Αρχειοθήκη ιστολογίου

Κυριακή 13 Φεβρουαρίου 2022

Reconstruction following transoral robotic surgery for head and neck cancer: Systematic review

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Abstract

We performed a systematic review to characterize reconstructive modalities and postoperative surgical outcomes following TORS resection. A search of the PubMed, SCOPUS, and EMBASE databases was conducted to identify studies describing patients undergoing reconstruction of TORS defects. Twenty-six studies met inclusion criteria, consisting of 260 patients who underwent TORS resection followed by reconstruction. Twenty-one studies reported tumor classification information, with TORS performed for 44 (23.0%) T1, 86 (45.0%) T2, 33 (17.3%) T3, and 28 (14.7%) T4 tumors. Eighteen distinct reconstructive modalities were described in the studies identified, including nine unique free flap types. The most commonly performed reconstruction was the radial forearm free flap (RFFF), accounting for 121/260 (46.5%) of reconstructions performed. Reported surgical complications included 5 pharyngocutaneous fistulae, 13 hemorrhagic complications, 24 infectious complications, and 5 free flap failures . Our findings demonstrate favorable surgical outcomes but minimal quantitative functional data to compare reconstructive options following TORS.

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The effect of cosmetic surgery on mental self-image and life satisfaction in women undergoing breast augmentation: An intermediate role of evaluating the surgery as one of the most important life events

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J Plast Reconstr Aesthet Surg. 2022 Jan 21:S1748-6815(22)00033-X. doi: 10.1016/j.bjps.2022.01.018. Online ahead of print.

ABSTRACT

AIM: To estimate changes in self-perception and satisfaction in women undegoing breast augmentation surgery (BAS).

METHODS: Using a quasi-experimental questionnaire study design, we enrolled a cohort of BAS women treated at a private clinic during a 5-year interval. The primary predictor variable was treatment (before/after). The main outcome variables included effect of considering breast augmentation as one of the most important life events on self-image (BAOMILE), and subjective evaluation of physical appearance and life satisfaction. Other study variables were demographic data. The Mann-Whitney and the Wilcoxon signed-rank tests were used to compare the outcomes between before and after the surgery. The Spearman rank correlation and the Pearson chi-squared test were computed to analyze the relatio nships among variables.

RESULTS: The sample consisted of 53 subjects (52.3% married; 40.9% from medium-sized towns) with a mean age of 33.2 ± 6.4 years (range, 21-46). Life satisfaction was significantly increased after BAS in the whole cohort (preop., 7.83 vs. postop., 8.42; P = .003; 95% CI, -0.95 to -0.22) as well as in the BAOMILE subgroup (preop., 7.87 vs. postop., 8.56; P = .011; 95% CI, -1.20 to -0.17). Within the BAOMILE subgroup, there was a positive correlation between the appearance assessment and the number of positive traits before surgery (ρ = 0.63; P = .002; 95% CI, 0.27-0.83) and life satisfaction after surgery (ρ = 0.480; P = .03; 95% CI, 0.06-0.74).

CONCLUSIONS: The results of this study suggest that BAS improves self-perception and life satisfaction of the patients. The psychologist's role in understating patient's motivation for cosmetic surgery and the revision of their attitudes towards expected effects require further investigations.

PMID: 35140045 | DOI:10.1016/j.bjps.2022.01.018

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Mitochondrial DHODH regulates hypoxia-inducible factor 1 expression in OTSCC

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Am J Cancer Res. 2022 Jan 15;12(1):48-67. eCollection 2022.

ABSTRACT

Oral tongue squamous cell carcinoma (OTSCC) was one of the most hypoxic tumors with unfavorable outcomes. Hypoxia-inducible factor-1 (HIF-1) signaling was associated with cancer proliferation, lymph node metastasis, angiogenesis and poor prognosis of OTSCC. Dihydroorotate dehydrogenase (DHODH) catalyzed the rate-limiting step in the de novo pyrimidine biosynthesis. The aim of the study was to explore the biological function of DHODH and investigate whether DHODH regulated HIF-1 signaling in OTSCC. Proliferation, migration and anoikis resistance were used to determine the function of DHODH. Western blot and luciferase activity assays were used to determine the regulatory role of DHODH on HIF-1. We found that increased DHODH expression was associated with advanced tumor stage and poorly differentiated tumor in head and neck cancer patients in The Cancer Genome Atlas (TC GA). DHODH enhanced the proliferation and aggressiveness of OTSCC. Moreover, DHODH prompted tumor growth and metastasis in vivo. DHODH promoted transcription, protein stability, and transactivation activity of HIF1A. DHODH-induced HIF1A upregulation in OTSCC can be reversed by reactive oxygen species (ROS) scavenger, indicating that DHODH enhanced HIF1A expression via ROS production. DHODH inhibitor suppressed DHODH-mediated ROS generation and HIF1A upregulation. Targeting DHODH using clinically available inhibitor, atovaquone, might provide a new strategy to treat OTSCC.

PMID:35141004 | PMC:PMC8822278

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Modulation of BRCA1 mediated DNA damage repair by deregulated ER-α signaling in breast cancers

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Am J Cancer Res. 2022 Jan 15;12(1):17-47. eCollection 2022.

ABSTRACT

BRCA1 mutation carriers have a greater risk of developing cancers in hormone-responsive tissues like breasts and ovaries. However, this tissue-specific incidence of BRCA1 related cancers remains elusive. The majority of the BRCA1 mutated breast cancers exhibit typical histopathological features of high-grade tumors, with basal epithelial phenotype, classified as triple-negative molecular subtype and have a higher percentage of DNA damage and chromosomal abnormality. Though there are many studies relating BRCA1 with ER-α (Estrogen receptor-α), it has not been reported whether E2 (Estrogen) -ER-α signaling can modulate the DNA repair activities of BRCA1. The present study analyzes whether deregulation of ER-α signaling, arising as a result of E2/ER-α deficiency, could impact the BRCA1 dependent DDR (DNA Damage Response) pathways, predominantly those of DNA-DSB (Dou ble Strand break) repair and oxidative damage response. We demonstrate that E2/E2-stimulated ER-α can augment BRCA1 mediated high fidelity repairs like HRR (Homologous Recombination Repair) and BER (Base Excision Repair) in breast cancer cells. Conversely, a condition of ER-α deficiency itself or any interruption in ligand-dependent ER-α transactivation resulted in delayed DNA damage repair, leading to persistent activation of γH2AX and retention of unrepaired DNA lesions, thereby triggering tumor progression. ER-α deficiency not only limited the HRR in cells but also facilitated the DSB repair through error prone pathways like NHEJ (Non Homologous End Joining). ER-α deficiency associated persistence of DNA lesions and reduced expression of DDR proteins were validated in human mammary tumors.

PMID:35141003 | PMC:PMC8822286

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ST3GAL2 knock-down decreases tumoral character of colorectal cancer cells in vitro and in vivo

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Am J Cancer Res. 2022 Jan 15;12(1):280-302. eCollection 2022.

ABSTRACT

Tumor cells have a modified glycosylation profile that promotes their evolution and/or their maintenance in the tumor. Sialylation is a type of glycosylation that is often altered in cancers. RNA-Seq database analysis revealed that the sialyltransferase gene ST3GAL2 is significantly overexpressed at all stages of colorectal cancer (CRC). ST3GAL2 sialylates both glycoproteins and glycolipids. The aim of this work was to investigate the involvement of ST3GAL2 in CRC. Using the HT29 tumor cell line derived from a stage II of CRC, we decreased the expression of ST3GAL2 by specific shRNA, and then characterized these cells by performing functional tests. We found that ST3GAL2 knock down (KD) significantly decreases tumor cell proliferation, cell migration and invasiveness properties in vitro. The cell cycle of these cells is affected with a ch ange in cell cycle distribution and an increase of cell apoptosis. The effect of ST3GAL2 KD was then studied in vivo, following xenografts into nude mice, in which the tumor progression was significantly reduced. This work demonstrates that ST3GAL2 is a major player in the behavior of colorectal tumor cells, by modifying the sialylation state of glycoproteins and glycolipids which remain to be specifically identified.

PMID:35141018 | PMC:PMC8822282

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Definitive radiation therapy and liver local therapy in de novo liver metastatic nasopharyngeal carcinoma: Large cohort study

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Abstract

Background

We aimed to evaluate patients suitable for definitive radiation therapy (DRT) and liver local therapy (LLT) in addition to palliative chemotherapy (PCT) among those with de novo liver metastatic nasopharyngeal carcinoma (lmNPC).

Methods

The overall survival (OS) and progression-free survival (PFS) rates were calculated and compared in 610 patients with lmNPC.

Results

Both the PCT+DRT and PCT+DRT+LLT groups had better survival outcomes than the PCT group. Among patients with complete response/partial response (CR/PR) after PCT, no significant differences in survival rates were observed between those treated with PCT+DRT and PCT+DRT+LLT (2-year PFS: 27.0% vs. 32.9%, p = 0.263). Among patients with progressive disease/stable disease (PD/SD) after PCT, significantly better survival rates were observed in patients treated with PCT+DRT+LLT.

Conclusions

DRT might benefit patients with lmNPC regardless of the tumor response after PCT. For patients with CR/PR, LLT might not be needed. For patients with PD/SD, LLT might improve survival outcomes.

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Nasal reconstruction with local flaps versus grafts: Long term perspectives

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J Plast Reconstr Aesthet Surg. 2022 Feb 1:S1748-6815(22)00025-0. doi: 10.1016/j.bjps.2022.01.010. Online ahead of print.

NO ABSTRACT

PMID:35144904 | DOI:10.1016/j.bjps.2022.01.010

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Understanding Public Perceptions Regarding Cochlear Implant Surgery in Adults

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Otol Neurotol. 2022 Mar 1;43(3):e331-e336. doi: 10.1097/MAO.0000000000003439.

ABSTRACT

BACKGROUND AND OBJECTIVE: Approximately 6% of adults eligible for cochlear implantation (CI) undergo surgery. This study aims to understand how general perceptions about CI contribute to barriers causing this low utilization rate.

METHODS: Participants completed an online survey regarding their perceptions about cochlear implantation. They were asked to rank CIQOL-10 Global priorities and corresponding risk tolerance for minor complications (changes in taste, vertigo) and major complications (infections requiring hospitalization, meningitis, reimplantation, facial paralysis, and cerebrospinal fluid [CSF] leak).

RESULTS: A total of 615 responses (female 55%, mean age 39 years [range 20-78]) were included. Respondents identified issues with insurance (46%) and fear of undergoing surgery (21%) as barriers preventing eligible adults from receiving C I. Regarding surgical risk, respondents significantly underestimated rates of minor complications (p < 0.0001) and almost all major complications (all p < 0.0001) while overestimating rates of serious infections and need for reimplantation (both p < 0.005). The ability to hear strangers in noisy environments was identified as the highest priority for CI (26%). Individuals who knew someone with a cochlear implantation were willing to tolerate higher rates of all minor and major complications (all p < 0.05). Healthcare workers were similarly willing to tolerate significantly higher rates of meningitis, facial paralysis, and CSF leak to achieve their highest priority (all p < 0.05).

CONCLUSIONS: Respondents identify insurance coverage and fear of surgery as primary reasons for low utilization of adult CI in the United States. However, healthcare workers or those who knew someone with a cochlear implantation indicated significantly higher rates of risk tolerance to achieve their highest quality of life priorities, indicating the potential that the benefits of cochlear implantation are underappreciated in the general population.

PMID:35147605 | DOI:10.1097/MAO.0000000000003439

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Irradiated fibroblasts increase interleukin-6 expression and induce migration of head and neck squamous cell carcinoma

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by Shinsuke Suzuki, Satoshi Toyoma, Yohei Kawasaki, Takechiyo Yamada

Background

Cytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts.

Methods

We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody.

Results

Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody.

Conclusion

These results show that fibroblasts survive irradiation and indu ce the migration ability of HNSCC cells through increased secretion of IL-6.

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Selected by bioinformatics and molecular docking analysis, Dhea and 2–14,15-Eg are effective against cholangiocarcinoma

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by Lei Qin, Jun Kuai, Fang Yang, Lu Yang, Peisheng Sun, Lanfang Zhang, Guangpeng Li

Object

To identify novel targets for the diagnosis, treatment and prognosis of cholangiocarcinoma, we screen ideal lead compounds and preclinical drug candidates with MYC inhibitory effect from the ZINC database, and verify the therapeutic effect of Dhea and 2–14,15-Eg on cholangiocarcinoma.

Methods

The gene expression profiles of GSE132305, GSE89749, and GSE45001 were obtained respectively from the Gene Expression Omnibus database. The DEGs were identified by comparing the gene expression profiles of cholangiocarcinoma and normal tissues. GO, KEGG analysis and PPI network analyses were performed. LibDock, ADME and toxicity prediction, molecular docking and molecular dynamics simulations were used to identify potential inhibitors of MYC. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay and Western blotting were performed to verify the therapeutic effect of Dhea and 2–14,15-Eg.

Results

PPI network analysis showed that ALB, MYC, APOB, IGF1 and KNG1 were hub genes, of which MYC was mainly studied in this study. A battery of computer-aided virtual techniques showed that Dhea and 2–14,15-Eg have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6, as well as could exist stably in natural circumstances. In vitro assays showed that Dhea and 2–14,15-Eg inhibited cholangiocarcinoma cellular viability, proliferation, and migration inhibiting expression of MYC.

Conclusion

This study suggested that Dhea and 2–14,15-Eg were novel potential inhibitors of MYC targeting, as well as are a promising drug in dealing with cholangiocarcinoma and have a perspective application.

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Vertical rectus abdominis myocutaneous flap to reconstruct thigh and groin defects: A retrospective cohort and systematic review

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J Plast Reconstr Aesthet Surg. 2022 Jan 19:S1748-6815(22)00028-6. doi: 10.1016/j.bjps.2022.01.015. Online ahead of print.

ABSTRACT

BACKGROUND: The vertical rectus abdominis myocutaneous (VRAM) flap is one of the options for soft-tissue reconstruction in the groin and thigh. The aim of this study is to evaluate the clinical outcomes, risk factors for complications, and the utility of using mesh to prevent abdominal hernia.

METHODS: A retrospective review of patients who underwent VRAM flap reconstruction to reconstruct proximal thigh and groin defects from 1997 to 2018 was performed. Data regarding patient demographics, surgical characteristics, and postoperative outcomes were collected. Proportional hazard regression analysis was performed to assess the association of the risk of recipient site complications. A systematic review was performed to assess the outcomes and summarize the evidence from published studies.

RESULTS: Fifty-three patients were identified and included in this study. In most of the cases, the procedures were performed after tumor resection (77%) and in the rest of the cases, they were performed for chronic complicated wounds (23%). Twenty-five (47.2%) patients developed complications. Intraoperative and postoperative radiotherapy, chronic kidney disease, history of prior tumor resection, and reconstructions of chronic complicated wounds were associated with an increased risk of recipient site complications. A systematic review identified 9 articles, for a total of 189 reconstructions. The pooled complications and failure rates were 31.2% and 2.1%, respectively. Stratified analysis showed that the rate of abdominal hernia was similar in patients with mesh (16.7%) and in patients with primary closure only (15.1%; p = 0.761).

CONCLUSION: Defects in the groin or proximal thigh can be treated successfully with the VRAM flap. Although wound complications and hernia rates are high, the reconstruction failure rate is low.

PMID:35148978 | DOI:10.1016/j.bjps.2022.01.015

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