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Journal of Clinical Medicine May 2024Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly...
Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral ( = 4) or Non-alcoholic steatohepatitis, NASH ( = 2). Tumor focality was multifocal ( = 4) and unifocal ( = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab ( = 4), nivolumab/ipilimumab ( = 1), and nivolumab as monotherapy ( = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.
PubMed: 38892779
DOI: 10.3390/jcm13113068 -
BMC Oral Health Jun 2024Surgical extraction of impacted third molars (ITM) often leads to postoperative discomfort including pain, swelling, and limited function. Steroids like dexamethasone... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Observational Study
Comparison of perineural and systemic dexamethasone use in impacted third molar surgeries in terms of anesthesia duration and postoperative complaints: a controlled, randomized observational study.
BACKGROUND
Surgical extraction of impacted third molars (ITM) often leads to postoperative discomfort including pain, swelling, and limited function. Steroids like dexamethasone (DXN) are commonly used in oral surgery to manage pain and inflammation. Various administration routes for DXN exist, including intravenous (IV), perineural (PN), and oral applications, each with its advantages. Previous studies have shown that adding DXN to local anesthetics can prolong anesthesia duration and reduce postoperative sequelae. However, comparative studies on IV and PN applications with inferior alveolar nerve block (IANB) of DXN in ITM surgeries are limited.
METHODS
This controlled, randomized observational study involved patients undergoing Class II position B ITM extraction. Patients were divided into three groups. IANB (1.8 ml of articaine hydrochloride + 1 ml of saline) was performed 1 h after IV-DXN (4 mg/ml DXN) was administered to the IV group. DXN along with IANB (1.8 ml of articaine hydrochloride + 1 ml of 4 mg/ml DXN) was applied to the PN group. Only IANB (1.8 ml of articaine hydrochloride + 1 ml of saline) was applied to the control group. Anesthesia duration was assessed as primary outcomes. Anesthesia duration was evaluated using a vitalometer from the molars. Secondary outcomes included postoperative pain and edema measured on the 1st, 3rd, and 7th days after surgery. Pain was evaluated postoperatively by using a visual analog scale. A p-value < 0.05 was considered statistically significant.
RESULTS
The study included 45 patients with similar demographic characteristics across groups. IV application significantly prolonged anesthesia duration compared to the control group. (p = 0.049) Both IV and PN administration of DXN reduced postoperative edema at 3rd (p = 0.048) and 7th day (p = 0.01). Post-procedure pain reduction was significant in the IV group (p = 0.011). On the other hand, it was observed that the pain did not decrease in the PN group at 3rd and 7th days compared to the control and IV groups.
CONCLUSIONS
PN and IV DXN administration prolonged anesthesia duration and reduced postoperative edema in ITM surgeries. However, PN DXN administration was associated with increased postoperative pain compared to IV DXN and control groups. Further studies comparing different doses and administration routes of DXN are needed to determine optimal strategies for managing postoperative discomfort in ITM surgeries.
TRIAL REGISTRATION
This study was conducted at Ahmet Keleşoğlu Faculty of Dentistry with the permission of Karamanoğlu Mehmetbey University Faculty of Medicine Ethics Committee (#04-2022/101). Trial registration is also available at clinicaltrail.gov. (NCT06318013, 26/05/2024).
Topics: Humans; Molar, Third; Dexamethasone; Tooth, Impacted; Male; Female; Pain, Postoperative; Tooth Extraction; Nerve Block; Adult; Anesthesia, Dental; Anesthetics, Local; Young Adult; Pain Measurement; Mandibular Nerve; Carticaine; Time Factors; Edema
PubMed: 38890655
DOI: 10.1186/s12903-024-04483-4 -
Head & Face Medicine Jun 2024The treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have...
BACKGROUND
The treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have been recognized driving the cancer progression and high expression levels cause poor outcomes in patients afflicted with OSCC. Integrin αvβ6 and its subunit integrin beta 6 (ITGB6) were discovered to enhance the invasiveness by providing beneficial effects on downstream pathways promoting the cancer progression. The objective of this study was to establish a CRISPR/Cas9-mediated knock out of ITGB6 in the human OSCC cell line HN and investigate the effects on the migration and proliferation ability.
METHODS
ITGB6 knock out was performed using the CRISPR/Cas9-system, RNPs, and lipofection. Monoclonal cell clones were achieved by limiting dilution and knock out verification was carried out by sanger sequencing and FACS on protein level. The effects of the knock out on the proliferation and migration ability were evaluated by using MTT and scratch assays. In addition, in silico TCGA analysis was utilized regarding the effects of ITGB6 on overall survival and perineural invasion.
RESULTS
In silico analysis revealed a significant impact of ITGB6 mRNA expression levels on the overall survival of patients afflicted with OSCC. Additionally, a significantly higher rate of perineural invasion was discovered. CRISPR/Cas9-mediated knock out of ITGB6 was performed in the OSCC cell line HN, resulting in the generation of a monoclonal knock out clone. The knock out clone exhibited a significantly reduced migration and proliferation ability when compared to the wildtype.
CONCLUSIONS
ITGB6 is a relevant factor in the progression of OSCC and can be used for the development of novel treatment strategies. The present study is the first to establish a monoclonal CRISPR/Cas9-mediated ITGB6 knockout cell clone derived from an OSCC cell line. It suggests that ITGB6 has a significant impact on the proliferative and migratory capacity in vitro.
Topics: Humans; Cell Movement; Cell Proliferation; Mouth Neoplasms; CRISPR-Cas Systems; Cell Line, Tumor; Carcinoma, Squamous Cell; Integrin beta Chains; Gene Knockout Techniques; Squamous Cell Carcinoma of Head and Neck; Neoplasm Invasiveness; Gene Expression Regulation, Neoplastic
PubMed: 38890650
DOI: 10.1186/s13005-024-00437-x -
Pancreas Jul 2024Although prevalent in 50%-90% of pancreatic ductal adenocarcinomas, the clinical relevance of "cancerization of ducts" (COD) remains unknown.
OBJECTIVES
Although prevalent in 50%-90% of pancreatic ductal adenocarcinomas, the clinical relevance of "cancerization of ducts" (COD) remains unknown.
METHODS
Pathologists retrospectively reviewed slides classifying prevalence of COD. Histopathological parameters, location of first recurrence, recurrence-free survival (RFS), and overall survival (OS) were collected from the institutional pancreatectomy registry.
RESULTS
Among 311 pancreatic ductal adenocarcinomas, COD was present in 216 (69.5%) and more prevalent in the cohort that underwent upfront surgery (75.3% vs 63.1%, P = 0.019). Furthermore, COD was associated with female gender (P = 0.040), advanced T stage (P = 0.007), perineural invasion (P = 0.014), lymphovascular invasion (P = 0.025), and R1 margin (P = 0.009), but not N stage (P = 0.401) or tumor differentiation (P = 0.717). In multivariable regression, COD was associated with less liver recurrence (odds ratio, 0.44; P < 0.005). This association was driven by the cohort of patients who had received preoperative treatment (odds ratio, 0.18; P < 0.001). COD was not predictive for RFS or OS.
CONCLUSIONS
Cancerization of ducts was not associated with RFS or OS. Currently underrecognized, standardized implementation into histopathological reports may have merit, and further mechanistic scientific experiments need to illuminate its clinical and biologic impact.
Topics: Humans; Carcinoma, Pancreatic Ductal; Male; Female; Pancreatic Neoplasms; Retrospective Studies; Aged; Middle Aged; Pancreatectomy; Neoplasm Recurrence, Local; Disease-Free Survival; Pancreatic Ducts; Clinical Relevance
PubMed: 38888841
DOI: 10.1097/MPA.0000000000002326 -
Journal of Clinical Pathology Jun 2024Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are...
AIMS
Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations.
METHODS
This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses.
RESULTS
Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates.
CONCLUSION
p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study's findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.
PubMed: 38886043
DOI: 10.1136/jcp-2024-209450 -
Annals of Surgery Open : Perspectives... Mar 2024To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR).
OBJECTIVE
To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR).
BACKGROUND
A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique.
METHODS
Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate.
RESULTS
A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50-6.75) and 6.82% (95% confidence interval: 5.08-8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis.
CONCLUSIONS
In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.
PubMed: 38883940
DOI: 10.1097/AS9.0000000000000369 -
Indian Journal of Otolaryngology and... Jun 2024Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and...
Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and treatment strategies for these tumors to improve patient outcomes. The audit included patients with salivary gland tumors detected through radiology or cytology. Patients underwent surgery, with some receiving adjuvant treatment. Demographic information, treatment interventions, and survival outcomes were analyzed using SPSS software. A total 89 as malignant salivart gland tumours were audited Malignant tumors were predominantly found in the parotid gland, with fewer cases in the minor salivary gland and submandibular gland.The median age of presentation was 47 years, and the majority of patients were male. The study examined various pathological and clinical factors, including tumor stage, nodal status, and the presence of facial palsy. Surgical procedures and histological types of tumors were documented. Adverse histological features like positive margins, lymph node positivity, lympho-vascular invasion, extracapsular spread, and perineural invasion were noted. POSTOP RT was administered to high-risk patients. Most malignant salivary gland tumors were found in the parotid gland, while minor salivary gland tumors were underrepresented in the audit. Surgical practices were diverse. Radiotherapy protocols were relatively standardized. The study found that certain histological features, such as lymph node positivity, margin positivity, lympho-vascular invasion, perineural invasion, and extracapsular spread, were associated with adverse effects on DFS and OS. The findings suggest that specific histological features, including LVI and ECE have emerged as independent prognostic factors for DFS and OS.
PubMed: 38883502
DOI: 10.1007/s12070-023-04348-2 -
Drug Design, Development and Therapy 2024Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.
BACKGROUND
Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine.
METHODS
A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 μg·kg (RD Group) or 1.0 μg·kg (RD Group), or intravenous (IV) dexmedetomidine 0.5 μg·kg·h (RD Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery.
RESULTS
(1) For the primary outcome, RD Group and RD Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RD Group, RD Group, and RD Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RD Group, RD Group and RD Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD Group, RD Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD Group showed an increased incidence of drowsiness.
CONCLUSION
Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 μg·kg) may be a more appropriate choice.
CLINICAL TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2200058982).
Topics: Humans; Dexmedetomidine; Double-Blind Method; Male; Nerve Block; Female; Middle Aged; Chronic Pain; Acute Pain; Pain, Postoperative; Aged; Ultrasonography, Interventional; Thoracoscopy; Lung Neoplasms; Adult; Administration, Intravenous
PubMed: 38882043
DOI: 10.2147/DDDT.S457334 -
Arkhiv Patologii 2024The purpose of this work was to evaluate gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the...
OBJECTIVE
The purpose of this work was to evaluate gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor.
MATERIAL AND METHODS
The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe.
RESULTS
In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (<0.05).
CONCLUSION
Amplification of the gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.
Topics: Humans; Male; Prostatic Neoplasms; Proto-Oncogene Proteins c-myc; Gene Amplification; Middle Aged; Aged; Genes, myc; Carcinoma, Acinar Cell
PubMed: 38881003
DOI: 10.17116/patol20248603130 -
Cancer Treatment and Research... Jun 2024Recently, some evidence emphasized the value of MSH2 and MSH6 inactivation and their hypermutation in predicting different cancers. The present consideration is to...
BACKGROUND
Recently, some evidence emphasized the value of MSH2 and MSH6 inactivation and their hypermutation in predicting different cancers. The present consideration is to evaluate the value of MSH2 and MSH6 protein deficient studied by the immunohistochemistry (IHC) method and the tumor behaviors and aggressiveness in prostatic carcinoma.
METHODS
This cross-sectional study was performed on 80 examples extricated from patients who endured prostate cancer and were planned for radical prostatectomy surgery. The expression levels of the genes were studied by IHC staining.
RESULTS
The deficiency in MSH2 and MSH6 expression was revealed in 10.0 % and 11.3 % of patients respectively, while the reduction of simultaneous expression in two genes was found in 6.2 % of patients. In the two subgroups with and without MSH2 and/or MSH6 staining, there was no difference in patients' mean age and history of prostate cancer. There was also no difference in tumor-related behaviors including combined Gleason grade group, tumor stage, vascular invasion, perineural invasion, and prostatic capsular invasion between the groups with and without gene loss.
CONCLUSION
The evaluation of the deficient rate of two genes among patients with prostate cancer to predict the tumor grade and its aggressive behavior needs further study in every population.
PubMed: 38870667
DOI: 10.1016/j.ctarc.2024.100826