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Frontiers in Endocrinology 2024Previous observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated...
BACKGROUND
Previous observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated the causal relationship between cathepsins and cancer using Mendelian randomization (MR) analysis.
METHODS
We used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis.
RESULTS
After correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027-1.114, = 0.001, = 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919-0.975, = 0.0002, P = 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001-1.025, = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001-1.034, = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012-1.101, = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949-0.991, = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902-0.944, = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938-0.990, = 0.006).
CONCLUSION
Our MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer.
Topics: Humans; Mendelian Randomization Analysis; Cathepsins; Neoplasms; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Female; Risk Factors
PubMed: 38883596
DOI: 10.3389/fendo.2024.1428433 -
Cureus May 2024Pharyngocutaneous fistula (PCF) is an abnormal connection between the pharynx and skin that can occur after laryngectomy surgery. It can have a significant negative...
Pharyngocutaneous fistula (PCF) is an abnormal connection between the pharynx and skin that can occur after laryngectomy surgery. It can have a significant negative impact on patient recovery, delaying wound healing, requiring prolonged nil-per-oral (NPO) status, and reducing quality of life. Traditionally, the management of PCF has relied on conservative measures or surgical intervention. However, negative pressure wound therapy (NPWT) offers a promising alternative approach. This case study involves three patients who underwent laryngectomy and developed postoperative PCF. All patients received NPWT with a modified suction catheter and low negative pressure (20-40 mmHg). With NPWT, all patients achieved complete wound closure, with healing times ranging from two weeks to six weeks. This suggests that NPWT may significantly accelerate PCF healing compared to traditional methods. However, maintaining an airtight dressing on the neck region can be challenging. This study highlights the potential of NPWT for faster PCF closure after laryngectomy. Further research is needed to optimize NPWT application techniques, explore the impact on long-term outcomes, and establish guidelines for broader clinical use.
PubMed: 38883062
DOI: 10.7759/cureus.60457 -
Journal of Medical Case Reports Jun 2024This paper reports the first case of basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma. (Review)
Review
BACKGROUND
This paper reports the first case of basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma.
CASE PRESENTATION
A 66-year-old Sinhalese male with unilateral hearing impairment and 7th-12th (excluding 11th) cranial nerve palsies was diagnosed radiologically with a head and neck paraganglioma by magnetic resonance imaging of the brain, which revealed a hypointense and hyperintense punctate mass centered at the jugular fossa with intracranial extension. The ascending pharyngeal artery, recognized as the major feeder, was embolized by percutaneous embolization following digital subtraction angiography. Gross total resection of the tumor was followed by an uneventful postoperative recovery. Combined immunohistochemistry and histopathological morphology revealed a basaloid squamous cell carcinoma, following which the patient completed radiotherapy and is at 3-month follow-up currently.
CONCLUSION
This case report discusses the diagnostic pitfalls and management challenges of this rare entity on the basis of prior evidence, as well as a literature review and clinical and surgical analysis.
Topics: Humans; Male; Aged; Head and Neck Neoplasms; Paraganglioma; Diagnosis, Differential; Magnetic Resonance Imaging; Carcinoma, Squamous Cell; Embolization, Therapeutic; Angiography, Digital Subtraction
PubMed: 38858796
DOI: 10.1186/s13256-024-04601-4 -
BMC Cancer May 2024This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with...
Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.
BACKGROUND
This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC).
METHODS
Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses.
RESULTS
Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (D) and V of parotid glands; D and V of submandibular glands; and D of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The D of the parotid and sublingual glands was a risk factor for xerostomia. The D of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia.
CONCLUSIONS
Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.
Topics: Humans; Deglutition Disorders; Male; Xerostomia; Female; Nasopharyngeal Carcinoma; Middle Aged; Radiotherapy, Intensity-Modulated; Retrospective Studies; Follow-Up Studies; Nasopharyngeal Neoplasms; Adult; Aged; Radiation Injuries; Deglutition; Salivary Glands; Radiotherapy Dosage; Prognosis; Young Adult
PubMed: 38802747
DOI: 10.1186/s12885-024-12391-7 -
PeerJ 2024To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal... (Meta-Analysis)
Meta-Analysis
Systematic evaluation and meta-analysis of the prognosis of down-staging human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma using cetuximab combined with radiotherapy instead of cisplatin combined with radiotherapy.
OBJECTIVE
To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV OPSCC).
DESIGN
Meta-analysis and systematic evaluation.
DATA SOURCES
The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE).
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.
RESULTS
A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], = 0.0004; HR = 1.79, 95% CI [1.40-2.29], < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], < 0.0001; HR = 1.66, 95% CI [1.07-2.58], = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], = 0.28).
CONCLUSIONS
Cisplatin + radiotherapy remains the standard treatment for HPV OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies.
PROSPERO REGISTRATION NUMBER
CRD42023445619.
Topics: Humans; Cetuximab; Oropharyngeal Neoplasms; Cisplatin; Chemoradiotherapy; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck; Neoplasm Staging; Papillomaviridae; Antineoplastic Agents, Immunological; Progression-Free Survival; Human Papillomavirus Viruses
PubMed: 38784388
DOI: 10.7717/peerj.17391 -
BMC Genomics May 2024The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific...
BACKGROUND
The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx.
RESULTS
Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed.
CONCLUSIONS
Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.
Topics: Humans; Hypopharyngeal Neoplasms; Single-Cell Analysis; Tumor Microenvironment; Transcriptome; Hypopharynx; Gene Expression Profiling; Male; Sequence Analysis, RNA
PubMed: 38760729
DOI: 10.1186/s12864-024-10321-2 -
Clinical Endoscopy May 2024The literature pertaining to surveillance following treatment for esophageal squamous cell carcinoma (SCC) was reviewed and summarized, encompassing the current status... (Review)
Review
The literature pertaining to surveillance following treatment for esophageal squamous cell carcinoma (SCC) was reviewed and summarized, encompassing the current status and future perspectives. Analysis of the standardized mortality and incidence ratios for these cancers indicates an elevated risk of cancer in the oral cavity, pharynx, larynx, and lungs among patients with esophageal SCC compared to the general population. To enhance the efficacy of surveillance for these metachronous cancers, risk stratification is needed. Various factors, including multiple Lugol-voiding lesions, multiple foci of dilated vascular areas, young age, and high mean corpuscular volume, have been identified as predictors of metachronous SCCs. Current practice involves stratifying the risk of metachronous esophageal and head/neck SCCs based on the presence of multiple Lugol-voiding lesions. Endoscopic surveillance, scheduled 6-12 months post-endoscopic resection, has demonstrated effectiveness, with over 90% of metachronous esophageal SCCs treatable through minimally invasive modalities. Narrow-band imaging emerges as the preferred surveillance method for esophageal and head/neck SCC based on comparative studies of various imaging techniques. Innovative approaches, such as artificial intelligence-assisted detection systems and radiofrequency ablation of high-risk background mucosa, may improve outcomes in patients following endoscopic resection.
PubMed: 38725400
DOI: 10.5946/ce.2023.263 -
Cureus Apr 2024During the COVID-19 pandemic, excess deaths including cancer have become a concern in Japan, which has a rapidly aging population. Thus, this study aimed to evaluate...
During the COVID-19 pandemic, excess deaths including cancer have become a concern in Japan, which has a rapidly aging population. Thus, this study aimed to evaluate how age-adjusted mortality rates (AMRs) for different types of cancer in Japan changed during the COVID-19 pandemic (2020-2022). Official statistics from Japan were used to compare observed annual and monthly AMRs with predicted rates based on pre-pandemic (2010-2019) figures using logistic regression analysis. No significant excess mortality was observed during the first year of the pandemic (2020). However, some excess cancer mortalities were observed in 2021 after mass vaccination with the first and second vaccine doses, and significant excess mortalities were observed for all cancers and some specific types of cancer (including ovarian cancer, leukemia, prostate cancer, lip/oral/pharyngeal cancer, pancreatic cancer, and breast cancer) after mass vaccination with the third dose in 2022. AMRs for the four cancers with the most deaths (lung, colorectal, stomach, and liver) showed a decreasing trend until the first year of the pandemic in 2020, but the rate of decrease slowed in 2021 and 2022. This study discusses possible explanations for these increases in age-adjusted cancer mortality rates.
PubMed: 38721172
DOI: 10.7759/cureus.57860 -
Laryngo- Rhino- Otologie May 2024Squamous cell carcinomas are the most common malignancies in the oral cavity, pharynx, and larynx. Even in the age of the most modern drug treatment methods, radical... (Review)
Review
Squamous cell carcinomas are the most common malignancies in the oral cavity, pharynx, and larynx. Even in the age of the most modern drug treatment methods, radical resection of these tumors is and currently remains the therapeutic gold standard. The loss of anatomical structures associated with surgery inevitably increases the functional deficits caused by the tumor itself. In this context, the extent of functional deficits is largely determined by the extent of resection. Complete organ resections, such as glossectomy, complete palate resection, laryngectomy, or transverse pharyngo-laryngectomy, lead to severe functional deficits, such as swallowing disturbances with life-threatening aspiration and articulation disorders up to the inability to speak. With the help of plastic reconstructive surgery, the lost tissue can be replaced and the specific functions of the upper aerodigestive tract can be preserved or restored.In recent decades, reconstructive surgical procedures have developed enormously in the treatment of malignant tumors of the head and neck. In order to make optimal use of them, a comprehensive, interdisciplinary therapy concept is a prerequisite for positive oncological and functional outcome. In addition to general medical and social parameters, surgical parameters play a crucial role in the choice of the reconstruction method. The extent to which the surgical measures must be interdisciplinary depends on the localization of the defects in the head and neck region and on the type of replacement tissue required. Here, the expertise of plastic surgery, oral and maxillofacial surgery, and abdominal surgery comes into play in particular. The use of different tissues, the combination of different grafts and flaps, or the preforming of donor regions allow reconstructions far beyond the level of simply restoring surface integrity. The functional results and thus the quality of life of patients after surgical therapy of extensive tumors of the mentioned localizations depend decisively on the type of reconstruction. Therefore, in the following review, special emphasis 1 be placed on the choice of reconstruction method and reconstruction technique for tissue loss after resections of HNSCC.
Topics: Humans; Plastic Surgery Procedures; Carcinoma, Squamous Cell; Interdisciplinary Communication; Head and Neck Neoplasms; Patient Care Team; Squamous Cell Carcinoma of Head and Neck; Intersectoral Collaboration
PubMed: 38697141
DOI: 10.1055/a-2181-9088 -
Radiation Oncology (London, England) Apr 2024The number of older adults with head and neck squamous cell carcinoma (HNSCC) is continuously increasing. Older HNSCC patients may be more vulnerable to...
PURPOSE
The number of older adults with head and neck squamous cell carcinoma (HNSCC) is continuously increasing. Older HNSCC patients may be more vulnerable to radiotherapy-related toxicities, so that extrapolation of available normal tissue complication probability (NTCP) models to this population may not be appropriate. Hence, we aimed to investigate the correlation between organ at risk (OAR) doses and chronic toxicities in older patients with HNSCC undergoing definitive radiotherapy.
METHODS
Patients treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between 2009 and 2019 in a large tertiary cancer center were eligible for this analysis. OARs were contoured based on international consensus guidelines, and EQD2 doses using α/ß values of 3 Gy for late effects were calculated based on the radiation treatment plans. Treatment-related toxicities were graded according to Common Terminology Criteria for Adverse Events version 5.0. Logistic regression analyses were carried out, and NTCP models were developed and internally validated using the bootstrapping method.
RESULTS
A total of 180 patients with a median age of 73 years fulfilled the inclusion criteria and were analyzed. Seventy-three patients developed chronic moderate xerostomia (grade 2), 34 moderate dysgeusia (grade 2), and 59 moderate-to-severe (grade 2-3) dysphagia after definitive radiotherapy. The soft palate dose was significantly associated with all analyzed toxicities (xerostomia: OR = 1.028, dysgeusia: OR = 1.022, dysphagia: OR = 1.027) in the multivariable regression. The superior pharyngeal constrictor muscle was also significantly related to chronic dysphagia (OR = 1.030). Consecutively developed and internally validated NTCP models were predictive for the analyzed toxicities (optimism-corrected AUCs after bootstrapping: AUC=0.64, AUC=0.60, AUC=0.64).
CONCLUSIONS
Our data suggest that the dose to the soft palate is associated with chronic moderate xerostomia, moderate dysgeusia and moderate-to-severe dysphagia in older HNSCC patients undergoing definitive radiotherapy. If validated in external studies, efforts should be undertaken to reduce the soft palate dose in these patients.
Topics: Humans; Aged; Female; Male; Head and Neck Neoplasms; Organs at Risk; Palate, Soft; Radiation Injuries; Aged, 80 and over; Radiotherapy Dosage; Middle Aged; Squamous Cell Carcinoma of Head and Neck; Retrospective Studies; Radiotherapy Planning, Computer-Assisted
PubMed: 38689338
DOI: 10.1186/s13014-024-02426-5