Unexplained visual loss after primary pars-plana-vitrectomy with silicone oil tamponade in fovea-sparing retinal detachment.

BACKGROUND: To investigate the incidence and clinical characteristics of unexplained visual loss in patients with fovea-sparing rhegmatogenous retinal detachment (RRD) during or after silicone oil (SO) tamponade. METHODS: The medical charts of all patients with macula-on RRDs, who underwent pars-plana-vitrectomy (ppV) with SO tamponade were retrospectively assessed regarding unexplained visual loss (UVL) of ≥ 3 Snellen lines and alterations on optical coherence tomography (OCT) during or after SO tamponade. The clinical data analysed included visual acuity, surgical parameters, OCT images, duration of SO tamponade and the time point of visual decline. Cases with re-detachment or secondary causes of visual loss such as SO emulsification, epiretinal membranes or macular edema were excluded. RESULTS: Over a 15-year-period, 22 cases with macula-on RRD, which had primarily been treated with ppV and SO tamponade, met the inclusion criteria. In most eyes (n = 20; 91%), the RRD was caused by a giant retinal tear (GRT). In 11 of these 22 cases (50%), best-corrected visual acuity (BCVA) had dropped by at least 3 lines for no apparent reason. In these 11 cases, mean preoperative logMAR BCVA was 0.2 (SD 0.13; range 0-0.5), equal to Snellen's VA of 0.63, and mean postoperative logMAR BCVA 1.0 (SD 0.24; range 0.5-1.3), equal to Snellen's VA of 0.10. Visual decline occurred about 12 weeks postoperatively (SD 6.2; range 3-20 ) and comprised 8 lines (SD 2.3; range -11 to -4). SO was removed on average 139 (SD 50.0; range 88-271) days after the first ppV. In 9 cases visual decline occurred while the SO was in-situ. In 2 patients, BCVA decline was noted 2 weeks after SO removal. In all eyes, preoperative central foveal thickness (CFT) was 254 µm (SD 24.2), which decreased to 224 µm (SD 29.6) during SO tamponade and increased to 247 µm (SD 29.2) after SO removal, irrespective of the presence of UVL. The mean follow-up time was 20 months (SD 30.6) after SO removal. CONCLUSION: UVL after SO tamponade for macula-on RRD is more frequent than expected. The incidence in our case series was 50%. The mechanism of this phenomenon is still unknown. In general, vitreoretinal surgeons should thoroughly question the need for SO tamponade, inform their patients of possible UVL and remove SO as early as possible. TRIAL REGISTRATION: The study was approved by the local ethics committee on 6th of May 2022 (Ethikkommission der Universität Regensburg, Votum 22-2925-104) and was conducted in accordance with the ethical standards of the Declaration of Helsinki.

[Primary extra-axial chondroid chordoma of the anterior nasal septum: case report of a rare chordoma with literature review]. / Primäres extraaxiales chondroides Chordom des anterioren Nasenseptums: Fallbericht eines seltenen Chordoms mit Literaturübersicht.

An 87-year-old patient reported a nodular, progressively enlarging mass of the anterior nasal septum leading to partial obstruction of the nostrils. The tumor showed no infiltration of the subcutis, bone, or paranasal sinuses in imaging or intraoperatively. Histological examination revealed a chondroid tumor with lobular growth and physaliferous cell morphology. Immunohistochemistry revealed a brachyury-positive tumor without EWSR1 rearrangement, leading to the diagnosis of a chondroid chordoma. The reported case demonstrates the differential diagnostic considerations pertaining to this rare tumor, which can also have an untypical and very rare extra-axial location. Review of the literature identified 34 primary extraosseous chordomas of the nose, nasopharynx, and paranasal sinuses, and allowed the nasal chordoma presented herein to be included in this group of extra-axial chordomas.

S-Nitrosothiol Signaling Is involved in Regulating Hydrogen Peroxide Metabolism of Zinc-Stressed Arabidopsis.

Accumulation of heavy metals such as zinc (Zn) disturbs the metabolism of reactive oxygen (e.g. hydrogen peroxide, H2O2) and nitrogen species (e.g. nitric oxide, NO; S-nitrosoglutathione, GSNO) in plant cells; however, their signal interactions are not well understood. Therefore, this study examines the interplay between H2O2 metabolism and GSNO signaling in Arabidopsis. Comparing the Zn tolerance of the wild type (WT), GSNO reductase (GSNOR) overexpressor 35S::FLAG-GSNOR1 and GSNOR-deficient gsnor1-3, we observed relative Zn tolerance of gsnor1-3, which was not accompanied by altered Zn accumulation capacity. Moreover, in gsnor1-3 plants Zn did not induce NO/S-nitrosothiol (SNO) signaling, possibly due to the enhanced activity of NADPH-dependent thioredoxin reductase. In WT and 35S::FLAG-GSNOR1, GSNOR was inactivated by Zn, and Zn-induced H2O2 is directly involved in the GSNOR activity loss. In WT seedlings, Zn resulted in a slight intensification of protein nitration detected by Western blot and protein S-nitrosation observed by resin-assisted capture of SNO proteins (RSNO-RAC). LC-MS/MS analyses indicate that Zn induces the S-nitrosation of ascorbate peroxidase 1. Our data collectively show that Zn-induced H2O2 may influence its own level, which involves GSNOR inactivation-triggered SNO signaling. These data provide new evidence for the interplay between H2O2 and SNO signaling in Arabidopsis plants affected by metal stress.

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to traumatic choroidal rupture.

BACKGROUND: So far only single cases with short follow-up have been reported on the use of intravitreal anti-VEGF for traumatic choroidal neovascularizations (CNV). This paper reports a large case series of patients with CNV secondary to choroidal rupture after ocular trauma receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: Fifty-four patients with unilateral choroidal rupture after ocular trauma diagnosed between 2000 and 2016 were retrospectively evaluated. Eleven patients with CNV secondary to choroidal rupture were identified. Five eyes with traumatic secondary CNV were treated with anti-VEGF and were systematically analysed. The other 4 patients with inactive CNV underwent watchful observation. RESULTS: Four men and one woman with a mean age of 29 years (SD 12.4; range 19-45) had intravitreal anti-VEGF therapy for traumatic CNV. Another 4 patients with a mean age of 37 years (SD 6.6; range 31-46) presented with inactive CNV and did not receive specific treatment. In all 9 cases the mean interval between the ocular trauma and the diagnosis of CNV was 5.7 months (SD 4.75; range 2-12). In the treatment group per eye 4.2 injections (SD 3.2; range 1-8) were given on average. Four eyes were treated with bevacizumab and one eye with ranibizumab. Regression of CNV was noted in all eyes. In 4 eyes visual acuity (VA) improved, one eye kept stable visual acuity. CONCLUSIONS: Here, we present the up to now largest case series of traumatic CNV membranes treated with anti-VEGF injections with a mean follow-up period of 5 years. Intravitreal anti-VEGF therapy seems to be safe and effective for secondary CNV after choroidal rupture. Compared to exudative age-related macular degeneration fewer injections are needed to control the disease. TRIAL REGISTRATION: Retrospective registration with local ethics committee on 21 March 2019. Trial registration number is 19-1368-104.

U-CH17P, -M and -S, a new cell culture system for tumor diversity and progression in chordoma.

Chordoma is a rare bone tumor with a known intrinsic heterogeneity. Here, we address this tumor heterogeneity in a new cell culture model for tumor diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumor tissues revealed that the precursor cells of U-CH17P, U-CH17M and U-CH17S were already present in the primary tumor. Therefore, we show that clonal diversity of this chordoma exists in the primary tumor and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumor progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology.

[New aspects on giant cell tumor of bone]. / Neue Aspekte zum Riesenzelltumor des Knochens.

A giant cell tumor of bone (GCTB) is one of the giant cell-rich lesions of bone and has to be differentiated from non-ossifying fibroma, aneurysmatic bone cyst, chondroblastoma, "brown tumor" and osteosarcoma containing giant cells. A hallmark of GCTB is the presence of the distinct histone 3 (H3F3A) mutation G34W and its detection either by sequencing methods or using immunohistochemistry with a novel antibody against this mutational site. Worrisome is the fact that under denosumab therapy a histological change of the lesions can be seen and there are first reports of sarcomas arising after therapy. When diagnosing giant cell-rich lesions, pathologists should be aware of the various differential diagnoses and morphological spectrum within GCTB.

[Presacral lesion at the rima ani]. / Präsakrale Raumforderung an der Rima ani.

A 26-year-old woman presented with a painful bulge at the rima ani. The tumor was located in the presacral region. Histological examination revealed a well-circumscribed biphenotypical tumor with papillary configured myxoid areas and strongly sclerosing regions. This case of a myxopapillary ependymoma is a rare example of a myxoid neoplastic lesion in the sacral region.

[Notochordal tumors : Benign notochordal tumors and chordomas]. / Notochordale Tumoren : Benigne notochordale Tumoren und Chordome.

Benign notochordal tumors (BNCT) and chordomas are primary bone tumors of the spine with a predominant localization in the sacrum and clival region followed by the vertebral bodies. Besides the most common variant (NOS [not otherwise specified] with hepatoid or renal carcinoma cell-like differentiation) chordomas with chondroid, and polymorphic to anaplastic morphology are described. An unfavorable variant are pediatric chordomas with a loss of INI-1. BNCT and chordomas are characterized by the following immunohistological profile: vimentin+, cytokeratin+/-, epithelial membrane antigen (EMA)+/-, S100 protein+/-, brachyury+. This profile helps to distinguish these tumors from other lesions such as chondrosarcoma, chordoid meningioma, and metastases of carcinoma.

[H3F3A mutated multicentric giant cell tumor of bone : A very rare primary bone disease]. / H3F3A-mutierter multifokaler Riesenzelltumor des Knochens : Eine äußerst seltene primär ossäre Erkrankung.

This article presents the case of a metachronic multicentric giant cell tumor of bone (GCTB). The patient obtained his first diagnosis of GCTB in the left humerus at the age of 47 years. Furthermore, he suffered from a GCTB in the head of his 4th left metacarpal bone and from a recurrence of the latter. All tumors carried the characteristic H3F3A mutation, which was proven by Sanger sequencing and a mutation specific antibody. The case is the first description of a multicentric H3F3A mutated GCTB.

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to punctate inner choroidopathy.

PURPOSE: To assess the outcome of patients with choroidal neovascularization (CNV) secondary to punctate inner choroidopathy (PIC) receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: Sixteen eyes of 16 patients diagnosed with CNV secondary to PIC were retrospectively assessed. RESULTS: Eleven women and five men with a mean age of 35 years (SD 11, range 16-56 years) received intravitreal anti-VEGF for PIC-related CNV. On average, 3.5 injections (SD 2.7, range 1-9) were given per eye. Thirteen eyes were treated with bevacizumab, two eyes with ranibizumab and one eye received both substances. The mean follow-up was 15 months (SD 11, range 6-40 months). BCVA improved in eight eyes (mean Δ +2.8 lines), remained stable in four eyes and decreased in four eyes (mean Δ -4.3 lines). CONCLUSIONS: CNV development is a frequent complication of PIC. Intravitreal anti-VEGF therapy seems to be safe and effective for PIC-related CNV.

Taking the next step forward - Diagnosing inherited infantile cholestatic disorders with next generation sequencing.

Identifying rare genetic forms of infantile cholestasis is challenging due to their similar clinical presentation and their diverse etiology. After exclusion of common non-genetic causes a huge list of rare differential diagnosis remains to be solved. More than 90 genes are associated with monogenic forms of infantile cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we demonstrate a next generation sequencing approach to discover the underlying cause in clinically well characterized patients in whom common causes of infantile cholestasis have been excluded. After validation of the analytical sensitivity massive parallel sequencing was performed for 93 genes in six prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) and two known pathogenic mutations were detected proving our multi gene panel for infantile cholestasis to be a sensitive and specific method overcoming the complexity of the phenotype-based, candidate gene approach. Three exemplary clinical cases of infants with cholestasis are presented and discussed in the context of their genetic and histopathological findings (autosomal recessive polycystic kidney disease, atypical PFIC and Niemann-Pick syndrome type C1). These case reports highlight the critical impact of integrating clinical, histopathological and genetic data during the process of multi gene panel testing to ultimately pinpoint rare genetic diagnoses.

Malignant extrarenal rhabdoid tumour (MERT) with liver metastases as a rare cause of an esophageal tumor in a 57 years old patient.

Tumors with a rhabdoid phenotype are aggressive neoplasms with a dismal prognosis. Malignant extrarenal rhabdoid tumor (MERT) of the esophagus is an extremely rare disease with so far only 6 cases reported. We report on a 57-year-old male patient with rhabdoid tumor situated in the esophagus with metastases to the liver and local lymph nodes. Assuming an undifferentiated esophageal adenocarcinoma a palliative chemotherapy with 5-FU/folinic acid, oxaliplatin, and docetaxel (FLOT) was initiated which was changed towards a combination of doxorubicin and ifosphamide as immunohistochemistry of the primary and the liver metastases revealed a rhabdoid tumor. This treatment with doxorubicin and ifosphamide resulted in a short clinical and radiological response which lasted only for 2 months. Due to the bad general condition at the time of progression no further chemotherapy was initiated. The patient died due to tumor progression 6 months after initial diagnosis which is consistent with other reports on malignant extrarenal rhabdoid tumors (median survival of metastatic disease less than 6 months). Thus, metastatic MERT represents a disease with a poor prognosis and no established standard therapy.

[Detection of the BCR-ABL fusion: Comparative analysis of six commercially available FISH fusion probes]. / Detektion der BCR-ABL-Fusion : Vergleichende Analyse sechs kommerzieller FISH-Sondensätze.

Chronic myeloid leukemia (CML) is diagnostically defined by the reciprocal translocation t(9;22)(q34;q11). This aberration can be detected by the BCR-ABL fluorescence in situ hybridization (FISH) technique. This article presents a comparative analysis of different commercially available FISH probes and different FISH protocols in order to optimize this technique on formalin-fixed and paraffin-embedded bone marrow trephine biopsies.

[Manifestation of rheumatic diseases in the larynx]. / Erkrankungen des rheumatischen Formenkreis mit Manifestation im Larynx.

Rheumatic disorders (rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis) may affect the larynx. The clinical symptoms are often unspecific, leading to delayed diagnosis. Malignant tumours should be considered in differential diagnosis with necessitating biopsy. Treatment may require interdisciplinary approach together with a specialist in internal medicine and rheumatology.

[Cystic echinococcosis and hepatocellular carcinoma--a coincidence? A case report]. / Zystische Echinokokkose und hepatozelluläres Karzinom--zufällige Koinzidenz? Ein Fallbericht.

INTRODUCTION: The coincidence of echinococcosis and hepatocellular carcinoma (HCC) is quite rare. We report the case of a 45-year-old man who was admitted to our hospital because of abdominal pain in the right upper quadrant and jaundice. Clinical features and diagnostics: There was no history of weight loss or fever. No abdominal mass was palpable. The laboratory reports showed increased transaminase levels. Ultrasonography revealed an inhomogenous, cystic lesion measuring 6 cm in diameter in the segments VI and VII. Serology for echinococcosis was negative, alpha-fetoprotein (AFP) was considerably increased. CT scan showed a solid mass of 3,7 cm in diameter adjacent to the cystic lesion. THERAPY AND COURSE: Anthelminthic therapy with albendazole caused a massive increase of cholestasis parameters and treatment had to be stopped. The simultaneous occurrence of serologically negative cystic echinococcosis and HCC was suspected and partial liver resection was performed. Histological examination confirmed both diagnoses and tumor resection in healthy tissue. 5 months after resection CT scan showed multicentric HCC affecting the whole liver. Palliative therapy with sorafenib was established. DISCUSSION: The coincidence of HCC and cystic echinococcosis in the non-cirrhotic liver of a young man is a rare event. Despite resection in healthy tissue multicentric HCC was diagnosed 5 months later. Only few cases of simultaneous occurrence of HCC and echinococcosis have been published so far. Some authors considered echinococcosis as a trigger for HCC. A causal link between both entities has not been demonstrated until now.

[Outcome and complications after trabeculectomy depending on the preoperative intraocular pressure]. / Sechs-Monats-Verlauf nach Trabekulektomie in Abhängigkeit vom Ausgangsdruck.

PURPOSE: Trabeculectomy is a frequently used surgical procedure in open-angle glaucomas. The present study analyses the outcome and complications after trabeculectomy or re-trabeculectomy depending on the preoperative intraocular pressure (IOP) < 30 mmHg and ≥ 30 mmHg. METHODS: One hundred and eighteen patients were included in this retrospective study. Primary ocular outcomes were the postoperative IOP at discharge and postoperative complications such as choroidal detachment and flattening of the anterior chamber. The necessity of postoperative interventions such as needle revisions, viscoelastic injections or surgical revision was documented. RESULTS: In this survey 118 patients (68 men, 50 women) were included (age [arithmetic mean] 68.3 ± 12.1 years). The postoperative follow-up period was 6-9 months. In 60 patients the preoperative IOP was < 30 mmHg, in 58 patients ≥ 30 mmHg. Postoperative complications were flattening of the anterior chamber (< 2 corneal thickness) in 11 patients (9.3 %) and temporary choroidal detachment in 20 patients (16.9 %). On the day of discharge the mean IOP was 9.8 mmHg. Hence the IOP was on average reduced by 17 mmHg (SD 11.2 mmHg). Postoperative interventions were necessary in 28 patients (23.7 %). Seventeen (14.4 %) developed tenon cysts which were treated by needle revision of the bleb. Nine patients (7.6 %) underwent a viscoelastic injection for persistent hypotony and 10 patients underwent bleb revision (8.5 %). CONCLUSIONS: This study does not show statistically significant differences depending on preoperative IOP in temporary choroidal detachment and postoperative interventions. A postoperative flattening of the anterior chamber was found statistically significantly more often in patients with higher preoperative IOP.

Comparability of input parameters in the German Retina.net ROP registry and the EU-ROP registry - An exemplary comparison between 2011 and 2021.

PURPOSE: The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries. METHODS: Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments. RESULTS: The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021. CONCLUSION: Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021.

[Gastric lymphoma: still an interdisciplinary challenge]. / Das Lymphom im Magen: Eine persistierende interdisziplinäre Herausforderung.

Differentiation of chronic gastritis from marginal zone B-cell lymphoma (MZoL) of MALT type is often difficult for the pathologist. Diagnostic tools include CD20 stain to highlight lymphoepithelial lesions, Wotherspoon grading of the infiltrate, and clonality analysis of the B-cells. MZoL may partially transform into a diffuse, large B-cell lymphoma, which the authors have named blastic MZoL. Blastic MZoL may be present with or without small cell MZoL. Without this component, blastic MzoL, while being CD10-negative, is presently difficult to positively diagnose since specific immune markers are still lacking. Blastic MZoL has a very favourable outcome compared to conventional diffuse large B-cell lymphomas (DLBCL). Moreover, there are conventional DLBCL in the stomach, mostly in a setting of a secondary organ involvement. The biology of these gastric DLBCL is identical to their extragastric counterparts. This is also true for primary gastric Burkitt lymphoma and mucosal involvement in B-CLL or mantle cell lymphoma. Unfavourable outcomes are always observed for EBV-triggered lymphoproliferations in immunodeficiency and peripheral T-cell lymphomas which might also arise or be initially diagnosed in the stomach.