Capsule Infiltration Research Articles

MicroRNA-26a deficiency attenuates the severity of frozen shoulder in a mouse immobilization model.

The main pathogenesis of the frozen shoulder is thought to be the inflammation of the intra-articular synovium and subsequent fibrosis of the shoulder joint capsule. However, the molecular pathogenesis of the frozen shoulder is still unknown. A class of noncoding RNAs, microRNAs contribute to various diseases including musculoskeletal diseases. MicroRNA-26a (miR-26a) has been reported to be associated with fibrosis in several organs. This study aims to reveal the role of miR-26a on fibrosis in the shoulder capsule using a frozen shoulder model in miR-26a deficient (miR-26a KO) mice. MiR-26a KO and wild-type (WT) mice were investigated using a frozen shoulder model. The range of motion (ROM) of the shoulder, histopathological changes such as synovitis, and fibrosis-related gene expression in the model mice were evaluated to determine the role of miR-26a. In WT mice, both inflammatory cell infiltration and thickening of the inferior shoulder joint capsule were observed after 1 week of immobilization, and this thickening further progressed over the subsequent 6 weeks. However, the immobilized shoulder in miR-26a KO mice consistently exhibited significantly better ROM compared with WT mice at 1 and 6 weeks, and histological changes were significantly less severe. The expression of inflammation- and fibrosis-related genes was decreased in the miR-26a KO mice compared with WT mice at 1 and 6 weeks. Together, miR-26a deficiency attenuated the severity of frozen shoulder in the immobilization model mouse. The present study suggests that miR-26a has the potential to be a target miRNA for therapeutic approach to frozen shoulder.

Oral cavity salivary gland pleomorphic adenoma: a histomorphological case series

BackgroundPleomorphic adenoma (PA), the most common benign salivary gland epithelial lesion, has a biphasic epithelial-mesenchymal pattern and great histopathological diversity. MethodsThis study's objective was to conduct a retrospective clinicopathological analysis, focusing on the histopathology characteristics of salivary gland PA. ResultsThere were ten cases of pleomorphic adenoma. The mean age was 33.5 years and no gender predilection was observed. All the patients presented with an asymptomatic mass and the duration of presentation was 31.2 ± 19.4 months. The cellular subtype (50 %) of PA was the most common. Capsular infiltration and incomplete capsules occurred in 20 % of cases. All the cases had round (100 %) and myxoid stroma.The cellular subtype was more common in the major salivary glands; showed capsular abnormalities (incomplete capsule, absent capsule, and tumor infiltration); and had more plasmacytoid, angular, spindled non-luminal cells as well as inflammation and cystic degeneration. The classic subtype had more clear and oncocytic cells along with sebaceous and squamous differentiation. The stroma-rich subtype had the shortest duration of complaints (three months) and showed giant cell reaction. ConclusionsThese findings confirm previous studies on the clinicopathological features of pleomorphic adenomas and highlight important morphologic characteristics like capsular invasion and squamous metaplasia, which can otherwise indicate malignancy.

Follicular dendritic cell sarcoma arising from the lymph node of the pancreatic head: a case report with literature review.

A 72-year-old man was referred to our hospital for the examination of a pancreatic head mass. Abdominal computed tomography revealed a contrasted 8-cm-diameter tumor extending from the dorsal pancreatic head to the porta hepatis. The preoperative diagnosis was challenging due to the absence of specific imaging findings and the inability to perform a biopsy. Positron emission tomography/computed tomography and diffusion-weighted imaging suggested a malignant tumor originating from the organs surrounding the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed, as dissection from the pancreatic head proved unfeasible. Pathological examination identified the tumor as an enlarged lymph node consisting of pleomorphic large cells forming clusters, positive for follicular dendritic cell markers cluster of differentiation (CD) 21 and CD23. No evidence of tumor capsule infiltration, other organ infiltration, or metastasis to other lymph nodes was observed. The final diagnosis was nodal follicular dendritic cell sarcoma (FDCS) originating from the pancreatic head lymph nodes. No recurrence occurred at 3years postoperatively with no postoperative treatment. Intraperitoneal nodal FDCS is extremely rare, and occasionally, it can lead to postoperative recurrence and progression. It is crucial to differentiate neoplastic lymph node enlargement around the pancreatic head from nodal FDCS.

Impact of Brentuximab Vedotin in Patients with Breast Implant-Associated Anaplastic Large Cell Lymphoma with Capsule Infiltration Requiring Chemotherapy

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T-cell lymphoma most frequently arising around a textured surface breast implant. It has been shown that capsule infiltration (T2, T3 and T4 of the TNM staging system) was an adverse prognostic factor. In this context, chemotherapy (with or without brentuximab vedotin [BV]) may be proposed, considering other factors such as metastatic disease or incomplete resection. Furthermore, the need for adjuvant chemotherapy in patients with stage IIA (T4N0M0) and complete en-bloc excision without residual disease is debated. Aim: To assess the management of BIA-ALCL with capsule infiltration, in particular: 1) To assess the impact of BV in those patients; 2) To evaluate the need for adjuvant chemotherapy in patients with stage IIA and complete en-bloc excision without residual disease. Methods: Since 2016, a national multidisciplinary meeting has been implemented by the French National Cancer Institute (NCI) to optimize management of patients with BIA-ALCL, particularly those with advanced disease. Meanwhile, a national registry has been set up by the LYSA, in collaboration with health authorities. Central pathological review has been carried out within the French NCI-labeled Lymphopath network. Results: From 2009 to 2023, 125 patients with BIA-ALCL were recorded, of which 111 (94 from France and 17 from Belgium) had complete data and were included in the present analysis. Overall, median age at diagnosis of BIA-ALCL was 58 years (24-82 years). Reasons for initial implantation were breast cancer reconstruction (n=54; 49%), cosmetic (n=45; 41%) or other (n=12; 10%). The median interval from first implantation to diagnosis of BIA-ALCL was 12.3 years (4-40 years). The median number of implants in the breast involved by BIA-ALCL was 2 (1-8), including at least one silicone implant in 95 (86%) patients, and at least one textured implant in all informative cases (n=102; Most often Allergan Biocell implants). At diagnosis of BIA-ALCL, 78/110 (71%) patients presented with periprosthetic effusion only, 20 (18%) had effusion and a breast mass, 6 (5.5%) had a breast mass only, and 6 (5.5%) had neither. At pathological examination of the capsule, T-stage was T1 (confined to effusion or a layer on luminal side of capsule) in 73/111 (66%) cases, T2-T3 (capsule infiltration) in 5 (4.5%) cases, T4 (lymphoma infiltrates beyond the capsule) in 32 (29%) cases, and unclassifiable in 1 case. Moreover, 18/111 (16%) patients had at least one non-breast extranodal involvement. Among the 36 patients with capsule infiltration (5 T2-T3 and 31 T4), 13 (including 11 T4) were treated with BV-CH(E)P regimen, 12 (all T4) with a CHOP/CHOP-like regimen, and 11 (including 8 T4) did not receive any chemotherapy. The main reasons for receiving chemotherapy were metastatic disease, incomplete resection, or no surgery. Patients who did not receive chemotherapy had a localized disease (3 stage IB/IC and 8 stage IIA) with complete en-bloc excision and no residual disease. Patients treated with BV-CH(E)P regimen and CHOP/CHOP-like regimen had similar characteristics without significant differences regarding age, clinical presentation, stage and surgery. After a median follow-up of 47 months from BIA-ALCL diagnosis, for BV-CH(E)P and CHOP/CHOP-like groups, the respective 4-year PFS rates were 100% and 57% (p=0.01), and the respective 4-year OS rates were 100% and 73% (p=0.07). Regarding the 11 patients who did not receive chemotherapy, 4-year PFS and OS were both 75%, which corresponds to a single event being a death without progression occurring more than 3 years after the diagnosis of lymphoma (4-year lymphoma-specific survival was 100%). Conclusions: 1) In patients with capsule infiltration requiring chemotherapy, BV-CH(E)P regimen was associated with improved PFS and OS compared with CHOP/CHOP-like regimen; 2) Patients with stage IIA and complete en-bloc excision without residual disease had favorable outcome without the need for adjuvant chemotherapy. These results should be confirmed prospectively.

Pain Management, Functional Recovery, and Stress Response Expressed by NLR and PLR after the iPACK Block Combined with Adductor Canal Block for Total Knee Arthroplasty-A Prospective, Randomised, Double-Blinded Clinical Trial.

This study aimed to investigate pain management, functional recovery, and stress response expressed by the neutrophile-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) after the popliteal artery and posterior knee capsule infiltration (iPACK) block combined with adductor canal block (ACB) in total knee arthroplasty (TKA). This was a prospective, double-blinded, randomised, controlled trial in a tertiary referral hospital. Three hundred and sixty-six patients were randomly allocated into the sham block group and iPACK combined with the ACB group. The primary outcome was postoperative pain scores. The secondary outcomes were opioid consumption, functional recovery expressed by a range of motion, and quadriceps strength. Also, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. There were significant differences between the sham block and iPACK + ACB group in pain scores p < 0.0001 at all time points. Therefore, there was a significant difference in opioid consumption (p < 0.0001) and functional recovery (p < 0.0001). Also, NLR and PLR levels 12 h (p < 0.0001) and 24 h (24 h) after surgery (p < 0.0001) were much lower in the iPACK + ACB group. After total knee arthroplasty, the iPACK combined with ACB block group improved pain management, functional recovery, and stress response. Therefore, we strongly recommend this technique as a part of a multimodal analgesia protocol in knee surgery.

Ultrasound Guided Infiltration of Popliteal Artery and Capsule of Knee [IPACK] versus IPACK with Adductor Canal Block [ACB] for Postoperative Knee Surgery Analgesia: A Comparative Study

Ultrasound Guided Infiltration of Popliteal Artery and Capsule of Knee [IPACK] versus IPACK with Adductor Canal Block [ACB] for Postoperative Knee Surgery Analgesia: A Comparative Study

Primary Total Knee Replacement: A Recipe for Dry Dressing.

To evaluate surgical outcomes using sets of techniques to achieve single dry dressing for two weeks post total knee replacement (TKR) at Dr. Sulaiman Al-Habib Hospital, Riyadh, Saudi Arabia. A prospective study comprised of 110 consecutive unilateral total knee replacements was conducted at the orthopedic department of Dr. Sulaiman Al-Habib Hospital, Suwaidi, Riyadh, KSA. Patients of both genders underwent knee replacement surgery due to primary knee osteoarthritis, Kellgren-Lawrence grades 3 and 4. Routine investigations and fitness evaluations of patients were carried out preoperatively. Preoperative minimal use of a tourniquet and release prior to arthrotomy closure; intravenous tranexamic acid, no drains; capsule infiltration with local anesthetics without adrenaline; tight closure with barbed sutures up to the skin in three layers; skin glue; Aquacel dressing; adductor canal block; and continuation of oral anticoagulant for four weeks. A total of 110 cases were included, of which 81 (73.6%) were females and 29 (26.4%) were males. The mean age of the study population was 60.5+10.3 years (48 to 88 years). The mean BMI in our patients was 30.57+10.5 kg/m2. Most patients were morbidly obese 13 (30.95%). The mean preoperative Hb% was 13.07+1.6 g/dl, while the mean postoperative Hb% was 12.58+1.9 mg/dl with a p-value of 0.28, which was non-significant statistically. Only two patients needed a change of Aquacel wound dressing for ooze. None of our patients developed deep venous thrombosis (DVT) or an infection. A sequential use of sets of techniques is observed to be associated with improved outcomes in terms of blood loss, wound infection, mobility, and patient satisfaction, leading to the ultimate end point of dry Aquacel wound dressing.

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision‐making of thyroid nodules

A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B-Raf proto-oncogene) mutation (BRAFV600E ) positivity and fine-needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology. Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAFV600E using an amplification-refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination. Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAFV600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAFV600E analysis alone. Combining methods variably improved diagnostic performance. BRAFV600E was not associated with capsule infiltration, neurovascular infiltration, mono- or multifocal PTC, lymph node metastasis, or clinical stage. The diagnostic performance of preoperative BRAFV600E determination was better than that of the BSRTC-FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

Analgesic efficacy of selective tibial nerve block versus partial local infiltration analgesia for posterior pain after total knee arthroplasty: a randomized, controlled, triple-blinded trial

BackgroundThe adductor canal block provides pain relief on the anterior aspect of the knee after arthroplasty. Pain on the posterior aspect may be treated either by partial local infiltration analgesia of the posterior capsule or by a tibial nerve block. This randomized, controlled, triple-blinded trial tests the hypothesis that a tibial nerve block would provide superior analgesia compared to posterior capsule infiltration in patients scheduled for total knee arthroplasty under spinal anesthesia with an adductor canal block. MethodsSixty patients were randomized to receive either infiltration of the posterior capsule by the surgeon with ropivacaine 0.2%, 25 mL, or a tibial nerve block with 10 mL of ropivacaine 0.5%. Sham injections were performed to guarantee proper blinding. The primary outcome was intravenous morphine consumption at 24 h. Secondary outcomes included intravenous morphine consumption, pain scores at rest and on movement, and different functional outcomes, measured at up to 48 h. When necessary, longitudinal analyses were performed with a mixed-effects linear model. ResultsThe median (interquartile range) of cumulative intravenous morphine consumption at 24 h was 12 mg (4–16) and 8 mg (2–14) in patients having the infiltration or the tibial nerve block respectively (p = 0.20). Our longitudinal model showed a significant interaction between group and time in favor of the tibial nerve block (p = 0.015). No significant differences were present between groups in the other above-mentioned secondary outcomes. ConclusionA tibial nerve block does not provide superior analgesia when compared to infiltration. However, a tibial nerve block might be associated with a slower increase in morphine consumption over time.

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach.

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = -0.87, p < 0.001). Kaplan-Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

Local Infiltrations in Patients with Radiculopathy or Chronic Low Back Pain Due to Segment Degeneration-Only A Diagnostic Value?

The purpose of this study was to investigate the differences in the therapeutic effectiveness of CT-assisted infiltration of a local anesthetic + corticosteroid between nerve root and facet joint capsule in patients with chronic complaints. In this prospective trial with a 12-month follow-up, a total of 250 patients with chronic low back pain and radiculopathy were assigned to two groups. In the first group, patients with specific lumbar pain due to spondyloarthritis received periarticular facet joint capsule infiltration (FJI). In the second group, patients with monoradicular pain received periradicular infiltration (PRI) via an extraforaminal selective nerve block. Clinical improvement after FJI and PRI regarding pain (NRS), function (ODI), satisfaction (McNab), and health related quality of life (SF-36) were compared. Minimally clinically important difference (MCID) served as the threshold for therapeutic effectiveness evaluation. A total of 196 patients were available for final analysis. With respect to the pain reduction and functional improvement (ODI, NRSoverall, and NRSback), the PRI group performed significantly better (ptreatment < 0.001) and longer over time (ptreatment × time 0.001) than the FJI group. Regarding pain and function, only PRI demonstrated a durable improvement larger than MCID. A significant and durable therapeutic value was found only after receiving PRI but not after FJI in patients with chronic pain.

Unilateral Surgery for Medullary Thyroid Carcinoma: Seeking for Clinical Practice Guidelines

Optimized preoperative diagnostic tools with calcitonin tests, ultrasound features, functional imaging modalities, and genetic testing to detect hereditary forms have led to an increased rate of earlier diagnosis and surgery for medullary thyroid cancer (MTC). This helps to adapt the primary surgery to the tumor stage and avoid surgical overtreatment for localized tumor growth, i.e., deviating from the regularly recommended thyroidectomy with bilateral central lymph node dissection in favor of a limited unilateral approach. To limit primary surgical therapy, it is crucial that the MTC is clinically unifocal, sporadic, and confined to the thyroid, and that calcitonin levels indicate biochemical recovery after surgery. The main requirement for such a limited approach is the availability of frozen section studies that reliably indicate (i) R0 resection of the MTC, (ii) absence of infiltration of the organ capsule, (iii) lack of desmoplasia (i.e., evidence of the metastatic potential of the MTC), (iiii) absence of contralateral disease or precancerous lesions. Informed consent is mandatory from the patient, who has been fully informed of the advantages, disadvantages, and potential risks of not undergoing the “classic” surgical procedure. The aim of this article is to review the guidelines for the management of early-stage MTC.

From LI-RADS Classification to HCC Pathology: A Retrospective Single-Institution Analysis of Clinico-Pathological Features Affecting Oncological Outcomes after Curative Surgery.

Background: The latest Liver Imaging Reporting and Data System (LI-RADS) classification by the American College of Radiology has been recently endorsed in the American Association for the Study of Liver Disease (AASLD) guidelines for Hepatocellular carcinoma (HCC) management. Although the LI-RADS protocol has been developed as a diagnostic algorithm, there is some evidence concerning a possible correlation between different LI-RADS classes and specific pathological features of HCC. We aimed to investigate such radiological/pathological correlation and the possible prognostic implication of LI-RADS on a retrospective cohort of HCC patients undergoing surgical resection. Methods: We performed a retrospective analysis of the pathological characteristics of resected HCC, exploring their distribution among different LI-RADS classes and analyzing the risk factors for recurrence-free, overall and cancer-specific survival Results: LI-RADS-5 (LR-5) nodules showed a higher prevalence of microvascular invasion (MVI), satellitosis and capsule infiltration, as well as higher median values of alpha-fetoprotein (αFP) compared to LI-RADS-3/4 (LR-3/4) nodules. MVI, αFP, satellitosis and margin-positive (R1) resection resulted as independent risk factors for recurrence-free survival, while LI-RADS class did not exert any significant impact. Focusing on overall survival, we identified patient age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Model for End Stage Liver Disease (MELD) score, αFP, MVI, satellitosis and R1 resection as independent risk factors for survival, without any impact of LI-RADS classification. Last, MELD score, log10αFP, satellitosis and R1 resection resulted as independent risk factors for cancer-specific survival, while LI-RADS class did not exert any significant impact. Conclusions: Our results suggest an association of LR-5 class with unfavorable pathological characteristics of resected HCC; tumor histology and underlying patient characteristics such as age, ECOG-PS and liver disease severity exert a significant impact on postoperative oncological outcomes.

Waiving Subsequent Complete Lymph Node Dissection in Melanoma Patients with Positive Sentinel Lymph Node Does Not Result in Worse Outcome on 20-Year Analysis.

Simple SummaryThe aim of the present study was to investigate long-term outcomes of melanoma patients who had micrometastasis on sentinel lymph node (SLN) biopsy. We focused on the comparison between melanoma patients with and without complete lymph node dissection (CLND) following a positive SLN biopsy result. Patients without CLND did not significantly differ from patients with CLND in regard to age, gender, tumor thickness, tumor ulceration, capsule infiltration of SLN, and invasion level of SLN. On 10-year analysis, we did not observe a significantly increased risk for melanoma relapse or melanoma-specific death in patients who did not undergo CLND after the detection of micrometastases on SLN biopsy. On 20-year analysis, again, the patients without CLND had no significantly increased risk of melanoma relapse and worse melanoma-specific survival. Hence, our 10-year survival data confirm the current notion that waiving CLND in SLN-positive patients does not result in clinical disadvantages with respect to melanoma-specific survival. For the first time, we demonstrate on 20-year survival analysis that relapse rates and melanoma-specific survival does not significantly differ between patients with or without CLND on long-term follow-up.Complete lymph node dissection (CLND) following positive sentinel lymph node (SLN) biopsy has been the standard of care for decades. We aimed to study melanoma patients with an emphasis on the outcome of patients with versus without CLND following positive SLN biopsy. SLN-positive patients with or without CLND were compared regarding important prognostic clinical and histological characteristics. Ten-year and 20-year survival curves for melanoma relapse and melanoma-specific survival (MSS) were determined by the Kaplan-Meier method and Cox proportional-hazards regression. We studied 258 patients who had micrometastases in their SLN biopsy. CLND was performed in 209 of 258 patients (81%). Hence, in 49 of 258 patients (19%) with SLN micrometastases, CLND was not performed. These patients did not significantly (p > 0.05) differ from patients with CLND in regard to age, gender, tumor thickness, tumor ulceration, capsule infiltration of SLN, or invasion level of SLN. On 10-year analysis, we did not observe a significantly increased risk for melanoma relapse and worse in MSS in patients who did not undergo CLND (hazard ratio: 1.1 (95% CI 0.67 to 1.7) and 1.1 (95% CI 0.67 to 1.9), respectively). On 20-year survival analysis, we confirmed that the risk of melanoma relapse and impaired MSS does not significantly increase in patients without CLND (hazard ratio: 1.2 (95% CI 0.8 to 1.9) and 1.3 (95% CI 0.8 to 2.3), respectively). On 10-year as well as 20-year multivariable follow-up analysis (including several important prognostic factors), Cox proportional-hazards regression showed that the status of CLND did not remain in the regression model (p > 0.1). Our 10-year data give conclusive support to previous investigations indicating that waiving CLND in patients with SLN micrometastases does not affect MSS. More importantly, our long-term follow-up data confirm for the first time the 10-year survival data of previous investigations.

Analysis of survival rates and prognosis of hepatoblastoma in children: a retrospective study from a single center in China

Hepatoblastoma (HB) is the most common liver cancer in children, this study aims at analyzing the prognostic factors affecting the survival rates and summarizing the treatment experience. In this study, we reviewed patients with primary HB under the age of 14 years who underwent complete tumor resection from June 1997 to March 2019. The data of 72 patients were collected. Survival analysis was performed by Kaplan-Meier, multivariate Cox proportional hazards regression and linear mixed model for repeated measures (LMMRM). The 5-year and the 10-year event-free survival (EFS) of all patients were 78.2% and 73%, respectively. Both the 5-year and 10-year overall survival (OS) were 85.7%. Kaplan-Meier survival analysis showed that patients with tumor capsule infiltration (TCI) and patients with surgical margin less than 1 cm may also have a good prognosis. The Cox proportional hazards regression model analysis results were similar to the Kaplan-Meier analysis results. LMMRM analysis showed that there were significant differences in platelet, alpha-fetoprotein, C-reactive protein and hemoglobin values after surgery in the metastasis group (P < 0.05). This study suggests that patients with TCI or narrow surgical margin (<1 cm) may also have a good prognosis, and the risk stratification of HB can be used as the latest grading standard to evaluate the prognosis of patients.

Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis.

Background:Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients.Methods:We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test.Results:HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration.Conclusions:HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.

INTRAORAL PLEOMORPHIC ADENOMA: A CLINICOPATHOLOGIC STUDY OF A CASE SERIES

Objective The aim of this study was to describe the clinicopathologic features of 21 cases of intraoral pleomorphic adenoma (PA). Study Design Between 2000 and 2016, all patients diagnosed with intraoral PA were retrieved and histopathologic slides stained with hematoxylin and eosin were reviewed. All tumors were classified histologically according to the Seifert et al. Results The palate was the most common site (42.8%), with a slight predilection for females (52.4%) and a mean age of 36.68 years. Histopathologic analyses revealed a diversity of histologic patterns. Plasmacytoid (85.7%), fusiform (38.1%), epithelioid (9.5%), mucous (19%), and oncocytic (28.5%) cells were observed, as well as fibrous (95.2%), myxoid (66.7%), and chondromyxoid (28.6%) stroma. Most tumors were encapsulated (71.5%). Squamous (57.1%), adipose (47.6%), sebaceous (14.3%), and osseous (14.3%) metaplasias were found. A small group presented with pleomorphism (23.8%), increased mitotic activity (14.3%), necrotic areas (9.5%), and capsule infiltration (4.3%). According to the Seifert's classification, most PAs were classified as subtype III (47.6%), followed by subtypes I and II (23.8%), and subtype IV (4.8%). Conclusions These results confirm the morphologic diversity of PAs. The knowledge of these detailed microscopic features is essential to a correct diagnosis and adequate treatment.

Immunohistochemical Study of Cell Proliferation in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common primary liver cancer, with a poor prognosis, is the fifth most common cancer in men and the seventh in women. The study was made on 32 surgically removed liver carcinomas. In order to compare results, we included a group of non-tumor lesions obtained by liver biopsy. Assessment of the proliferative activity of the studied liver lesions was made using immunohistochemical stains with the monoclonal Ki-67 antibody, clone MIB-1 ready-to-use (DAKO Cytomation CA, USA), in the LSAB-HRP work system. To appreciate the proliferation index of Ki-67 (PI Ki-67), we used the semi-automated method of counting the nuclei on digital images. The statistical analysis was performed using SPSS software, Version 20.0 (IBM SPSS Statistics) and Microsoft Office Excel 2007. Mean value of Ki-67 index was 0.4 � 0.2 in normal liver, 3.52 � 0.2 in non-tumor liver lesions and 13.4�7.7 in HCC (p [ 0.001). In chronic hepatitis, PI Ki-67 varied between 2.5 and 5.8 %, with a mean value of 5.2% in portal chronic hepatitis and 5.5% in active chronic hepatitis with cirrhotic evolution. In HCC, the values of Ki-67 index were between 0.7% and 52%, with a mean of PI Ki-67 of 13.43�7.7. 66.6% of HCC associated with hepatitis B virus infection and those developped from a cirrhotic lesion had a high Ki-67 score (p = 0.1). The results we obtained showed: a low Ki-67 score in patients with well-differentiated HCC (G1) (p[0.001), with or without capsule infiltration (p = 0.003); high PI Ki-67 in 33.33% of HCC detected in the right hepatic lobe and those extended bilaterally at the moment of diagnosis (p = 0.142) and a significant relationship between high Ki-67 score and vascular invasion (p [ 0.001), the presence of intrahepatic metastasis being correlated with a high proliferative rate (p [ 0.001). Differences between the proliferation rate of HCC and non-tumor liver lesions (p [ 0.001) show that the uncontrolled division of tumor cells can play an important role in the developpment of HCC.

Haemoperitoneum Due to Spontaneous Rupture of a Liver Metastasis.

Spontaneous rupture of a liver metastasis is a life-threatening complication of metastatic liver disease. Although metastatic liver lesions are much more common than primary tumours, spontaneous rupture of a liver metastasis is rare. Therapeutic decisions must take into account the extent of metastatic liver disease and the patient’s performance status. Transarterial embolization may be considered in cases of ongoing haemorrhage despite initial conservative measures. We describe a case of haemoperitoneum due to spontaneous rupture of a liver metastasis in a 72-year-old patient with carcinoma of unknown origin who responded well to conservative management.LEARNING POINTSSpontaneous rupture of a liver metastasis is a rare but potentially life-threatening complication of metastatic cancer to the liver; risk factors include subcapsular location, rapid tumour growth and tumour necrosis (spontaneous or due to chemotherapy).Unexplained fever often precedes the spontaneous rupture, probably reflecting tumour necrosis or infiltration of the liver capsule, and may raise clinical suspicion for the diagnosis.Transarterial embolization may be considered in cases of ongoing haemorrhage despite initial conservative measures.

Histopathological Findings of Intraoral Pleomorphic Adenomas: A Retrospective Study of a Case Series.

The aim of this study was to describe the clinicopathological features of 21 cases of intraoral pleomorphic adenoma (PA), with emphasis on histopathological findings. Between 2000 and 2016, all patients diagnosed as intraoral PA were retrieved and histopathological slides stained with hematoxylin and eosin reviewed to confirm the diagnosis. All tumors were classified histologically according to Seifert et al (1980). The clinical and histopathological variables were analyzed using the Fisher's exact test, considering a significance level of 5% (P < .05). Plasmacytoid (85.7%), spindle (38.1%), and epithelioid (9.5%) myoepithelial cells were observed. Oncocytic (47.6%) and mucous (19%) cells were also found. The stroma was predominantly fibrous (95.2%), followed by myxoid (66.7%), hyaline (61.9%), and chondromyxoid (33.3%). Squamous (57.1%), adipose (47.6%), sebaceous (14.3%), and bone (14.3%) differentiations were found. Additionally, a group of tumors presented pleomorphism (23.8%), mitoses (14.3%), capsule infiltration (9.5%), and necrosis. The presence of cystic structures occurred significantly in patients older than 30 years (P = .04) and mitoses were more observed in PA from buccal mucosa (P = .026). All cases that presented plasmacytoid cells were smaller than 1.5 cm (P = .015). All tumors with up to 50% stroma area presented with size smaller than 2.0 cm (P = .013). Intraoral PA presents a large morphological spectrum and several microscopic features are associated with clinical findings.