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Fulltext Exploring the molecular pathogenesis, diagnosis and treatment of fibrolamellar hepatocellular carcinoma: A state of art review of the current literature

Alshareefy Y, Shen CY, Prekash RJ

Pathol Res Pract, 2023 Aug;248:154655.
PMID: 37429175 DOI: 10.1016/j.prp.2023.154655

This paper aims to present a detailed overview of fibrolamellar carcinoma (FLC), a variant of hepatocellular carcinoma (HCC) that accounts for approximately 1-9% of all cases a. according to the SEER database. Despite ongoing research, the aetiology of FLC tumours remains unclear. Nevertheless, FLC is believed to have a better overall prognosis than other primary liver tumours, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. This study aims to present a comprehensive overview of fibrolamellar carcinoma (FLC), with a focus on its epidemiology, pathogenesis, diagnosis, treatment, and prognosis. FLC frequently incorporate features of stomach pain, weight loss, and malaise in their clinical signs and symptoms, which are generally nonspecific Ultimately, the most common physical finding is an abdominal mass or hepatomegaly. With this said, several unusual presentations have been documented such as Budd Chiari syndrome, severe anaemia, non-bacterial thrombotic endocarditis and many more. In regards to this tumour's genetic analysis, it is characterised by a 400 kb deletion on chromosome 19 leading to a functional DNAJB1-PRKACA chimeric transcript in addition to tetraploidy in 50% of cases. FLC is chromosomally stable as compared to typical HCC. mTOR pathway activation has also been found to play a critical role in 47% of these tumours and EFGR over-expression is also evident. Fibrolamellar carcinomas (FLCs) exhibit a distinctive gross appearance, characterized by a yellow to pale tan colour, with a consistency that can vary from soft to firm and hard. In addition, a central scar is observed in 60-70% of FLC cases. The central scar is typically white or grey in colour and has a fibrous appearance, which is often surrounded by nodular, tumour-like tissue. Its histologic appearance is characterized by large polygonal cells with abundant eosinophilic cytoplasm, large vesiculated nuclei, large nucleoli, and arranged in lamellar bands of collagen fibres. Lamellar bands of fibrosis, consisting of collagen type I, III and IV, have also been identified as a distinctive histologic feature that is observed under low power magnification. Ultrasound, CT and MRI along with image guided biopsy are the primary modalities in diagnosis. Current management options include systemic therapy which has thus far been unremarkable with platinum-based therapies as well combination therapy with interferon alpha-2b being the most successful options. Surgical resection remains the primary treatment modality and there have been no advances in targeted therapies. Although the prognosis for FLC is favourable as compared to other hepatic cancer subtypes such as intrahepatic cholangiocarcinoma, there is a high rate of recurrence ranging from 33% to 100% with a median recurrence-free survival of 20-48 months. As a result of this there is a low overall cure rate associated with this tumour type and much more research is required to gain an in-depth understanding of the molecular mechanisms occurring in order to provide more adequate treatment to patients who suffer from this condition.

Matched MeSH terms: Cicatrix/pathology
Fulltext Imaging of skin birefringence for human scar assessment using polarization-sensitive optical coherence tomography aided by vascular masking

Gong P, Chin L, Es'haghian S, Liew YM, Wood FM, Sampson DD, et al.

J Biomed Opt, 2014 Dec;19(12):126014.
PMID: 25539060 DOI: 10.1117/1.JBO.19.12.126014

We demonstrate the in vivo assessment of human scars by parametric imaging of birefringence using polarization-sensitive optical coherence tomography (PS-OCT). Such in vivo assessment is subject to artifacts in the detected birefringence caused by scattering from blood vessels. To reduce these artifacts, we preprocessed the PS-OCT data using a vascular masking technique. The birefringence of the remaining tissue regions was then automatically quantified. Results from the scars and contralateral or adjacent normal skin of 13 patients show a correspondence of birefringence with scar type: the ratio of birefringence of hypertrophic scars to corresponding normal skin is 2.2 ± 0.2 (mean ± standard deviation ), while the ratio of birefringence of normotrophic scars to normal skin is 1.1 ± 0.4 . This method represents a new clinically applicable means for objective, quantitative human scar assessment.

Matched MeSH terms: Cicatrix/pathology*
Securing the airway in a child with extensive post-burn contracture of the neck: a novel strategy

Wong TE, Lim LH, Tan WJ, Khoo TH

Burns, 2010 Aug;36(5):e78-81.
PMID: 20036061 DOI: 10.1016/j.burns.2009.10.016
Matched MeSH terms: Cicatrix/pathology
A viable secondary intra-abdominal pregnancy resulting from rupture of uterine scar: role of MRI

Teng HC, Kumar G, Ramli NM

Br J Radiol, 2007 Jul;80(955):e134-6.
PMID: 17704308

Pre-natal diagnosis of intra-abdominal pregnancy is difficult. Ultrasound has been the frontline modality to date; however, it gives a diagnostic error of 50-90% and its use is disappointing. In recent years, MRI has emerged as an appealing imaging modality. With its good soft tissue contrast and non-ionizing property, it acts as a means of definitive non-invasive assessment before surgical intervention when ultrasound is inconclusive.

Matched MeSH terms: Cicatrix/pathology
Effect of bis [benzyl N'-(indol-3-ylmethylene)-hydrazinecarbodithioato]-zinc(II) derivatives on wound healing in Sprague Dawley rats

Mughrabi FF, Hashim H, Ameen M, Khaledi H, Ali HM, Ismail S

Indian J Exp Biol, 2011 Jan;49(1):50-5.
PMID: 21365996

Effects of topical application of Bis[benzyl N'-(indol-3-ylmethylene)-hydrazinecarbodithioato]-zinc(II) (BHCZ) on wound healing and histology of healed wound were assessed. Sprague Dawley rats were experimentally induced wound in the posterior neck area. Tween 20 (0.2 ml of 10%) was applied to rats in Group 1 (negative control). Intrasite gel (0.2 ml) was applied topically to rats in Group 2 as reference. BHCZ at the concentrations 0.2 ml of 25, 50 and 100 mg/ml were applied to Group 3, 4 and 5, respectively. Wound dressed with BHCZ significantly healed earlier than those treated with 10% Tween 20. Also wound dressed with 100 mg/ml BHCZ accelerated the rate of wound healing compared to those dressed with intrasite gel and, 25 mg/ml and 50 mg/ml BHCZ. Histological analysis of healed wound with BHCZ showed comparatively less scar width at wound enclosure and the healed wound contained less macrophages and large amount of collagen with angiogenesis compared to wounds dressed with 10% Tween 20. Results of this study showed that wounds dressed with 100 mg/ml of BHCZ significantly enhanced acceleration of the rate of wound healing enclosure, and histology of healed wounds showed comparatively less macrophages and more collagen with angiogenesis.

Matched MeSH terms: Cicatrix/pathology
Dried irradiated human amniotic membrane as a biological dressing for facial burns--a 7-year case series

Bujang-Safawi E, Halim AS, Khoo TL, Dorai AA

Burns, 2010 Sep;36(6):876-82.
PMID: 20236771 DOI: 10.1016/j.burns.2009.07.001

Facial burns are common and have a significant impact on patient function and psychosocial well being. Human amnion has been used for many years as a temporary biological wound dressing in the management of partial thickness burns. The observed advantages of human amnion treatment include pain relief, ease of use, prevention of infection and acceleration of wound healing.

Matched MeSH terms: Cicatrix/pathology
Sutureless skin closure for cleft lip repair

Mourougayan V

Cleft Palate Craniofac J, 2006 Nov;43(6):656-8.
PMID: 17105330

To study the quality of scars following the use of butyl cyanoacrylate to close the skin during cleft lip repair.

Matched MeSH terms: Cicatrix/pathology
Salzmann's nodular degeneration of the cornea

Vannas A, Hogan MJ, Wood I

Am J Ophthalmol, 1975 Feb;79(2):211-9.
PMID: 46719

Eleven corneal specimens from nine patients with Salzmann's nodular degeneration of the cornea, together with all available clinical information, were collected for this study. The specimens were examined by light and electron microscopy. An antecedent keratitis was diagnosed by history and microscopic findings in every case. The corneal epithelium showed degenerative changes, its thickness varied, and in nodular areas it often consisted of only a single layer of flattened epithelial cells by light microscopy. Bowman's membrane was missing over the nodules, and in this zone there was excessive secretion of a basement membrane-like material. Hyaline degeneration of collagen, cellular debris, and electron-dense hyaline deposits were seen in the collagen of the nodules. The number of fibrocytes in the nodules varied from many that were active to a few that were degenerating. External irritation because of poor epithelial protection was interpreted as a causative factor, although other tissue repair mechanisms may also have played a role.

Matched MeSH terms: Cicatrix/pathology
Superior long term functional and scar outcome of Meek micrografting compared to conventional split thickness skin grafting in the management of burns

Lee SZ, Halim AS

Burns, 2019 09;45(6):1386-1400.
PMID: 31054957 DOI: 10.1016/j.burns.2019.04.011

INTRODUCTION: Autologous skin grafting is the mainstay of treatment in burn patients. Extensive full thickness burns remains a challenge to the burns surgeon due to the lack of autologous skin donor sites. The conventional split thickness skin grafting (SSG) and the Meek micrografting (Meek) technique are part of the armamentarium of the burns surgeon to curtail the challenge of paucity of donor sites. With advances in burn care, mortality rates of burn patients have reduced. As a result, with more patients surviving acute burn, there is a paradigm shift of research towards assessment of functional outcomes and quality of life of the burn survivors. As there is lack of research regarding the functional outcome of the Meek technique, this study was designed to examine the long term functional outcome of the Meek technique and SSG in burns.
METHOD: A cross-sectional study was conducted in Hospital Universiti Sains Malaysia to assess patients with burns between 10 to 40% total body surface area (TBSA) and with at least one year after injury. The Burn Specific Health Score-brief (BSHS-B) was utilized to compare the functional outcome whilst the Vancouver Scar Scale (VSS) was used for comparison on the scar outcome of the two skin grafting techniques.
RESULTS: Forty three patients (Meek,15; SSG,28) were included. The mean current age (years old) of Meek and SSG was 24.7 (range, 7-75) and 25.9 (range, 7-65) respectively. The mean TBSA (%) of the Meek group was 26.7 (range, 13-40) while that of the SSG group was 16.1 (range, 10-32). A simplified domain structure was used for the BSHS-B questionnaire. The work and sexuality subscale were analyzed separately due to missing data. There mean scores of affect and relations was higher in Meek compared to SSG (Meek, 3.86; SSG, 3.75; p > 0.05). Function domain was also better in Meek compared to SSG (Meek, 3.88; SSG, 3.73; p > 0.05). The Meek group displayed superior scar outcome compared to SSG as evidenced by the statistically significant difference in score for the pigmentation, pliability, height and total VSS score.
CONCLUSION: The Meek group showed more favorable BSHS-B scores compared to the SSG group. The scar outcome of the Meek technique is significantly superior to SSG. Therefore, the Meek technique is superior in the management of burns because the long term scar and functional outcome of this technique is better compared to conventional SSG.

Matched MeSH terms: Cicatrix/pathology
Donor-site morbidity of free fibula and DCIA flaps

Ling XF, Peng X, Samman N

J Oral Maxillofac Surg, 2013 Sep;71(9):1604-12.
PMID: 23810616 DOI: 10.1016/j.joms.2013.03.006

This study evaluated and compared the long-term donor-site morbidity of the free fibula flap with the deep circumflex iliac artery (DCIA) flap in maxillofacial reconstruction.

Matched MeSH terms: Cicatrix/pathology
Effects of ranibizumab on TGF-β1 and TGF-β2 production by human Tenon's fibroblasts: An in vitro study

Noh SM, Abdul Kadir SH, Crowston JG, Subrayan V, Vasudevan S

Mol Vis, 2015;21:1191-200.
PMID: 26539031

Inhibiting exaggerated wound healing responses, which are primarily mediated by human Tenon's fibroblast (HTF) migration and proliferation, has become the major determining factor for a successful trabeculectomy. Antivascular endothelial growth factor (anti-VEGF) has showed promising results as a potential antifibrotic candidate for use concurrently in trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. However, the effects on HTFs remain unclear. This study was conducted to understand the effects of ranibizumab on transforming growth factor (TGF)-β1 and transforming growth factor (TGF)-β2 expression by HTFs.

Matched MeSH terms: Cicatrix/pathology