Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms.

BACKGROUND: Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs. METHODS: The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored. RESULTS: Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively). CONCLUSIONS: LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.

Pulmonary fat embolism after cardiopulmonary resuscitation.

Pulmonary fat embolism (PFE) is usually observed in patients with long bone fractures, patients with extensive subcutaneous fat contusions or skin burns. Chest compressions during cardiopulmonary resuscitation (CPR) present powerful repetitive violence against victim's chest. Skeletal chest fractures are the most frequent complication of CPR, and probably the most important cause of PFE autopsy finding in persons, which have been resuscitated before death. The aim of the present paper was to investigate the prevalence and seriousness of PFE in non-survivors after out-of-hospital cardiac arrest. During autopsy, PFE can be diagnosed in 30 - 42 % of persons after unsuccessful CPR; skeletal chest fractures are associated with significantly higher prevalence of PFE. After successful CPR, fat embolism may contribute significantly to acute respiratory distress syndrome, or multiorgan failure. The issue of CPR associated injuries has two medical aspects - clinical and forensic. From clinical point of view, the presence of CPR associated injuries must be acknowledged when offering healthcare to patients after successful CPR. During autopsy, CPR associated injuries should be diagnosed and evaluated as these injuries may contribute to death or may be potentially lethal.

Case report: Gaucher disease in trepanobiopsy of 16yo woman examined for suspected myelodysplastic syndrome.

Gaucher disease is an autosomal recessive disease belonging to the so-called storage diseases. More than 300 mutations of the GBA1 gene encoding the β-glucocerebrosidase enzyme are known. It is a very rare disease in the Czech Republic. Currently 35 patients are treated. In our case report, we present the case of a 16 year old female patient attending the Clinic of Pediatric Medicine at the University Hospital in Ostrava. Since 2007, the patient has suffered prolonged thrombocytopenia, at the time with progression, and splenomegaly, which has not been further investigated. Trepanobiopsy was sent to the Department of Pathology with suspicion of myelodysplastic syndrome in May of 2018. In the biopsy examination, the individual bloodline did not show dysplastic features and the number of blasts was not increased. The marrow interstitium was 70% permeated with gaucher cells with intraplasmatic fibrous material. Cells were in the appearance of „crumpled paper“ and expressed CD68 in immunohistochemical stain and in histochemical examination of PAS and iron (Fe) staining. Based on a morphological finding, Gauchers disease was suspected. Repeated bone marrow aspirates were subsequently captured by gaucher cells, and a next biochemical examination showed a β-glucocerebrosidase enzyme decrease of activity. Gaucher disease is a progressive disease that requires early diagnosis with the onset of therapy.

The impact of standard protocol implementation on the quality of colorectal cancer pathology reporting.

BACKGROUND: The aim of the study is to assess the influence of standardized protocol implementation on the quality of colorectal cancer histopathology reporting. METHODS: A standardized protocol was created based on the recommendations of The College of American Pathologists. The impact of this protocol was measured by comparing frequencies of assessed parameters in histopathology reports before and after implementation. RESULTS: In total, 177 histopathology reports were included in this study. The numbers of harvested lymph nodes were 12.4 ± 5.2 (colon) and 12.6 ± 5.4 (rectum) before protocol; and 17.1 ± 6.5 (colon), and 16.6 ± 7.0 after protocol implementation; differences were statistically significant. The recommended minimum of 12 lymph nodes was not achieved in 42.8 % (colon) and 45.7 % (rectum) of specimens before, and in 10.4 % (colon) and 17.7 % (rectum) of specimens after protocol implementation; differences were statistically significant. There were no differences in histopathology assessment of proximal and distal resection margins, grading assessment, TNM staging recording, and number of positive findings of microscopic tumor aggressiveness. The findings of tumor budding, tumor satellites, and assessment of microscopic tumor aggressiveness were more frequent after protocol implementation. Histopathology reports of rectal specimens contained assessments of the macroscopic quality of mesorectum, circumferential resection margin, and neoadjuvant therapy effect (if administered) only after protocol introduction. CONCLUSIONS: A standardized protocol is a valuable and effective tool for improving the quality of histopathology reporting. Its implementation is associated with more precise specimen evaluation, higher numbers of harvested lymph nodes, and improved completeness of histopathology reports.

Pulmonary fat embolism in non-survivors after cardiopulmonary resuscitation.

BACKGROUND: Blunt trauma acting against the human body presents the fundamental cause of pulmonary fat embolism (PFE) and fat embolism syndrome. The aim of the present study was to investigate PFE in non-survivors after cardiopulmonary resuscitation (CPR). METHODS: This was a prospective cohort study conducted in University Hospital Ostrava, Czech Republic. Within a 4-year study period, all non-survivors after CPR because of out-of-hospital cardiac arrest were assessed for the study eligibility. The presence/seriousness of PFE was determined by microscopic examination of cryo-sections of lung tissue (staining with Oil Red O). RESULTS: In total, 106 persons after unsuccessful CPR were enrolled in the study. The most frequent cause of death in the study population (63.2% of cases) was cardiac disease (ischemic heart disease); PFE was not determined as the cause of death in any of our study cases. Sternal fractures were identified 66.9%, rib fractures (usually multiple) in 80.2% of study cases; the median number of rib fractures was 10.2 fractures per person. Serious intra-thoracic injuries were found in 34.9% of cases. Microscopic examination of lung cryo-sections revealed PFE in 40 (37.7%) study cases; PFE was most frequently evaluated as grade I or II. Occurrence of sternal and rib fractures was significantly higher in persons with PFE than between persons without PFE (p = 0.033 and p = <0.001). Number of rib fractures was also significantly higher in persons with PFE. The occurrence of serious intra-thoracic injuries was comparable in both our study groups (p = 0.089). CONCLUSIONS: PFE presents a common resuscitation injury which can be found in more than 30% of persons after CPR. Persons with resuscitation skeletal chest fractures have significantly higher risk of PFE development. During autopsy of persons after unsuccessful CPR, it is necessary to distinguish CPR-associated injuries including PFE from injuries that arise from other mechanisms.

Microplastics and additives in patients with preterm birth: The first evidence of their presence in both human amniotic fluid and placenta.

Considering the well documented, almost ubiquitous nature of microplastics in different environments, the exposure of pregnant women to microplastics may pose risks to the unborn children. The study focused on investigating the presence of microplastics in amniotic fluid and placenta, and brings the first evidence of the simultaneous presence of microplastics and additives in both human amniotic fluid and placentas. In total, 20 samples of amniotic fluid and placenta from 10 patients were analyzed for the presence of microplastics and plastic additives by Fourier transform infrared spectroscopy - attenuated total reflectance (FTIR-ATR) after alkaline digestion with KOH. In 9 out of 10 patients, microplastics or additives were found in amniotic fluid, placenta, or both. Specifically, 44 particles of microplastics and polymer additives were identified in all samples. Chlorinated Polyethylene (CPE) and Calcium zinc PVC Stabilizer with particle sizes between 10 and 50 µm prevailed. Although all women involved in this study, who provided placenta and amniotic fluid samples, experienced physiological, singleton pregnancies complicated with preterm prelabour rupture of membranes (PPROM), it is too early to draw any conclusions and more research is needed.

Unnecessary orchiectomy due to atypical sarcoidosis manifesting as a unilateral scrotal mass: a case report and literature review.

Sarcoidosis is a disease characterised primarily by lung tissue involvement. Extrapulmonary involvement, particularly in the genitourinary tract, is extremely rare, particularly when it comes to primary disease detection in this location. The gold standard in establishing a definitive diagnosis of sarcoidosis is a combination of the clinical picture, the results of imaging methods, and histopathological examination from the biopsy taken (thus ruling out other causes of granulomatous inflammation). However, it is common for the biopsy to be infeasible or for the patient to refuse such an examination, resulting in the neglect of this critical verification. We introduce the case of a young 29-year-old man of Czech nationality who had been complaining for some time about non-specific pain above the pubic bone and in the lower abdomen, which was combined with a painless enlargement of the right half of the scrotum. Due to suspected malignancy, it was, after considering clinical, imaging, and laboratory findings, decided to perform a radical orchiectomy as a treatment option. The histological examination revealed that it was not cancer, but rather a rare genitourinary form of extrapulmonary sarcoidosis. In this case, radical resection had been, therefore, unnecessary. We also present a review of the literature on published extrapulmonary, genitourinary, and testicular sarcoidosis cases. All the above demonstrates the importance of considering a possible atypical sarcoidosis manifestation and histological confirmation before pursuing radical solutions.

A unique case of AH-dominant type nodular pulmonary amyloidosis presenting as a spontaneous pneumothorax: a case report and review of the literature.

Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.

Atypical carcinoma detected after regression of a "benign" oral white lesion. A case report.

BACKGROUND: Unlike leukoplakia, the smokers' lesion - a type of oral white lesion spontaneously regressing following cessation of smoking - is generally considered a non-serious condition and there is no recommendation for subsequent follow-up of such patients. CASE REPORT: Here, however, we present the case of a patient (female, 56, smoker) in whom we detected a smoker's lesion which regressed completely, without any signs of abnormality or malignity. The only shadow of a doubt that led us to inviting her for another examination was an additional examination using a VELscope® autofluorescence device that revealed autofluorescence suppression on the site of the former lesion. Another examination one month later revealed a patch of epithelium with a normal color but a negligibly different light reflection in the center of the former lesion; VELscope® indicated the questionable area to still be suspect. Following excision using margins indicated by VELscope® (+2-3 mm), histopathology revealed a squamous cell carcinoma. The secondary excision was carcinoma free and even after 5 years, the carcinoma has not recurred. CONCLUSION: We would like to point out that apparent spontaneous regressions of oral white lesions following smoking cessation still need attention and close follow-up to make sure that a developing squamous cell carcinoma cannot pass undetected.

Congenital fetal heart defect - an agreement between fetal echocardiography and autopsy findings.

AIMS: To determine the frequency of pregnancy terminations due to prenatal congenital heart defect (CHD) and assess the agreement fetal echocardiography (FECHO) and autopsy findings. METHODS: The data were retrospectively assessed between 2008 and 2017 in a population of 116 698 live births. The correlations between the FECHO and autopsy findings were classified into five levels of agreement: complete, partial, altered diagnosis, disagreement, and unfeasible autopsy. RESULTS: Totally, 293 CHDs were identified and 49% of families (143/293) decided to terminate the pregnancy. In 1% (2/143) of cases, the autopsy could not be performed, for the other 99% (141/143), the pathologist confirmed the presence of CHDs. Complete agreement between FECHO and autopsy was achieved in 85% (122/143). In 10% (14/143) of cases, the pathologist found minor findings, which were not described in the FECHO. In 4% (5/143) of cases, the pathologist changed the main diagnosis. CONCLUSION: Altogether, the results indicated that FECHO is a highly sensitive method for the prenatal detection of CHD but is incapable of detecting the complete spectrum of cardiac defects. Autopsies verified the diagnosis, confirmed the overall impairment in the fetus, and provided data for further counselling of the affected family.

Technical development of a new semispherical radiofrequency bipolar device (RONJA): ex vivo and in vivo studies.

The aim of this study is to inform about the development of a new semispherical surgical instrument for the bipolar multielectrode radiofrequency liver ablation. Present tools are universal; however they have several disadvantages such as ablation of healthy tissue, numerous needle punctures, and, therefore, longer operating procedure. Our newly designed and tested semispherical surgical tool can solve some of these disadvantages. By conducting an in vivo study on a set of 12 pigs, randomly divided into two groups, we have compared efficiency of the newly developed instrument with the commonly used device. Statistical analysis showed that there were no significant differences between the groups. On average, the tested instrument RONJA had shorter ablation time in both liver lobes and reduced the total operating time. The depth of the thermal alteration was on average 4 mm larger using the newly tested instrument. The new radiofrequency method described in this study could be used in open liver surgery for the treatment of small liver malignancies (up to 2 cm) in a single application with the aim of saving healthy liver parenchyma. Further experimental studies are needed to confirm these results before clinical application of the method in the treatment of human liver malignancies.