Schwannoma of the phrenic nerve. A case report.

BACKGROUND: Neurogenic tumors are the third most common tumors occurring within the mediastinum. Predominantly completely asymptomatic, they are most often found in the posterior mediastinum, although they may also be located, albeit rarely, in the middle mediastinum. Thus, in the cases of tumors localized in the middle mediastinum, schwannomas of the phrenic nerve must always be considered. CASE REPORT: In this case, a male patient presented with a tumor of the middle mediastinum. PET/CT scan determined that it was a circumscribed tumor without signs of dissemination. However, due to the tumor's location, a preoperative biopsy of the tumor was not possible. Therefore, the patient underwent videothoracoscopic extirpation of the tumor, including the necessary resection of the phrenic nerve that passed through the centre of the tumor. Subsequent histological analysis definitively confirmed a schwannoma with low proliferative activity. CONCLUSIONS: Differential diagnosis of mediastinal tumours is very difficult; however, in the case of circumscribed tumours not invading the surrounding tissues, proceeding to surgical revision, with the complete removal of the tumour, is possible, even without determining the histological nature. Minimally invasive surgical techniques dominate the treatment of neurogenic tumors of the mediastinum; they are associated with minimal complications and allow a rapid return of the patient to their normal activities.

Microbiota Diversity in Non-Small Cell Lung Cancer Gut and Mouth Cavity Microbiota Diversity in Non-Small Cell Lung Cancer Patients.

Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.

Exome sequencing reveals IFT172 variants in patients with non-syndromic cholestatic liver disease.

BACKGROUND AND AIM: Gene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis. PATIENTS AND METHODS: Both paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible. WES was used for reassessment of 34 patients (23 children) without diagnostic genotypes in ABCB11, ATP8B1, ABCB4 or JAG1 demonstrable by previous Sanger sequencing, and for primary assessment of additional 17 patients (10 children). Nasopharyngeal swab mRNA was analysed to address variant pathogenicity in two families. RESULTS: WES revealed biallelic variation in 3 ciliopathy genes (PKHD1, TMEM67 and IFT172) in 4 clinically unrelated index subjects (3 children and 1 adult), heterozygosity for a known variant in PPOX in one adult index subject, and homozygosity for an unreported splice-site variation in F11R in one child. Whereas phenotypes of the index patients with mutated PKHD1, TMEM67, and PPOX corresponded with those elsewhere reported, how F11R variation underlies liver disease remains unclear. Two unrelated patients harboured different novel biallelic variants in IFT172, a gene implicated in short-rib thoracic dysplasia 10 and Bardet-Biedl syndrome 20. One patient, a homozygote for IFT172 rs780205001 c.167A>C p.(Lys56Thr) born to first cousins, had liver disease, interpreted on biopsy aged 4y as glycogen storage disease, followed by adult-onset nephronophthisis at 25y. The other, a compound heterozygote for novel frameshift variant IFT172 NM_015662.3 c.2070del p.(Met690Ilefs*11) and 2 syntenic missense variants IFT172 rs776310391 c.157T>A p.(Phe53Ile) and rs746462745 c.164C>G p.(Thr55Ser), had a severe 8mo cholestatic episode in early infancy, with persisting hyperbilirubinemia and fibrosis on imaging studies at 17y. No patient had skeletal malformations. CONCLUSION: Our findings suggest association of IFT172 variants with non-syndromic cholestatic liver disease.

Fluorescence In Situ Hybridization in Primary Diagnosis of Biliary Strictures: A Single-Center Prospective Interventional Study.

Background and aims: Diagnosis of the biliary stricture remains a challenge. In view of the low sensitivity of brush cytology (BC), fluorescence in situ hybridization (FISH) has been reported as a useful adjunctive test in patients with biliary strictures. We aimed to determine performance characteristics of BC and FISH individually and in combination (BC + FISH) in the primary diagnosis of biliary strictures. Methods: This single-center prospective study was conducted between April 2019 and January 2021. Consecutive patients with unsampled biliary strictures undergoing first endoscopic retrograde cholangiopancreatography in our institution were included. Tissue specimens from two standardized transpapillary brushings from the strictures were examined by routine cytology and FISH. Histopathological confirmation after surgery or 12-month follow-up was regarded as the reference standard for final diagnosis. Results: Of 109 enrolled patients, six were excluded and one lost from the final analysis. In the remaining 102 patients (60.8% males, mean age 67.4, range 25-92 years), the proportions of benign and malignant strictures were 28 (27.5%) and 74 (72.5%), respectively. The proportions of proximal and distal strictures were 26 (25.5%) and 76 (74.5%), respectively. In comparison to BC alone, FISH increased the sensitivity from 36.1% to 50.7% (p = 0.076) while maintaining similar specificity (p = 0.311). Conclusions: Dual-modality tissue evaluation using BC + FISH showed an improving trend in sensitivity for the primary diagnosis of biliary strictures when compared with BC alone.

Clear cell mesotheliomas with inactivating VHL mutations and near-haploid genomic features.

Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of clear cell mesothelioma remained limited. In this study, we identified an index patient with clear cell mesothelioma, confirmed by immunohistochemical and ultrastructural studies. Targeted next-generation sequencing revealed the presence of an inactivating VHL mutation. We then systematically searched for VHL-mutant mesotheliomas in a comprehensive genomic profiling database of 1532 mesotheliomas. Collectively, we identified a cohort of four VHL-mutant clear cell mesotheliomas, including three peritoneal and one pleural tumors from three females and one male, with age range of 47-68 (median 63) years. Histologically, each tumor showed a microcystic to tubulopapillary architecture with prominent clear cells. By next-generation DNA sequencing, each of the four clear cell mesotheliomas harbored inactivating VHL mutations, while lacking other alterations typical of mesotheliomas such as BAP1, NF2, SETD2, CDKN2A, CDKN2B, TP53, and PTEN. By using low-pass whole genome sequencing on the index case and targeted next-generation sequencing on the remaining three cases, we identified extensive loss of heterozygosity throughout the genome but consistently sparing chromosomes 5, 7, and 20, characteristic of genomic near-haploidization. In summary, clear cell mesotheliomas were characterized by inactivating VHL mutations and genomic near-haploidization and appeared to represent a distinct clinicopathologic and molecular category of mesotheliomas. Our findings implicate VHL in the pathogenesis of a subset of mesotheliomas, particularly those with clear cell morphology.

The Role of Cytoreductive Nephrectomy in Renal Cell Carcinoma with Sarcomatoid Histology: A Case Series and Review of the Literature.

BACKGROUND: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. PATIENT AND METHODS: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. RESULTS: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. CONCLUSION: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters.

Spontaneous liver rupture following SARS-CoV-2 infection in late pregnancy: A case report.

BACKGROUND: Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by systemic inflammatory response syndrome and vasculopathy. SARS-CoV-2 associated mortality ranges from 2% to 6%. Liver dysfunction was observed in 14%-53% of COVID-19 cases, especially in moderate severe cases. However, no cases of spontaneous hepatic rupture in pregnant women with SARS-CoV-2 have been reported. CASE SUMMARY: A 32-year-old pregnant patient (gestational age: 32 wk + 4 d) without any remarkable medical history or long-term medication presented with epigastralgia. Infectious, non-infectious, and pregnancy-related hepatopathies were excluded. Sudden onset of right subcostal pain with D-dimer and liver enzyme elevation was followed by shock with thrombocytopenia. While performing an emergency cesarean section, hemoperitoneum was observed, and the patient delivered a stillbirth. A 6-cm liver rupture at the edges of segments V and VI had occurred, which was sutured and drained. SARS-CoV-2 positivity on reverse transcription-polymerase chain reaction was confirmed. Further revisions for intrahepatic hematoma with hemorrhagic shock and abdominal compartment syndrome were performed. Subsequently, the patient developed hemoptysis, which was treated using bronchoscopic therapy and non-invasive ventilation. Liver tissue biopsy revealed hemorrhagic foci and necrosis with an irregular centrilobular distribution. Antiphospholipid syndrome and autoimmune hepatitis were also ruled out. Fetal death was caused by acute intrauterine asphyxia. CONCLUSION: This case reveals that pregnant women with SARS-CoV-2 infection may be predisposed to liver parenchyma disease with liver rupture.

A Pathological Complete Response to the Combination of Ipilimumab and Nivolumab in a Patient with Metastatic Renal Cell Carcinoma.

Background and Objectives: Complete pathological response after ipilimumab and nivolumab combination therapy in a patient with intermediate prognosis renal cell carcinoma is an uncommon finding. Case presentation: A 60-year-old man presented with synchronous solitary metastatic bone lesion and renal cell carcinoma and achieved a complete pathological response after surgical resection of the bone lesion, followed by ipilimumab and nivolumab combination therapy and nephrectomy. The treatment was complicated by hypophysitis and oligoarthritis more than a year after the initiation of the therapy. Conclusions: Currently, the combination therapy based on immune checkpoint inhibitors represents the treatment of choice in patients with intermediate- and poor-risk prognosis metastatic renal cell carcinoma. In the present case, preoperative therapy with ipilimumab and nivolumab resulted in a complete pathological response in the renal tumor. Vigilance concerning potential immune-related side effects is warranted throughout the course of therapy and the subsequent follow-up.

HELLP syndrome and HELLP-like syndrome in pregnancies with covid-19 - case reports.

OBJECTIVE: We present two case reports of severe course of covid-19 in pregnancy demonstrating similarity between covid-19 and HELLP syndrome. CASE REPORT: The first case report describes an asymptomatic course of covid-19 accompanied by elevation of liver enzymes and lactate dehydrogenase but low ratio of angiogenic bio-markers. No severe pregnancy complication occurred. All laboratory results had normalized after recovering from covid-19. The second case report describes a patient with elevated liver enzymes and lactate dehydrogenase which preceded a respiratory failure. Furthermore, one of the most feared complication of pregnancy occurred, namely hepatic rupture. After a delivery, the condition of the patient had been improving only slowly. It is not clear whether this condition represented a severe course of covid-19 or a concurrence of covid-19 and HELLP syndrome. CONCLUSION: A severe course of covid-19 in pregnancy may cause a dia-gnostic dilemma for its similarity between covid-19 and a specific complication of pregnancy - HELLP syndrome. This might lead to an unnecessary intervention and iatrogenic prematurity or underestimation of symptoms and delayed dia-gnosis of HELLP syndrome.

Coexistent neck enteric cyst and intraspinal neurenteric cyst: Embryopathogenetic implications.

INTRODUCTION: Enteric cysts are very rare conditions, occurring mainly in the posterior mediastinum and posterior neck. Their pathomorphology corresponds with that of intraspinal neurenteric cysts. Both formations are derivatives of the posterior foregut. However, their embryopathogenesis has not been elucidated satisfactorily as yet. For those associated with vertebral anomalies, the split notochord theory has been widely accepted. However, this is be hardly conceivable for cases free of these anomalies. CASE REPORT: Here, a patient with concurrent separated enteric and neurenteric cysts and cervical spine dysmorphism is presented. DISCUSSION: The review of the relevant literature revealed sporadic analogical cases in which a transvertebral communication between the two cysts was present or absent. The latter was associated with a minimal abnormality of the vertebral body. CONCLUSION: The authors suggest that normal vertebrae may be formed in patients with enteric cysts, which would make the notochord-split theory plausible also for those free of spinal malformations.

Prognostic value of tumor-infiltrating lymphocytes (TILs) and their association with PD-L1 expression and DNA repair protein RAD51 in patients with resected non-small cell lung carcinoma.

OBJECTIVES: DNA repair proteins have emerged as potential predictors for immunotherapy response alongside PD-L1 expression, tumor-infiltrating lymphocytes (TILs) and tumor mutational burden. We analyzed expression of PD-L1, TILs count and expression of the homologous recombination (HR) protein RAD51, as potential prognostic factors in patients with resected non-small-cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Discovery set included 96 NSCLC patients from the University Hospital Olomouc (Czech Republic) and a replication set included 1109 NSCLC patients from University Hospital Zurich (Switzerland). Tissue microarrays (TMAs) were stained using the automated staining platform Ventana Benchmark Ultra with antibodies against RAD51,CD3, CD8, CD68 and PD-L1. RESULTS: Loss of nuclear RAD51 protein was associated with high TILs (r=-0.25, p = 0.01) and PD-L1 status (10.6 vs. 2.4 %, p = 0.012) in patients receiving neoadjuvant chemo-/radiotherapy (CT/RT). In silico analysis from the TCGA data set showed a negative relationship between RAD51 mRNA expression and CD45 (r = ‒0.422, p < 0.0001), CD68 (r = ‒0.326, p < 0.001), CD3 (r = ‒0.266, p < 0.001) and CD8 (r = ‒0.102, p < 0.001). RAD51 low/PD-L1 high patients were clustered as separate entity in the replication set and in TCGA dataset. High TILs status was significantly associated with improved OS in the replication set (unadjusted HR = 0.57, 95 % CI 0.42-0.76, p < 0.001). Similar results have been seen for CD3, CD8 and CD68. CONCLUSIONS: In conclusion, RAD51 nuclear loss is weakly associated with increased TILs and high PD-L1 at the time of surgery in curatively resected NSCLC and after prior exposure to neoadjuvant chemo- or radiotherapy. Both high TILs and RAD51 nuclear loss were confirmed as independent prognostic factors in curatively resected NSCLC.