RESUMEN
Background: Primary hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare tumour of vascular origin with an incidence of <0.1 cases per 100,000 people worldwide. Case description: A 29-year-old female with the history of epigastric pain and unintentional weight loss (3 kg over six months) was referred for upper endoscopy. The examination was without visual pathological findings, but a rapid urease test was positive. First-line treatment with clarithromycin-containing triple therapy for Helicobacter pylori infection was given. After completion of eradication therapy, diffuse abdominal pain developed. An abdominal computed tomography (CT) showed multiple liver nodules. Three consecutive core liver biopsies were performed and were inconclusive. A subsequent surgical liver nodule resection was performed. Histopathology of the specimen revealed grade 2 hepatocellular carcinoma; bone scintigraphy was negative for metastasis. A multidisciplinary team (MDT) recommended giving the patient sorafenib, which was poorly tolerated. The histology was reviewed using immunohistochemistry staining at the request of the oncologist, which showed expression of CD31 and CD34. Based on clinical, morphological and immunohistochemistry findings, a diagnosis of hepatic epithelioid hemangioendothelioma was made. Based on the multidisciplinary team's findings, liver transplantation was indicated as the only curative treatment. Conclusion: Because of the rarity of this disease, combining clinical, radiological and histopathological methods as well as an MDT approach can help to reach the correct final diagnosis. As demonstrated in this clinical case, it is crucial to perform immunohistochemistry of a liver biopsy to confirm a HEHE diagnosis. LEARNING POINTS: Hepatic epithelioid hemangioendothelioma is a rare vascular tumour that is often misdiagnosed and mismanaged.This case emphasises the critical importance of interdisciplinary teamwork and the use of non-invasive and invasive techniques to achieve a definitive diagnosis.
RESUMEN
Background: Non-islet cell tumor-induced hypoglycemia (NICTH) is a rare, life-threatening medical condition caused by excessive insulin-like growth factor II (IGF-II) secretion from tumors of most commonly mesenchymal origin. Using next-generation sequencing, we have characterized the genome and transcriptome of the resected IGF-II-secreting solitary fibrous tumor from a patient with severe hypoglycemia accompanied by hypoglycemia unawareness. Case presentation: A 69-year-old male patient presenting with abdominal discomfort was examined using computer tomography, revealing a large lesion at the lesser pelvis extending above the umbilicus. As no bone and lymph node metastases were detected, the patient was scheduled for laparotomy. Before surgery, the patient presented with symptoms of severe hypoglycemia. Suppressed C-peptide levels and subsequent hypokalemia indicated a possible case of NICTH. The patient was treated with methylprednisolone (8 mg) to assess hypoglycemia. After the surgery, mild hypoglycemia was present for the postoperative period, and no radiological recurrences were observed 3 and 12 months after discharge. Histopathological examination results were consistent with the diagnosis of malignant solitary fibrous tumor (SFT). Overexpression of IGF-II was confirmed by both immunohistochemistry and RNA sequencing. Further NGS analysis revealed an SFT characteristic alteration-NAB2-STAT6 fusion. Additionally, three deleterious missense variants were detected in oncogenes BIRC6, KIT, and POLQ, and one homozygous in-frame deletion in the RBM10 tumor suppressor gene. Conclusion: While the NAB2-STAT6 fusions are well characterized, the mutational landscape of SFTs remains understudied. This study reports the importance of NGS to characterize SFTs as we detected four coding variants in genes (BIRC6, KIT, POLQ, and RBM10) associated with tumorigenesis that could potentially contribute to the overall pathogenesis of SFT.
RESUMEN
INTRODUCTION: MPNST is a rare type of malignancy classified as malignant soft tissue sarcoma. One-fourth to one-half of MPNST arise in patients with neurofibromatosis type 1 (NF1) and generally involves major nerve trunks of proximal extremities and body, rarely head and neck region. Aggressive nature of the disease shows poor overall prognosis, where treatment modalities are also limited. PRESENTATION OF CASE: 62-year-old otherwise healthy female underwent radical surgical treatment due to the mass of the right side of the neck. Preoperative MRI studies showed well defined partly cystic and visually malignant neoplasm of the carotid sheath in upper third of the neck. Well-defined tumor of the right vagus nerve was detected during the surgery and was excised with safe and radical margins. Further histological study confirmed MPNST diagnosis. Defect of the vagus nerve was reconstructed with a nerve grafts to maintain and improve patients quality of the life. Adjuvant radiotherapy was appointed. At one year follow-up period no evidence of disease recurrence was found. Nevertheless, patient reported significant improvement of functionality and less vagus nerve impairment symptoms. DISCUSSION: In this article we discuss main epidemiological data of MPNST as well as distinction of our clinical case peculiarities from data mentioned in literature. CONCLUSION: MPNST are described as aggressive neoplasms with unfavorable short and long-term prognosis. Early diagnosis and radical surgical intervention not only improve patient prognosis but also allow to use additional treatment options to improve patients survival and quality of the life even in case of MPNST.
RESUMEN
Hotspot mutations of the BRAF and NRAS genes are the most common genetic alterations in invasive cutaneous melanoma; however, the prognostic significance of BRAF and NRAS co-mutations remains controversial. The present study aimed to determine the association between NRAS and BRAF mutation status and the clinicopathological characteristics of patients with stage IA-IIC melanoma. A total of 118 patients who underwent surgical treatment for stage IA-IIC melanoma at the Riga East University Hospital between 2012 and 2018 were retrospectively enrolled in the present study. BRAF and NRAS mutation status was assessed by digital droplet PCR using the BRAFV600, NRAS Q61 and NRAS G12/G13 Screening Assays. The association between mutation status and clinicopathological features and progression-free survival (PFS) was then analyzed. The BRAF V600 mutation was detected in 67 out of 118 patients (56.8%). The PFS did not differ between patients with BRAF wild-type and BRAF-mutant melanoma. NRAS mutations were detected in 35 out of 118 patients (29.6%). The NRAS mutational status was associated with Breslow thickness (P=0.035), tumor type (P=0.020; χ2=0.20), mitotic rate (P=0.025) and lymphovascular invasion (P=0.02; χ2=0.20). Patients with NRAS-mutant melanoma had significantly worse PFS compared with NRAS wild-type melanoma (HR=12.30; 95% CI=5.78-26.21, P<0.0001). Furthermore, BRAF and NRAS co-mutant melanoma was associated with a significantly worse PFS compared with BRAF-mutant melanoma (HR=6.30; 95% CI=3.10-12.70, P<0.0001). In conclusion, NRAS-mutant and NRAS/BRAF co-mutant stage IA-IIC melanoma was associated with worse PFS compared with NRAS wild-type and BRAF-mutant melanoma. The assessment of NRAS mutation status in melanoma in routine clinical practice may be beneficial for the risk stratification of disease progression for primary non-metastatic malignant melanoma.
RESUMEN
We aimed to determine the diagnostic value of anti-parietal cell antibodies (anti-PCA), anti-intrinsic factor antibodies (anti-IFA), pepsinogen ratio (PGI/II), and gastrin-17 (G-17) in corpus-restricted atrophic gastritis (CRAG) detected by ELISA (Inova, Biohit). Our study compared 29 CRAG cases against 58 age- and sex-matched controls with mild or no atrophy. Anti-PCA and anti-IFA positive cutoff values were ≥25 units for both. PGI/II value <3 was considered characteristic for atrophy; positive cutoff values for G-17 and anti-H. pylori IgG were >5 pg/L and >30 EIU. Anti-PCA was positive in 65.5% For CRAG cases and 13.8% of the controls (p < 0.0001), anti-IFA was positive in 13.8% and 0% (p = 0.01), respectively. Decreased pepsinogen levels were present in 79.3% of CRAG cases and 10.3% of the controls (p < 0.0001). PGI/II ratio was the best single biomarker, with sensitivity = 79%, specificity = 90%, and AUC 0.90. The combined use of PGI/II and anti-PCA resulted in AUC 0.93 for detecting CRAG. Our study suggests that the best combination of non-invasive biomarkers for detecting CRAG is PGI/II with anti-PCA. The addition of G-17 and anti-IFA is of little utility in clinical application.
RESUMEN
Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and medical communities; therefore, the authors believe it is relevant to share their observations.
Asunto(s)
Melanoma , Virus Oncolíticos , Neoplasias Cutáneas , Enterovirus Humano B , Humanos , Melanoma/terapia , Neoplasias Cutáneas/terapia , Melanoma Cutáneo MalignoRESUMEN
Introduction−−Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods−−Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results−−Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4−31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33−45% while specificity decreased (range: 61.1−62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions−−Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage.
RESUMEN
INTRODUCTION: Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. METHODS: The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. RESULTS: Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. CONCLUSIONS: CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.
RESUMEN
BACKGROUND: Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. AIMS: To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. METHODS: Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. RESULTS: In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serology-negative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. CONCLUSIONS: Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.
RESUMEN
Tumor-infiltrating lymphocytes (TILs) in primary cutaneous melanoma are considered to represent the host's antitumor immunological response; however, whether there are associations between TIL grade and histopathological characteristics and disease survival remains controversial. BRAF mutational status has been established as a routine screening method in advanced malignant melanoma, and worse prognosis rates have been demonstrated in patients harboring BRAF mutations. However, the general impact of BRAF mutational status on survival and histopathological characteristics is still debated. The aim of the present study was to compare the value of the assessment of TIL grade in stages I-II nodular and superficial spreading melanoma and BRAF mutational status, and its influence on clinicopathological characteristics. Altogether, 85 patients at stage IA-IIC who underwent melanoma surgical treatment at the Riga East University Hospital between 2012 and 2017 were retrospectively enrolled in the study. The histopathological characteristics were assessed according to the current World Health Organization and The American Joint Committee on Cancer 8th edition guidelines. The current study showed that patients with melanoma with high TIL grade had significantly better progression-free survival than patients with low TIL grade (hazard ratio, 4.9; 95% CI, 2.3-11.2; P<0.0001). BRAF mutations were observed in 52 patients (61.2%). BRAF mutational status in melanoma was associated with Clark invasion level (P=0.045), patient age (P=0.02) and TIL (P=0.04). The assessment of TIL grade in stage I-II melanoma demonstrated prognostic significance value and may help improve risk assessment in the future.
RESUMEN
The use of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Assessment based on Intestinal Metaplasia (OLGIM) staging system is recommended for identifying subjects at risk for developing gastric cancer; usually high-risk lesions are considered only as stages III and IV. Accumulating evidence suggests that incomplete intestinal metaplasia (IM) is important in the development of gastric cancer. Our aim has been to identify the prevalence of incomplete IM in patients with low-risk OLGA/OLGIM stages among a high-risk general population. Healthy adult volunteers aged 40-64 years were invited to undergo upper endoscopy within a regional GISTAR pilot study in Kazakhstan (n = 166). Gastric lesions were staged according to OLGA/OLGIM staging system. High iron diamine-alcian blue (HID-AB) was used for subtyping IM. IM prevalence overall was 45.8%. Incomplete IM was present in 52.6% (type II in 30.3% and type III in 22.3%), whereas complete IM was found in 47.4% individuals. The prevalence of OLGIM I and II stage were 39.8 and 4.8%, respectively, whereas OLGIM III was observed in 1.2%. The prevalence of incomplete IM in patients stratified to OLGIM I was 54.5% (type II in 31.8% and type III in 22.7%). High prevalence of incomplete IM was detected not only in subjects with extensive IM, but in those stratified as at the OLGIM I stage. Without IM subtyping, patients with high risk of gastric cancer development would be missed for surveillance.
Asunto(s)
Detección Precoz del Cáncer/métodos , Intestinos/patología , Neoplasias Gástricas/diagnóstico , Adulto , Biopsia , Femenino , Gastritis/patología , Voluntarios Sanos , Infecciones por Helicobacter/patología , Helicobacter pylori , Humanos , Masculino , Metaplasia/patología , Persona de Mediana Edad , Proyectos Piloto , Lesiones Precancerosas/patología , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/metabolismoRESUMEN
INTRODUCTION: Clostridium difficile is one of the most common healthcare-associated infections. Pseudomembranous colitis is a serious complication of Clostridium difficile infection (CDI) after septic surgery and antibacterial therapy. A sudden white blood cell (WBC) count increase and extremely high leucocytosis may be a predictor of a poor outcome. PRESENTATION OF CASE: A 77 years old male was hospitalised because of lower leg osteomyelitis and was operated. He received antibacterial treatment with Cefazolin for three days and then developed a high WBC count. The course of the disease was fulminant, with a rapid increase in the WBC count up to 132,000/mm3 and a septic shock, and required cardiovascular and ventilatory support. The patient was started on intravenous Metronidazole (500â¯mg every eight hours) and oral Vancomycin (500â¯mg every six hours). The patient's condition gradually improved over a period of six days. Then a hyperthermia above 39 degrees Celsius, hypotension and painful abdominal bloating developed, and the WBC count peaked to 186,000/mm3. The blood cultures were positive for Klebsiella pneumoniae. The patient died. DISCUSSION: In our case, we describe a community-onset, healthcare-facility-associated, severe CDI complicated by a blood stream infection. The administration of oral Vancomycin, which is highly active against the intestinal flora, could have been responsible for the persistence and overgrowth of Klebsiella pneumoniae. CONCLUSIONS: Severe CDIs after orthopaedic surgery and antibacterial treatment complicated by the development of nosocomial infection significantly worsen the prognosis of the disease. Careful consideration of antibacterial therapy and early symptom recognition may help prevent catastrophic events.
RESUMEN
Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression-free survival are good.
RESUMEN
Melanoma is an aggressive skin cancer form with a grave prognosis. Current results suggest that oncolytic virus treatment of melanoma has a high therapeutic potential. ECHO-7 (Rigvir) is the first oncolytic virus registered in Latvia. A female patient was diagnosed with stage IIIB melanoma in December 2012, over 9.4 years ago. After the first excision and re-excision, the patient had several recurrences and disease progressions. After the patient had received surgical treatment in 2014, ECHO-7 virus oncolytic virotherapy was started. Since then, the patient has experienced only one more disease progression episode in May 2015 and has been stable for over 60 months. The patient has not received any other treatment than surgery and oncolytic virotherapy. No severe adverse events have been reported during virotherapy. The present case suggests that ECHO-7 virotherapy is an effective treatment of skin melanoma.
RESUMEN
Adrenal gland melanoma is an extremely rare diagnosis with less than 20 cases reported. The criteria for diagnosing adrenal gland melanoma include involvement of only one adrenal gland, presence of melanin pigment in the histological examination of the tumor tissue, no primary melanoma tumor in any other organ, and no history of resection of pigmented lesions. However, it is complicated to rule out melanoma of unknown primary origin. Here we report a female patient who at the age of 75 years was admitted to hospital due to suspicion of adrenal and gastric tumor. The largest tumor was found in the adrenal gland, thus leading to the diagnosis of primary adrenal gland melanoma presenting metastases in the stomach. The melanoma was BRAF wild type. Due to the rarity of this disease, there is no standard treatment. After two subsequent surgeries, treatment with the ECHO-7 oncolytic virus Rigvir was started. The patient has received oncolytic virotherapy for 5 years and 1 month and has been stable since then with good tolerability. The therapy is still ongoing. Adrenal gland melanoma is an extremely rare diagnosis and therefore it is important to discuss the diagnostic criteria and possible treatments.
RESUMEN
BACKGROUND: The identification of novel biomarkers for the early detection and monitoring of gastric (GC) and colorectal cancer (CRC) is of paramount importance. TM9SF4 is a newly described V-ATPase interacting protein involved in the malignant progression of cancer cells. While TM9SF4 expression pattern and cellular localization have been described in in vitro in tumor cell lines of different histotypes, its expression in gastrointestinal tumor tissues has never been investigated. METHODS: In this study, we detected by immunohistochemistry (IHC) in tumor and surrounding healthy tissues TM9SF4, in comparison with clinically adopted biomarkers CEA and CA 19-9 to evaluate TM9SF4 potential as a novel tissue marker for early detection and monitoring of GC and CRC cancers. RESULTS: The expression of TM9SF4, CEA and CA 19-9 was evaluated in samples from 108 cancer patients (68 with GC and 40 CRC) and in healthy tissues from 20 non-cancer patients. Our results clearly suggest that TM9SF4 expression was significantly increased in GC and CRC samples and significantly correlated to disease stage in both cancer types. CONCLUSIONS: We propose TM9SF4 as highly specific cancer biomarker, exploitable for disease detection and staging of gastrointestinal cancers patients, with tumor tissue levels of expression outperforming those of clinically adopted markers such as CEA and CA 19-9.
RESUMEN
BACKGROUND: Atrophic gastritis is considered precursor condition for gastric cancer. There is so far limited evidence on the performance of pepsinogens for atrophy detection in Central Asia. The aim of our study was to detect the prevalence of atrophic gastritis in the asymptomatic adult population in Kazakhstan as well as address the accuracy of pepsinogen testing in atrophy detection. METHODS: Healthy individuals aged 40-64 were included. Upper endoscopy and pepsinogens (PG) evaluation were performed. PG were analysed in plasma by latex agglutination. Cut off values were used to define decreased PG values (PGR ≤ 3 and PG I ≤ 70 ng/mL); severely decreased PG values (PGR ≤ 2 and PG I ≤ 30 ng/mL). Biopsies were analyzed and obtained according to the updated Sydney System. PG test sensitivity, specificity and overall accuracy were assessed using the histological diagnosis as the "gold standard". RESULTS: Altogether 157 individuals - female 40,1% and male 59,9% were included. Histologically, moderate to severe corpus atrophy, was present only in 1,3% cases. From all study subjects, 26,8% had decreased plasma PG values with cut-off values PGR ≤ 3 and PG I ≤ 70 ng/mL. The sensitivity of the PG test with this cut-off values was 50,0%, specificity 73,5%, overall accuracy 73,2% for detection of moderate to severe atrophy in the corpus. The sensitivity of PG test with cut-off values PGR ≤ 2 and PG I ≤30 ng/mL was 50,0%, specificity 90,9% and overall accuracy 90,4%. CONCLUSIONS: The prevalence of gastric mucosal atrophy was low in the Kazakh population. Serological PG test screening nevertheless can play an important role in the diagnosis of gastric precancerous lesions. However, the diagnostic accuracy of the PG test is mainly dependent on the cut-off values for positive results.
Asunto(s)
Mucosa Gástrica/patología , Gastritis Atrófica/epidemiología , Pepsinógeno A/sangre , Adulto , Atrofia/sangre , Atrofia/diagnóstico , Atrofia/epidemiología , Endoscopía , Femenino , Estudios de Seguimiento , Mucosa Gástrica/metabolismo , Gastritis Atrófica/sangre , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/patología , Humanos , Kazajstán/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Curva ROCRESUMEN
RATIONALE: Of all the parts of the larynx, the glottis has the highest frequency of cancer. With disease progression, the vocal cord movement is affected and for advanced stages its anatomical and functional preservation is rarely achievable, if at all. PATIENT CONCERNS: Here we describe a 72-year-old patient who presented with hoarseness for a year and was only able to whisper. DIAGNOSIS: A computed tomography (CT) scan of the vocal cords (without contrast) showed higher density tissue. Histological examination disclosed a well-differentiated verrucous squamous cell carcinoma of the glottis. INTERVENTIONS: The patient was treated with the oncolytic ECHO-7 virus Rigvir without any of the standard treatments. OUTCOMES: As shown by CT scans, the patient has been stabilized, and the laryngeal functions are preserved with the virotherapy still ongoing. The patient was diagnosed over 4.2 years ago. LESSONS: Considering the present patient being treated with Rigvir without any standard treatment, the results suggest that Rigvir therapy could be a possible treatment for glottic cancer.
Asunto(s)
Neoplasias Laríngeas/terapia , Viroterapia Oncolítica/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Anciano , Glotis/diagnóstico por imagen , Glotis/patología , Humanos , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/patología , Masculino , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer has been proposed to be a distinct gastric cancer molecular subtype. The prognostic significance of EBV infection in gastric cancer remains unclear and needs further investigation. Our study aimed to analyze EBV-positive and EBV-negative gastric cancer patients regarding their personal and tumor-related characteristics, and compare their overall survival. METHODS: Gastric cancer patients consecutively treated at the Riga East University Hospital during 2009-2016 were identified retrospectively. Tumor EBV status was determined by in-situ hybridization for EBV-encoded RNA (EBER). Information about clinicopathological characteristics was obtained from patient questionnaires, hospital records. Overall survival was ascertained through 30 July 2017. Cox proportional hazard regression models adjusted for personal and tumor-related covariates compared survival between EBV-positive and EBV-negative patients. RESULTS: There were a total of 302 gastric cancer patients (61% males) with mean and SD age 63.6 ± 11.5 years. EBER positivity was present in 8.6% of tumors. EBV-positive gastric cancer patients had better survival at 80 months [adjusted hazard ratio = 0.37, 95% confidence interval (CI) = 0.19-0.72] compared to EBV-negative patients. Worse survival was observed for patients with stage III (hazard ratio = 2.76, 95% CI = 1.67-4.56) and stage IV (hazard ratio = 10.02, 95% CI = 5.72-17.57) compared to stage I gastric cancer, and overlapping and unspecified subsite (hazard ratio = 1.85; 95% CI = 1.14; 3.00) compared to distal tumors. CONCLUSION: Tumor EBV positivity is a favorable prognostic factor in gastric cancer.
Asunto(s)
Adenocarcinoma/patología , Infecciones por Virus de Epstein-Barr/patología , Neoplasias Gástricas/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/mortalidad , Adenocarcinoma/virología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Letonia/epidemiología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Sobrepeso/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Distribución por Sexo , Fumar/epidemiología , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/virología , Tasa de Supervivencia , Adulto JovenRESUMEN
Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR = 3.4; p-trend = 0.004), interleukin (IL)-10 (OR = 2.4; p-trend = 0.019), CCL19 (OR = 2.3; p-trend = 0.019), CCL11 (OR = 2.2; p-trend = 0.026), IL-17A (OR = 2.0; p-trend = 0.038) and CCL8 (OR = 1.9; p-trend = 0.049). Systemic responses to EBV-positive gastric cancer are characterized by alterations in chemokines and PD-L1. Profiling of these molecules may enable non-invasive diagnosis of EBV status when tumor tissue is unavailable. Our findings provide theoretical justification for clinical evaluations of immune checkpoint therapy for EBV-positive gastric cancer.