curetted the lesion and filled it with antibiotics cement; then the cement was removed with autologous bone grafting. The patient eventually healed and returned to his normal activity level.
DISCUSSION
Brodie's abscess has a similar radiological appearance to other bone neoplasms and tumor-like lesions. Clinically, it is minimally symptomatic, and often initially misdiagnosed; surgical treatment is very effective, but it depends on the size, location, and aggressiveness of the lesion; the goal is to eliminate the infection, refill the residual gap, and restore the normal function, especially in weight-bearing bones.
CONCLUSION
Brodie's abscess is a hideous lesion that is hard to diagnose. It could mimic other tumor-like lesions. However, applying bone cement and a second stage of bone grafting might help maximize the treatment efficiency.
PubMed: 38865946
DOI: 10.1016/j.ijscr.2024.109865 -
Supportive Care in Cancer : Official... Jun 2024We conducted a systematic review to describe health-related quality of life (HRQOL) in rural cancer survivors (RCS), and compare HRQOL between RCS and urban cancer... (Comparative Study)
Comparative Study Review
PURPOSE
We conducted a systematic review to describe health-related quality of life (HRQOL) in rural cancer survivors (RCS), and compare HRQOL between RCS and urban cancer survivors (UCS).
METHOD
We searched Medline, Embase, CINAHL Plus, and PsycINFO for studies with HRQOL in adult cancer survivors living in rural, regional, remote, and urban areas, who had completed definitive primary cancer treatment, without evidence of residual disease. Where available, we used normative and clinically important values to ascribe meaning to HRQOL data.
FINDINGS
Fifteen studies (16 papers) were included. Most were from the US (n = 8) and reported on breast cancer survivors (n = 9). Six HRQOL instruments, collecting data across 16 domains, were used. Three instruments were specific to the survivorship phase. Normative and clinical data were available for 12 studies. Compared with normative populations, RCS had clinically worse physical HRQOL (6/12 studies), better social/family (5/7), and functional (3/6) HRQOL, and there were no differences in emotional or/mental HRQOL (9/12). In six studies with rural-urban comparator groups and normative and clinically important data, RCS and UCS had clinically worse physical (3/6 and 2/6, respectively) and better social/family (3/4 and 2/4 studies, respectively) HRQOL than normative populations. Functional HRQOL was better in RCS (2/4 studies) than UCS and normative populations. In 3/6 studies, there were no clinical differences in emotional or/mental HRQOL between RCS, UCS, and normative populations.
CONCLUSION
Overall, HRQOL is not clearly better or worse in RCS than UCS. Future research should include different tumor types, rural residents, and survivorship-specific HRQOL instruments.
Topics: Humans; Quality of Life; Cancer Survivors; Rural Population; Urban Population; Neoplasms
PubMed: 38864894
DOI: 10.1007/s00520-024-08618-9 -
Scientific Reports Jun 2024In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of...
In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10. We propose this method as an effective MRD assay.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual; Immunophenotyping; Immunoglobulin kappa-Chains; Flow Cytometry; Immunoglobulin lambda-Chains; Female; Male; Immunoglobulin Light Chains
PubMed: 38862612
DOI: 10.1038/s41598-024-64398-6 -
International Journal of General... 2024Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study...
PURPOSE
Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.
PATIENTS AND METHODS
We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.
RESULTS
After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.
CONCLUSION
HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.
PubMed: 38859910
DOI: 10.2147/IJGM.S462844 -
Orthopaedic Surgery Jun 2024It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and... (Review)
Review
OBJECTIVE
It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure.
METHODS
We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed.
RESULTS
All six patients were followed up for 24 to 46 months (mean follow-up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection-related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation.
CONCLUSION
Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long-term disease-free survival with acceptable complications and satisfying neurological function.
PubMed: 38859700
DOI: 10.1111/os.14104 -
Breast Cancer Research : BCR Jun 2024Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune...
BACKGROUND
Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied.
METHODS
Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal-Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC.
RESULTS
There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (T) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response.
CONCLUSIONS
Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + T cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer.
TRIAL REGISTRATION
NCT02022202 . Registered 20 December 2013.
Topics: Humans; Female; Neoadjuvant Therapy; Immunophenotyping; Middle Aged; Breast Neoplasms; Adult; Aged; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Leukocytes, Mononuclear; Biomarkers, Tumor; Prognosis; Lymphocytes, Tumor-Infiltrating; Triple Negative Breast Neoplasms; Prospective Studies; Treatment Outcome; Chemotherapy, Adjuvant
PubMed: 38858721
DOI: 10.1186/s13058-024-01848-z