Immunohistochemical Findings in Retrocorneal Membranes of Eyes with Corneal Decompensation after Complicated Intraocular Surgery.

BACKGROUND: Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. METHODS AND PATIENTS: Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. RESULTS: On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. CONCLUSIONS: In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium.

Liver damage and senescence increases in patients developing hepatocellular carcinoma.

BACKGROUND AND AIM: Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes a continuous damage leading to liver cirrhosis and eventually HCC. However, only a minority of cirrhotic patients develop HCC. To assess a possible differential impact of liver inflammation in patients developing HCC versus patients remaining tumor-free, we designed a longitudinal study and analysed liver tissue of the same patients (n = 33) at two points in time: once when no HCC was present and once several years later when an HCC was present. As a control group, we followed cirrhotic patients (n = 37) remaining tumor-free over a similar time frame. METHODS: We analysed cell damage and senescence of hepatocytes by measuring γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, nuclear size, and telomere length. RESULTS: γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, in the first liver biopsy was similar in patients developing HCC later on and cirrhotic patients remaining tumor free. In contrast, γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, was significantly higher in the second non-tumoral liver biopsy of HCC patients than in the control patients. Consequently, the individual increase in γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, from the first biopsy to the second biopsy was significantly higher in patients developing HCC than in patients remaining tumor free. In addition, changes in nuclear size and telomere length revealed a more pronounced cell aging in patients developing HCC than in patients remaining tumor free. CONCLUSIONS: Hepatocytes from patients developing HCC go through more pronounced cell damage and senescence in contrast to cirrhotic patients remaining tumor free.

Clinicopathological Features and Metastatic Pattern of Hepatocellular Carcinoma: An Autopsy Study of 398 Patients.

OBJECTIVES: Analysis of a large local autopsy collective to gather epidemiological and histopathological data on hepatocellular carcinoma (HCC). METHODS: We examined a large dataset of 44,104 autopsies performed at the Institute of Pathology, Basel, Switzerland, including 2 autopsy collectives (1969-1983 and 1988-2012) to gather current data on HCC in the advanced stage. A total of 398 HCC were diagnosed, accounting for around 1% of all autopsies. RESULTS: As expected, most patients developing HCC had advanced stages of liver fibrosis or cirrhosis (F3/F4). However, in the more recent autopsy collective (1988-2012), our data also show an increase of HCC arising in livers without or with only mild to moderate fibrosis (F0-F2). Extrahepatic metastasis was found in 156 of 398 HCC (39.1%), with lung metastasis (74.5%) being the most common, followed by the bones (24.8%) and adrenal glands (19.1%). CONCLUSIONS: Our data therefore seem to suggest that, in the last 2 decades, despite the introduction of new therapeutic modalities for HCC, no significant changes have been observed regarding the metastatic pattern of advanced HCC.

Why a standard contrast-enhanced MRI might be useful in intracranial internal carotid artery stenosis.

In patients with ischemic stroke of unknown cause cerebral vasculitis is a rare but relevant differential diagnosis, especially when signs of intracranial artery stenosis are found and laboratory findings show systemic inflammation. In such cases, high-resolution T1w vessel wall magnetic resonance imaging (MRI; 'black blood' technique) at 3 T is preferentially performed, but may not be available in every hospital. We report a case of an 84-year-old man with right hemispheric transient ischemic attack and signs of distal occlusion in the right internal carotid artery (ICA) in duplex sonography. Standard MRI with contrast agent pointed the way to the correct diagnosis since it showed an intramural contrast uptake in the right ICA and both vertebral arteries. Temporal artery biopsy confirmed the suspected diagnosis of a giant cell arteritis and dedicated vessel wall MRI performed later supported the suspected intracranial large artery inflammation. Our case also shows that early diagnosis and immunosuppressive therapy may not always prevent disease progression, as our patient suffered several infarcts in the left middle cerebral artery (MCA) territory with consecutive high-grade hemiparesis of the right side within the following four months.

Histopathology of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

An unexpected cause of diffuse alveolar hemorrhage in a kidney transplant patient.

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring urgent treatment. There are many different treatment-relevant causes of DAH, making the diagnostic approach to these patients complex and necessitating a multidisciplinary team. We report the case of a kidney transplant recipient in whom all diagnostic efforts did not reveal the cause of DAH, and only autopsy was able to establish an unexpected diagnosis.

Identification of New Players in Hepatocarcinogenesis: Limits and Opportunities of Using Tissue Microarray (TMA).

Liver tumours are among the leading causes of cancer-related death worldwide and hepatocellular carcinoma (HCC) accounts for the vast majority of liver tumours. When detected at an early stage of disease, patients might still be eligible for surgical-based curative treatments. However, currently only small portion of HCC affected patients are diagnosed at an early stage. For late stage HCC no treatment option exists beside the multi-tyrosine kinase inhibitor Sorafenib. Thus new molecular targets and treatment options for HCC are urgently needed. Nevertheless, despite some improvements in diagnosis and patient management, the biology of liver tumour remains inadequately understood, mainly because these tumours have shown to harbour a highly complex genomic landscape. In addition, one major obstacle delaying the identification of new molecular targets in biomedical research is the necessity to validate them using a large collection of tissue specimens. Tissue microarray (TMA) technology allows the prompt molecular profiling of multiple tissue specimens and is therefore ideal to analyze presumptive candidate biomarkers in a fast an effective manner. The use of TMA has substantial benefits over standard techniques and represents a significant advancement in molecular pathology. For example, TMA technology reduces laboratory work, offers a high level of experimental uniformity and provides a judicious use of precious tissue. On the other hand, one potential limitation of using TMA is that the small cores sampled may not be representative of whole tumors. This issue is very critical in particularly heterogeneous cancers such as HCC. For liver focused studies, it is ideal to evaluate the staining patters of a determined marker over the structure of an entire acinus and to define staining in as many as possible anatomical regions. In this review we analyze the limits and opportunities offered by the usage of TMA technology in HCC research. In summary, TMA has revolutionized the histopathological analysis and will be of great help to further advance the knowledge in the field of hepatocarcinogenesis research.

Topical nasal steroid treatment does not improve CPAP compliance in unselected patients with OSAS.

BACKGROUND: Continuous positive airways pressure (CPAP) for treatment of obstructive sleep apnea (OSA) can produce troublesome nasal symptoms (i.e. congestion, rhinorrhea) that may reduce the compliance of CPAP. Topical nasal steroids are often prescribed to reduce these side effects, although scientific data are scarce supporting any benefits of this treatment for CPAP-induced nasal side effects. OBJECTIVE: To study whether a topical nasal steroid can reduce CPAP-induced nasal symptoms and improve CPAP adherence during the initial phase of OSA treatment. METHODS: A randomized, double-blinded, placebo-controlled study with fluticasone propionate 100 µg/nasal cavity twice daily Treatment was started 10 days prior to and continued throughout the first 4 weeks of CPAP. 63 patients who were selected for CPAP treatment participated. Nasal symptoms were recorded, nasal patency was assessed and lung function was measured with a peak flow meter. The patients' adherence to CPAP was recorded by the CPAP device. RESULTS: Total nasal symptoms increased from baseline to 4 wks after CPAP use for both nasal treatments (p < 0.05). No differences in total nasal symptoms between treatments were seen (p = 1), and no differences in nasal peak flow values after treatment were seen (p = 0.11). Moreover, there were no differences in CPAP use between the treatments. CONCLUSION: Fluticasone propionate as a nasal topical steroid does not reduce CPAP-induced unwanted nasal side effects, and has no beneficial effect on CPAP compliance during the first four weeks of treatment in unselected patients with OSAS.