Higher mortality risk from gynaecological neoplasms and non-Hodgkin's lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry.

OBJECTIVE: To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE. METHODS: Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. RESULTS: During 2016-2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin's lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133). CONCLUSIONS: Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin's lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully.

Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: a real-world analysis of clinical and pathologic characteristics and outcomes.

BACKGROUND: Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor prognosis and are challenging to treat. We described the clinicopathologic features and outcomes in the largest cohort of Central Nervous System (CNS) metastasis in GEC patients. METHODS: single-center retrospective study of GEC treated from 2007 to 2021. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of CNS diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used. RESULTS: Of 3283 GEC patients, 100 (3.04%) were diagnosed with BrM and 20 with LMC (0.61%). Patients with known human epidermal growth factor receptor 2 (HER2) status (N = 48), 60% were HER2 positive (defined as IHC 3 + or IHC 2+/FISH+). Among LMC patients most were signet-ring subtype (85%), and only 15% (2/13) were HER2 positive. Median survival was 0.7; 3.8; and 7.7 months in BrM patients treated with best supportive care, radiation, and surgery, respectively (p < 0.001). In LMC, median survival was 0.7 month in patients who had best supportive care (7/19) and 2.8 months for those who had whole brain radiation therapy (p = 0.015). Multivariate analysis showed worse outcomes in ECOG ≥ 2 (p = 0.002), number of BrM ≥ 4 (p < 0.001) and number of metastatic sites (p = 0.009). CONCLUSION: HER2 expression were enriched in patients with BrM, while it is uncommon in LMC. Patients treated with surgery followed by radiation had an improved OS in BrM and WBRT benefited patients with LMC.

Clinical retrospective analysis of peri-implant oral malignancies.

PURPOSE: Complications of implant prostheses have direct correlation with the increased use of implants for dental rehabilitation. In this study, we present cases of peri-implant oral malignancies (PIOM) around dental implants and a retrospective analysis of patients treated for PIOM. METHODS: The retrospective analysis was performed with patients treated for PIOM at the Department of Oral and Maxillofacial Surgery of the Seoul National University Dental Hospital between 2006 and 2014. The patient records were thoroughly screened for previous medical issues, human papilloma virus infections, and other clinical data with a focus on relevant information such as localization, time from implant insertion to the development of the carcinoma, implant type and prosthetic rehabilitation. RESULTS: Twenty-one patients were diagnosed with PIOM. The male-to-female ratio was 1.625. The mean age of the patients was 60.42 ± 9.35 years old. Three patients reported ongoing alcohol/tobacco consumption. Five patients had a history of previous oral cancer surgery or exhibited mucosal lesions. The time from implant placement until carcinoma diagnosis was 49.13 ± 33.63 months on average. Most PIOM patients (95.2%) were diagnosed with SCC. All patients had previously been treated for peri-implantitis. In 85.7% of the patients, prostheses were observed on the opposing teeth where PIOM occurred. CONCLUSION: Based on the review of these cases, it can be deduced that there is a possibility that implant treatment and galvanic currents between prosthesis may constitute an irritant and/or inflammatory cofactor which contributes to the formation and/or development of malignant tumors. Patients at potential risk may benefit from individualized recall intervals and careful evaluations.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review.

BACKGROUND: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. METHOD: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. RESULTS: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. CONCLUSION: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Clinical impact of coexistent chronic lymphocytic thyroiditis on central lymph node metastasis in low- to intermediate-risk papillary thyroid carcinoma: The MASTER study.

BACKGROUND: The clinicopathological impact of chronic lymphocytic thyroiditis on patients with papillary thyroid carcinoma patients is still controversial. This study aimed to evaluate the clinicopathologic differences and risk factors for central lymph node metastasis based on the presence of coexistent chronic lymphocytic thyroiditis in patients with low- to intermediate-risk papillary thyroid carcinoma. METHODS: The medical records of 1,022 patients with low- to intermediate-risk papillary thyroid carcinoma who underwent lobectomy and central neck dissection between June 2020 and March 2022 were reviewed. Differences in clinicopathological factors were analyzed in patients with papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis. Furthermore, risk factors for central lymph node metastasis in patients with low- to intermediate-risk papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis were evaluated. RESULTS: Among the 1,022 patients with low to intermediate-risk papillary thyroid carcinoma, 102 (10.0%) had coexisting chronic lymphocytic thyroiditis. Female sex (odds ratio = 3.536, P = .001, 95% confidence interval 1.781-8.069), a multifocal tumor (odds ratio = 2.162, P = .001, 95% confidence interval 1.358-3.395), and angiolymphatic invasion (odds ratio = 0.365, P < .001, 95% confidence interval 0.203-0.625) were independent factors associated with patients who had coexisting chronic lymphocytic thyroiditis compared to those without chronic lymphocytic thyroiditis. There were 358 (35%) patients who had central lymph node metastasis. Multivariate analysis showed that younger age (odds ratio = 0.667, P = .013, 95% confidence interval 0.482-0.555), male sex (odds ratio = 0.549, P < .001, 95% confidence interval 0.402-0.751), tumor size >1 cm (odds ratio = 1.454, P = .022, 95% confidence interval 1.053-2.003), extrathyroidal extension (odds ratio = 1.874, P < .001, 95% confidence interval 1.414-2.486), and angiolymphatic invasion (odds ratio = 3.094, P < .001, 95% confidence interval 2.339-4.101) were risk factors for central lymph node metastasis. Angiolymphatic invasion (odds ratio = 11.184, P < .001, 95% confidence interval 3.277-46.199) was identified as the sole independent risk factor for central lymph node metastasis in patients with papillary thyroid carcinoma with coexisting chronic lymphocytic thyroiditis. CONCLUSION: Our data suggest that patients with low to intermediate-risk papillary thyroid carcinoma with coexistent chronic lymphocytic thyroiditis exhibit different clinical features than patients with papillary thyroid carcinoma without chronic lymphocytic thyroiditis. Additionally, the presence of chronic lymphocytic thyroiditis may be considered a potential factor against central lymph node metastasis.

Thyroid hormone resistance and large goiter mimicking infiltrative carcinoma in a pediatric patient.

OBJECTIVES: Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c. CASE PRESENTATION: A 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms. CONCLUSIONS: This is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab.

OBJECTIVES: To determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas. METHODS: A retrospective, single institution study was conducted among women with recurrent or advanced MMRd or MSI-H endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Logistic regression was used for univariable and multivariable analyses. PFS and OS were estimated using the methods of Kaplan and Meier and modeled via Cox proportional hazards regression. Log-rank test was used for intergroup comparisons based on body mass index (BMI). RESULTS: Among the 44 patients included in the analysis, the median BMI was 32.9 (range 18.5-51.8). Median cycles of pembrolizumab given was 11.5 (range 2-37). Median follow-up was 33 months (range 5-61) with a response rate of 63.6% and stable disease rate of 75%. When stratified by obesity status (BMI≥30), disease control rate was 59.8% in patients with a BMI < 30 and 85.2% in patients with a BMI≥30 patients (p = 0.05). On multivariable analysis, obesity was associated with increased rate of disease control (OR 4.03, 95%CI 1.09, 28) while prior smoking was associated with decreased rate of disease control (OR 0.18, 95%CI 0.03, 0.85). PFS was significantly increased among patients with a BMI≥30 (p = 0.03) but OS was similar (p = 0.5). CONCLUSION: In this retrospective study, obesity is associated with increased rates of disease control and improved PFS in patients treated with pembrolizumab for recurrent or advanced MMRd/MSI-H endometrial adenocarcinomas.

Natural products for gastric carcinoma prevention and treatment: Focus on their antioxidant stress actions in the Correa's cascade.

BACKGROUND: Correa's cascade is a pathological process beginning from gastritis to gastric precancerous lesions, and finally to gastric carcinoma (GC). While the pathogenesis of GC remains unclear, oxidative stress plays a prominent role throughout the entire Correa's cascade process. Studies have shown that some natural products (NPs) could halt and even reverse the development of the Correa's cascade by targeting oxidative stress. METHODS: To review the effects and mechanism by which NPs inhibit the Correa's cascade through targeting oxidative stress, data were collected from PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases from initial establishment to April 2023. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as terpenoid, polyphenols and alkaloids, exert multistep antioxidant stress effects on the Correa's cascade. These effects include preventing gastric mucosal inflammation (stage 1), reversing gastric precancerous lesions (stage 2), and inhibiting gastric carcinoma (stage 3). NPs can directly impact the conversion of gastritis to GC by targeting oxidative stress and modulating signaling pathways involving IL-8, Nrf2, TNF-α, NF-κB, and ROS/MAPK. Among which polyphenols have been studied more and are of high research value. CONCLUSIONS: NPs display a beneficial multi-step action on the Correa's cascade, and have potential value for clinical application in the prevention and treatment of gastric cancer by regulating the level of oxidative stress.

Protocolización de estudios clínicos multicéntricos en la era digital. ¿Tiene utilidad la centralización de datos por un data-manager? / Protocolization of multicenter clinical studies in the digital era. Is useful data centralization by a data-manager?

Introducción En los estudios multicéntricos la protocolización de los datos es una fase crítica que puede generar sesgos, sobre todo en estudios clínicos con presupuesto limitado. El objetivo es analizar la concordancia y la confiabilidad de los datos obtenidos en un estudio multicéntrico clínico entre la protocolización del centro de origen y la protocolización centralizada mediante un data-manager. Método Estudio clínico multicéntrico de prevalencia nacional sobre un carcinoma familiar infrecuente, realizándose una doble protocolización de los datos: a)en el centro de origen, y b)centralizada con un data-manager. La concordancia se analiza para el global de los datos y para los dos subgrupos del proyecto: a)grupo a estudio (carcinoma familiar; protocolizan 30 investigadores) y b)grupo control (carcinoma esporádico; protocolizan 4). Las diferencias interobservador se evalúan mediante el índice de Kappa de Cohen. Resultados Se incluyen 689 pacientes: 252 del grupo a estudio y 437 del grupo control. Respecto al análisis de concordancia del estadio tumoral, se han objetivado un 2,5% de discordancias, siendo alta la concordancia entre protocolizadores (Kappa=0,931). Respecto a la valoración del riesgo de recidiva, las discordancias fueron del 7% de los casos, siendo alta la concordancia (Kappa=0,819). Respecto a la clasificación ecográfica TIRADS, las discordancias son del 6,9% y la concordancia es alta (Kappa=0,922). Se han detectado un 4,6% de errores de transcripción. Conclusiones En los estudios multicéntricos clínicos la protocolización centralizada de los datos por un data-manager parece presentar resultados similares a la protocolización directa en la base de datos en el centro de origen. (AU)

Introduction In multicenter studies, the protocolization of data is a critical phase that can generate biases. The objective is to analyze the concordance and reliability of the data obtained in a clinical multicenter study between the protocolization in the center of origin and the centralized protocolization of the data by a data-manager. Methods National multicenter clinical study about an infrequent carcinoma. A double protocolization of the data is carried out: (i)center of origin; and (ii)centralized by a data manager. The concordance between the data is analyzed for the global data and for the two groups of the project: (i)study group (familiar carcinoma, 30 researchers protocolize); (ii)control group (sporadic carcinoma, 4 people protocolize). Interobserver variability is evaluated using Cohen's kappa coefficient. Results The study includes a total of 689 patients with carcinoma: 252 in the study group and 437 in the control group. Regarding the concordance analysis of the tumor stage, 2.5% of disagreements were observed and the concordance between people who protocolize was near perfect (Kappa=0.931). Regarding the evaluation of the recurrence risk, disagreements occurred in 7% of the cases and the concordance was near perfect (Kappa=0.819). Regarding the sonography evaluation (TIRADS), the disagreements were 6.9% and the concordance was near perfect (Kappa=0.922). Also, 4.6% of transcription errors were detected. Conclusions In multicenter clinical studies, the centralized data protocolization by a data-manager seems to present similar results to the direct protocolization in the database in the center of origin. (AU)

Diagnostic and prognostic impact of preoperative thrombocytosis in muscle invasive bladder cancer: Any role in clinical practice?

BACKGROUND: Since earlier research suggested a link between preoperative thrombocytosis and poor oncological outcomes in several cancers, the significance of platelet count abnormalities in bladder carcinoma (BC) demands for further investigation. OBJECTIVE: To assess the prognostic value of preoperative thrombocytosis (PTC) on survival in patients with bladder carcinoma treated by radical cystectomy (RC). PATIENTS AND METHODS: Analytical cohort comprised a single-center series of 299 patients who underwent RC for bladder carcinoma was evaluated. A platelet count beyond the threshold of 400 × 109 /L was considered thrombocytosis. Along with the Kaplan-Meier survival probability, cox proportional hazard regression models were used. RESULTS: Twenty-eight (9.4%) patients had preoperative thrombocytosis. PTC was associated with gender, tumor stage, tumor grade, lymphovascular invasion, hydronephrosis, anemia (p < 0.001), and hypoalbuminemia (p < 0.001). Preoperative thrombocytosis was strongly linked to worse overall survival (OS) (p = 0.002), and cancer specific survival (CSS) (p = 0.004), according to the Kaplan-Meier method. Throughout the follow-up, a total of 198 (66.2%) patients died, including 170 (56.9%) from BC. For this study population 5-year CSS was 45.8%. Preoperative thrombocytosis was not independently associated with OS (HR 1.168; 95% CI 0.740-1.844; p = 0.504) or CSS (HR 1.060; 95% CI 0.649-1.730; p = 0.816) in multivariate Cox regression analysis. Only tumor stage (HR 2.558; 95% CI 1.675-3.908; p < 0.001), hydronephrosis (HR 1.614; 95% CI 1.173-2.221; p = 0.003), lymph node metastasis (HR 1.555; 95% CI 1.076-2-2.248; p = 0.019), anemia (HR 1.454; 95% CI 1.034-2.046; p = 0.032) and ASA grade (HR 1.375; 95% CI 1.006-1.879; p = 0.046) were independently associated with CSS. CONCLUSIONS: In a single-center study of consecutive patients who underwent radical cystectomy for bladder cancer, preoperative thrombocytosis was unable to predict outcomes.

Tractography Navigated Endoscopic En-Bloc Excision of Pediatric Giant Choroid Plexus Tumor.

Giant choroid plexus (CP) tumors in children pose a formidable surgical challenge due to extensive vascularity/blood loss, tumor size impeding early visualization of the pedicle, hydrocephalus/mass effect distorting cerebral localization, considerable prevalence of atypical tumors and carcinoma demanding excision without tumor spillage, and retraction-associated morbidity. However, total resection of CP papilloma has excellent potential for cure. This is probably the first report in the literature of diffusion tensor imaging navigation-guided tumor pedicle targeting, endoscopic devascularization and division of pedicle followed by en bloc delivery in optimally tackling most of these challenges in a 6-year-old girl presenting with a giant lateral ventricular CP tumor. Giant CP tumors pose a formidable challenge. Extensive vascularity can cause life-threatening blood loss in children.1 Large tumor size makes it impractical during microsurgery to achieve early visualization of pedicle.2 Hydrocephalus and mass effect can distort sulcal anatomy, with potentially devastating deficits.3 Still, prevalence of atypical tumors and carcinoma warrants excision without tumor spillage.4 In Video 1, we demonstrate our "10-D" steps of en-bloc excision, exploiting panoramic visualization of endoscope5: 1. Diagnosis, 2. Diffusion tensor imaging guided pedicle targeting, 3. Design position & exposure, 4. Durotomy, 5. Dissection of sulcus, 6. Delineation of pedicle, 7. Devascularization, 8. Division of pedicle, 9. Delivery of tumor, and 10. Dural & skin closure. The conventional superior parietal lobule approach to get the tumor en-bloc would have been from the posterosuperior direction, where the tumor is likely to conceal the pedicle. The trajectory to first get to the pedicle must be from an anterosuperior direction but will violate corticospinal fibers. Hence entry point was chosen in between, just posterior to the post-central sulcus. To accommodate the 'en-bloc' excision avoiding ventricular seedlings, a 5 cm mini-craniotomy was fashioned centered on the entry point planned in the navigation system. Ventricle was entered perpendicular to the sulcus through the roof of the atrium, with least cortical transgression and avoiding injury to laterally placed optic radiation and speech areas.6 A 30-degree, 4-mm endoscope was inserted anterolateral to the tumor and fixed. The wide-angled vision offered by endoscopes enhancing meticulous dissection is the likely cause of better neurological outcomes, as noted in other ventricular lesions.7 Pedicular attachment of the tumor is coagulated thoroughly and cut, ensuring initial sparing of venous drainage. The draining vein is then coagulated and divided. 'En-bloc' excision is also known in other vascular lesions to decrease the risk of bleeding.8 The angled optics & panoramic visualization helps to identify any possible tumor seedlings.9 This is probably the first report of endoscopic en-bloc excision of a giant choroid plexus tumor in literature.

New progress of tuberculosis scar carcinoma.

It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).

Streptococcus Mitis Endocarditis Associated with Early Gastric Carcinoma.

We report a case of Streptococcus mitis endocarditis associated with early gastric carcinoma. A 71-year-old man who had been diagnosed with aortic regurgitation (AR) two years previously was referred for valve surgery and evaluation of elevated inflammatory markers. Four months previously, atrophic gastritis, early gastric adenocarcinoma, and colon polyp had been identified in the patient during endoscopy. However, Helicobacter pylori testing was negative. On admission, he had no dental diseases or recent oral procedures. Echocardiography demonstrated severe AR and mobile vegetation on the aortic valve. Magnetic resonance imaging revealed cerebral embolism and spondylodiscitis. Blood cultures grew Streptococcus mitis. At surgery, destruction of the left cusp with vegetation and a perforation of the non-coronary cusp were found; in addition, aortic valve replacement was performed. Although the association between Streptococcus bovis bacteremia and colon neoplasm is well recognized, the association between Streptococcus mitis endocarditis and gastrointestinal carcinoma should also be kept in mind.

Radiobiological modeling of radiation-induced acute proctitis: A single-institutional study of prostate carcinoma.

Purpose: To estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute proctitis in prostate cancer patients treated with intensity modulated radiation therapy (IMRT) for the calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five prostate cancer patients were enrolled and evaluated weekly for acute radiation-induced (ARI) proctitis toxicity. Their scoring was performed as per common terminology criteria for adverse events version 5.0. The radiobiological parameters namely n, m, TD50, and γ50 were calculated from the fitted SDR curve obtained from the clinical data of prostate cancer patients. Results: ARI toxicity for rectum in carcinoma of prostate patients was calculated for the endpoint of acute proctitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade 1 and Grade 2 acute proctitis are found to be 0.13, 0.10, 30.48 ± 1.52 (confidence interval [CI] 95%), 3.18 and 0.08, 0.10, 44.37 ± 2.21 (CI 95%), 4.76 respectively. Conclusion: This study presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 ARI rectum toxicity for the endpoint of acute proctitis. The provided nomograms of volume versus complication and dose versus complication for different grades of acute proctitis in the rectum help radiation oncologists to decide the limiting dose to reduce the acute toxicities.

Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma.

BACKGROUND/AIM: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. MATERIALS AND METHODS: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. RESULTS: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. CONCLUSION: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.

Thrombotic microangiopathy and disseminated intravascular coagulation in a patient with carcinomatosis of the bone marrow due to gastric adenocarcinoma: Case report.

Carcinomatosis of the bone marrow is a rare clinical condition characterized by diffuse tumor infiltration of the bone marrow accompanied by hematological abnormalities, including thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). In patients with gastric carcinoma, this association is infrequent. Below we present a case of a 19-year-old female patient with no known pathological history who presented with upper digestive tract bleeding. Upon examination, anemia and thrombocytopenia were documented, with schistocytes in the peripheral blood smear and prolonged coagulation times. Endoscopic studies indicated a lesion in the Borrmann IV gastric body, and the bone marrow biopsy showed the presence of signet ring cells. Because there was no possibility of systemic therapy, the patient died during hospitalization. This case contributes to the medical literature by describing an unusual presentation of a very frequent pathology.

[Ulcerative colitis-associated carcinogenesis : An update]. / Colitis-ulcerosa-assoziierte Karzinogenese : Ein Update.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease beginning in the rectum and gradually extending to the right-sided colon and the terminal ileum (backwash-ileitis). Its causes are still not completely understood. Genetic susceptibility, changes in the microbiota and immune response, as well as environmental factors are thought to influence the disease course.Patients with UC are at increased risk of developing colorectal cancer (CRC) when compared to an age-matched normal population. Cancer risk increases with early onset, duration, and extent of the disease, with development of strictures, intraepithelial neoplasia, and concomitant primary sclerosing cholangitis.In contrast to the sporadic adenoma-carcinoma-sequence, UC-related CRC develops through an inflammation-intraepithelial neoplasia-carcinoma-sequence, in which genetic alterations already occur in the inflamed epithelium before the development of intraepithelial neoplasia.This article summarizes the current state of knowledge regarding UC-related carcinogenesis and its possible impact on prevention and therapy.

Using immunohistochemistry to classify the molecular subtypes of Paget's disease of the breast.

PURPOSE: To classify the molecular subtypes of Paget's disease of the breast, and then compare them with general breast cancer to get deeper understanding of this disease and offer better management of associate patients in clinical decisions. METHODS: We used immunohistochemistry to examine 42 cases of this disease by antibodies against estrogen and progesterone receptors, Ki-67, as well as human epidermal growth factor receptor 2 (HER-2). Due to damage and loss of specimens, etc., we obtained 36 pathological specimens from the 42 patients. For 30 of 36 pathological specimens (83.3%), we obtained a complete molecular subtype. Cause the other 6 pathological specimens have missing immunohistochemistry items. For patients with bilateral breast cancer, only information on the side with PDB is listed. For patients with recurrence, only information on the first onset was included. We finally compared and studied the molecular subtype of 26 samples. We calculated the relative frequencies of molecular subtypes including luminal A, luminal B, HER-2-enriched, and basal-like and compared them between PDB and general breast carcinomas in other studies. RESULTS: The luminal A and B subtype were found, respectively, in 3 (11.5%) and 6 (23.1%) of all patients, and 15 cases of HER-2-enriched subtype was detected (57.7%). In addition, 2 (7.7%) showed a basal-like subtype. CONCLUSION: The molecular subtypes of common breast cancer and PDB-associated breast cancer differ. Luminal subtypes are the most common in the former, while within our samples HER-2 positive subtype was the highest in PDB-associated breast carcinoma. With further understanding of this disease, rational therapies will be applied in different patients and cures for PDB and PDB-associated carcinoma will be achieved.

The contribution of PET/CT to the differentiation of benign and malignant pleural effusion in patients with ovarian carcinoma.

OBJECTIVE: The present study investigates the ability of non-invasive contribution of positron emission tomography (PET)/computed tomography (CT) to distinguish between benign pleural effusions (BPE) and malignant pleural effusions (MPE) in patients diagnosed with ovarian carcinoma (OC). MATERIAL AND METHODS: Included in the study were 32 OC patients with a PE diagnosis. The cases with BPE and MPE were compared in terms of the PE maximum standardized uptake value (SUVmax), PE SUVmax/mean standardized uptake (SUVmean) value of the mediastinal blood pool (TBRp), the presence of pleural thickening, the presence of supradiaphragmatic lymph node, unilateral or bilateral PE, pleural effusion diameter, patient age and CA125 value. RESULTS: The mean age of the 32 patients was 57±2.8 years. TBRp>1.1, pleural thickening and supradiaphragmatic lymph node were observed significantly more frequently in the MPE than the BPE cases. While no pleural nodules were detected in patients with BPE, they were present in 7 of the patients with MPE. The rates of distinction between the MPE and BPE cases were as follows: the sensitivity of the TBRp value was 95.2% and specificity was 72.7%; the sensitivity of pleural thickness was 80.9% and specificity was 81.8%; the sensitivity of supradiaphragmatic lymph node was 38% and specificity was 90.9%; and the sensitivity of the pleural nodule was 33.3% and specificity was 100%. There were no significant differences between two groups in any other factors. CONCLUSIONS: Pleural thickening and TBRp values ascertained through PET/CT may aid the distinction between MPE-BPE, especially in patients with advanced stage OC with a poor general condition, or those who cannot undergo surgery.