Urinary miRNAs Predict Metastasis in Patients With Clinically Localized Clear Cell Renal Cell Carcinoma Treated With Nephrectomy.

PURPOSE: Patients with clear cell renal cell carcinoma (ccRCC) might develop metastasis after surgery with curative intent. We aimed to characterize the expression levels of microRNAs in the urine (UmiRNAs) of patients before and after nephrectomy to determine the impact of UmiRNAs expression in the emergence of metastases. METHODS: We prospectively collected pre- and post-nephrectomy urine samples from 117 patients with clinically localized and locally advanced ccRCC. UmiRNAs were extracted, purified, and measured using RT-PCR. Relative quantifications (RQ) of 137 UmiRNAs were calculated through 2-∆∆ method. The post-surgery/pre-surgery RQs ratio represented the magnitude of the expression levels of the UmiRNAs. The association of UmiRNA expression and the development of distant metastases was tested with Cox regression model. RESULTS: Five UmiRNAs (miR-191-5p, miR-324-3p, miR-186-5p, miR-93-5p, miR-30b-5p) levels were upregulated before nephrectomy (p < .05). This conferred a 2- to 4-fold increased risk of metastasis, with miR-191-5p showing the most significant association with this endpoint (HR = 4.16, 95% CI = 1.38-12.58, p = .011). In a multivariate model stratified with stage and Fuhrman grade, we found that miR-191-5p, miR-324-3p, and miR-186-5p exhibited a strong association with metastasis development in patients with pathological T3 (pT3) tumors. Enrichment analysis with the most differentially expressed UmiRNAs showed that these UmiRNAs targeted genes that regulate cell survival and proliferation. CONCLUSION: Our study indicated UmiR-191-5p, UmiR-324-3p, and UmiR-186-5p are potential markers to predict the development of metastasis, particularly in pT3 patients. PATIENT SUMMARY: We compared changes of UmiRNAs expression detected pre- and postnephrectomy of patients with ccRCC. Our findings suggest that UmiRNA expression likely reflects tumor-specific changes that can be promising to predict the metastasis development, particularly in patients with non-metastatic locally advanced ccRCC. If confirmed, these findings may be useful for surveillance protocols for adjuvant therapy protocols.

Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival.

CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.

Impact of Surgical Resection of the Primary Tumor on Overall Survival in Patients With Metastatic Pheochromocytoma or Sympathetic Paraganglioma.

OBJECTIVE: To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS). BACKGROUND: Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known. METHODS: We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information. RESULTS: A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8-183.2 months vs 36 months, 95% CI 27.2-44.8 months; P < 0.001].Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5-105.4 months vs 36 months, 95% CI 29.7-42.3 months; P < 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P = 0.1798, two sample t test; P = 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rank P < 0.001).In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion. CONCLUSIONS: Primary tumor resection in patients with metastatic PPG appeared to be associated with improved OS. In patients with hormonally active tumors, surgical resection led to better blood pressure control.

Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. METHODS: Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %). RESULTS: Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15-57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses. CONCLUSION: In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin's association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract.

OBJECTIVE: To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes. RESULTS: Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53% muscle-invasive or greater (≥pT2), 74% high-grade, 16% with flat architecture, 13% with necrosis, 21% with lymphovascular invasion, 18% with concomitant carcinoma in situ, and 8% with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25%) experienced disease recurrence and 121 (21%) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95% CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95% CI: 1.02-1.18, P = .05). CONCLUSION: Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC.

Carcinoma mucoepidermoide bronquial: tumor raro en niños / Bronchial mucoepidermoid carcinoma: rare tumor in children

Introducción. Las neoplasias pulmonares son raras en niños. La tráquea y la vía aérea superior contienen glándulas mucosas y serosas similares a las de las glándulas salivales mayores. De estas glándulas surge un grupo de tumores, muy poco comunes, que incluye el carcinoma adenoideo quístico, el carcinoma mucoepidermoide, el adenoma pleomórfico, el carcinoma de células acinares y el oncocitoma. El carcinoma mucoepidermoide representa 0.2% de los casos de cáncer pulmonar a cualquier edad. A la fecha, en la literatura mundial se han reportado solamente alrededor de 100 niños con esta entidad. Antiguamente se clasificaban como adenomas bronquiales, término inapropiado para una neoplasia que, aunque de crecimiento lento, puede ser localmente invasiva. Presenta un curso relativamente benigno cuando corresponde a tumores de bajo grado de malignidad. Se manifiesta como neumonías recurrentes o de lenta resolución. La evaluación de estos pacientes debe ser exhaustiva. El tratamiento más aceptado es la resección quirúrgica del lóbulo pulmonar afectado, con los respectivos ganglios linfáticos hiliares lobares. Caso clínico. Paciente de sexo femenino de 10 años de edad, con historia de infecciones recurrentes de vías aéreas y dos veces neumonía en el pulmón izquierdo. Se realizó tomografía de tórax y se encontró estenosis del bronquio izquierdo, que se corroboró mediante un estudio endoscópico. Después de la neumonectomía, el estudio histológico y el inmunohistoquímico indicaron carcinoma mucoepidermoide de bajo grado. Conclusiones. El carcinoma mucoepidermoide de bajo grado de malignidad presenta buen pronóstico al realizarse su extirpación completa.

Background. Lung neoplasms are rare in children. Mucous and serous glands from trachea and upper airway contain similar cells to those of the major salivary glands. Of these glands there is a group of very rare tumors including adenoid cystic carcinoma, mucoepidermoid carcinoma, pleomorphic adenoma, acinic cell carcinoma and oncocytoma. Mucoepidermoid carcinomas represent 0.2% of cases of lung cancer at any age, and slightly more than 100 children have been reported with this entity in the world literature. Formerly classified as bronchial adenoma, this term is inappropriate for a slow-growing neoplasm and may be locally invasive. These tumors present a relatively benign course when they correspond to tumors of low-grade malignancy and may be manifested as recurrent pneumonia or slow resolution. Children with these clinical manifestations should be thoroughly evaluated including endoscopic and tomographic studies. Surgical resection of the affected lung lobe with the respective lobar hilar lymph nodes is the most accepted treatment. Case report. We report the case of a 10-year-old female with a history of recurrent airway infection and two left lung pneumonias. Chest tomography showed a left bronchus stenosis confirmed by endoscopy. Following pneumonectomy, the histopathological and immunohis-tochemical findings reported a low-grade mucoepidermoid carcinoma. Conclusions. Mucoepidermoid carcinoma of low-grade malignancy has a good prognosis with complete tumor excision that requires a comprehensive approach that includes bronchoscopy.

Massive infestation by Ascaris lumbricoides of the biliary tract: report of a successfully treated case

This is a report of a 25 years old black woman from the city of São Paulo, Brazil, who developed acute obstructive cholangitis of Ascaris lumbricoides with septicemia and multiple hepatic abscesses. The patient had sickle cell trait and normal delivery 3 months ago. Massive infestation of the biliary tract by Ascaris lumbricoides was diagnosed by abdominal ultrasonography and endoscopic retrograde cholangiography. Sixty worms were removed from the common bile duct and hepatic abscesses were drained by surgery. The infectious process was polymicrobial. The patient's recovery was complete after a long evolution with a wide spectrum antibiotic therapy. New surgeries were needed to remove residual worms in the biliary tract. The diagnostic methods, clinical-biochemical features and also the clinical and surgical management are presented. The biliary ascariasis pathophysiology is commented.