Predictive biomarkers in gastric cancer

Predictive biomarkers are the mainstay of precision medicine. This review summarizes the advancements in tissue-based diagnostic biomarkers for gastric cancer, which is considered the leading cause of cancer-related deaths worldwide. A disease seen in the elderly, it is often diagnosed at an advanced stage, thereby limiting therapeutic options. In Western countries, neoadjuvant/perioperative (radio-)chemotherapy is administered, and adjuvant chemotherapy is administered in the East. The morpho-molecular classification of gastric cancer has opened novel avenues identifying Epstein-Barr-Virus (EBV)-positive, microsatellite instable, genomically stable and chromosomal instable gastric cancers. In chromosomal instable tumors, receptor tyrosine kinases (RKTs) (e.g., EGFR, FGFR2, HER2, and MET) are frequently overexpressed. Gastric cancers such as microsatellite instable and EBV-positive types often express immune checkpoint molecules, such as PD-L1 and VISTA. Genomically stable tumors show alterations in claudin 18.2. Next-generation sequencing is increasingly being used to search for druggable targets in advanced palliative settings. However, most tissue-based biomarkers of gastric cancer carry the risk of a sampling error due to intratumoral heterogeneity, and adequate tissue sampling is of paramount importance

Magnetic resonance imaging-based diagnosis of aortitis preceding development of a thoracic aneurysm in a patient with giant cell arteritis: a case report

Background Inflammatory manifestation in the aortic arch can be a complication of giant cell arteritis (GCA), potentially requiring surgical therapy in the case of aneurysmatic dilatation. Case summary We report the case of a 73-year-old female patient with GCA in whom a typical appearance of arteritis was visualized on magnetic resonance imaging of the superficial temporal arteries. Additionally, ectasia (4.7 cm) of the ascending aorta with a mural rim of increased contrast media uptake was detected at the time of the initial diagnosis, which is an indicator of aortitis. While the diameter had only minimally increased in a computed tomography angiography (CTA) examination after 8 months, a subsequent CTA revealed an increased diameter of 5.8 cm and maximum at the level of the ascending aorta another 22 months later, indicating urgent surgery to replace the ascending aorta. Discussion Magnetic resonance imaging can detect silent, generalized manifestations of GCA such as severe aortitis, which may possibly lead to aneurysmatic dilatation, urging closer follow-up imaging. Detection of the ongoing process and subsequent follow-up imaging protects patients by avoiding rupture

Probable cerebral amyloid angiopathy diagnosed on plain CT

Cerebral amyloid angiopathy (CAA) is the most common cause for lobar haemorrhages. The prevalence of CAA is believed to be app. 30% in non-demented elderly patients and increases with age [1]. CAA is diagnosed using the modified Boston criteria [2] which relies heavily on neuroimaging. Recently, the imaging signs “finger like projections” (FLP) and subarachnoid haemorrhage (SAH) adjacent to the main haemorrhage have been suggested as additional markers of CAA [3]. While MRI is desirable to advance the diagnosis of CAA non-invasively, in some patients, MRI is not feasible due to contraindications or logistics constraints. Moreover, plain CT remains the first-line imaging modality in the acute stage. We present a retrospectively compiled case series of patients with lobar haemorrhages in whom an MRI was not performed but many imaging features hinted towards the diagnosis of cerebral amyloid angiopathy on plain CT

A woman with a rare p.Glu74Gly transthyretin mutation presenting exclusively with a rapidly progressive neuropathy: a case report

Introduction: Familial amyloid polyneuropathy is a rare autosomal dominant disorder caused by mutations in the transthyretin gene, TTR. Diagnosis can be challenging, especially if other family members are not affected or an obvious systemic involvement is lacking. The patients are often misdiagnosed, leading to a delay in the initiation of therapy. Case presentation: A 35-year-old woman of Turkish origin presented to our outpatient clinic with severe polyneuropathy associated with distally pronounced tetraparesis and hypesthesia of 2 to 3 years’ duration. In addition, small nerve fiber involvement with impaired detection of cold temperatures and tingling pain in the lower legs was reported. She did not complain of autonomic dysfunction or visual disturbance. Her family history was empty regarding neuromuscular disorders. The routine diagnostic work-up was unremarkable. A sural nerve biopsy disclosed amyloid deposits, which led to the identification of a rare heterozygous transthyretin mutation (p.Glu74Gly; old classification: p.Glu54Gly). Conclusions: Few cases with this very heterozygous mutation can be found in the literature. In contrast to the case of our patient, all of the previously described patients in the literature presented with additional severe autonomic symptoms, involvement of the eyes and a positive family history. In this case report, we emphasize that, in patients with progressive neuropathy with small fiber involvement, an amyloid neuropathy should be considered in the differential diagnosis, even if the family history is empty and other organs are not affected

Gastric carcinomas with stromal b7-h3 expression have lower intratumoural cd8+ t cell density

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.CD8+ T cells are the main effector cells of anti-cancer immune response that can be regulated by various costimulatory and coinhibitory molecules, including members of the B7 family. B7 homolog 3 (B7-H3) appears as a promising marker for immunotherapy; however, its significance in gastric cancer (GC) is unclear yet. We evaluated the spatial distribution of CD8+ T cells in relation to the expression of B7-H3 by double immunohistochemical staining. The level of B7-H3 intensity was scored manually (0-3) and dichotomized into B7-H3-low and B7-H3-high groups. The distribution and density of CD8+ T cells was analysed using whole slide digital imaging. B7-H3 was expressed mainly in the stromal compartment of GC (n = 73, 76% of all cases). Tumours with high expression of B7-H3 showed larger spatial differences of CD8+ T cells (86.4/mm2 in tumour centre vs. 414.9/mm2 in invasive front) when compared to B7-H3-low group (157.7/mm2 vs. 218.7/mm2, respectively) (p < 0.001). This study provides insight into the expression pattern of B7-H3 in GC of Western origin. In GCs with higher level of B7-H3 expression, CD8+ T cells were spatially suppressed in the tumour centre suggesting that B7-H3 might be involved in tumour escape mechanisms from the immune response.publishersversionPeer reviewe

In memoriam Prof. Dr. med. Klaus-Peter Jünemann (1956–2023)

Nachruf auf den ehemaligen Professor für Urologie und Kinderurologie und Klinikdirektor am Universitätsklinikum Schleswig-Holstein (UKSH), Klaus-Peter Jünemann, der Ende August 2023 starb.Obituary for the former Professor of Urology and Pediatric Urology and Clinic Director at the University Hospital Schleswig-Holstein (UKSH), Klaus-Peter Jünemann, who died at the end of August 2023

Reassessment of sst3 Somatostatin Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-5

Background: Among the five somatostatin receptors (sst1-sst5), the sst3 receptor displays a distinct pharmacological profile. Like sst2, the sst3 receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike sst2, however, internalized sst3 receptors are rapidly transferred to lysosomes for degradation. Apart from this, very little is known about the clinical relevance of the sst3 receptor, which may in part be due to the lack of specific monoclonal sst3 antibodies. Methods: Here, we have extensively characterized the novel rabbit monoclonal anti-human sst3 antibody UMB-5 using transfected cells and receptor-expressing tissues. UMB-5 was then subjected to immunohistochemical staining of a series of 190 formalin-fixed, paraffin-embedded normal and neoplastic human tissues. Results: Specificity of UMB-5 was demonstrated by detection of a broad band migrating at a molecular weight of 70,000–85,000 in immunoblots from human pituitary. After enzymatic deglycosylation, the size of this band decreased to a molecular weight of 45,000. Tissue immunostaining was completely abolished by pre-adsorption of UMB-5 with its immunizing peptide. In addition, UMB-5 detected distinct cell populations in human tissues like pancreatic islands, anterior pituitary, adrenal cortex, adrenal medulla, and enteric ganglia, similar to that seen with a rabbit polyclonal antibody generated against a different carboxyl-terminal epitope of the sst3 receptor. In a comparative immunohistochemical study, UMB-5 yielded predominant plasma membrane staining in the majority of pituitary adenomas, pheochromocytomas, and a subset of neuroendocrine tumors. The sst3 receptor was also present in many glioblastomas, pancreatic, breast, cervix, and ovarian carcinomas. Conclusion: The rabbit monoclonal antibody UMB-5 may prove of great value in the identification of sst3-expressing tumors during routine histopathological examinations. Given its unique trafficking properties, these tumors may be potential candidates for sst3-directed receptor radiotherapy

Intratumoral heterogeneity affects tumor regression and Ki67 proliferation index in perioperatively treated gastric carcinoma

Background Intratumoral heterogeneity (ITH) is a major problem in gastric cancer (GC). We tested Ki67 and tumor regression for ITH after neoadjuvant/perioperative chemotherapy. Methods 429 paraffin blocks were obtained from 106 neoadjuvantly/perioperatively treated GCs (one to five blocks per case). Serial sections were stained with Masson's trichrome, antibodies directed against cytokeratin and Ki67, and finally digitalized. Tumor regression and three different Ki67 proliferation indices (PI), i.e., maximum PI (KiH), minimum PI (KiL), and the difference between KiH/KiL (KiD) were obtained per block. Statistics were performed in a block-wise (all blocks irrespective of their case-origin) and case-wise manner. Results Ki67 and tumor regression showed extensive ITH in our series (maximum ITH within a case: 31% to 85% for KiH; 4.5% to 95.6% for tumor regression). In addition, Ki67 was significantly associated with tumor regression (p < 0.001). Responders (<10% residual tumor, p = 0.016) exhibited prolonged survival. However, there was no significant survival benefit after cut-off values were increased ≥20% residual tumor mass. Ki67 remained without prognostic value. Conclusions Digital image analysis in tumor regression evaluation might help overcome inter- and intraobserver variability and validate classification systems. Ki67 may serve as a sensitivity predictor for chemotherapy and an indicator of ITH