Analysis of the Clinicopathological Characteristics and Prognosis of Patients with Nonurothelial Bladder Cancer

Background: Due to the low incidence of nonurothelial bladder cancer (NUBC), there is limited evidence in the field of evidence-based medicine regarding treatment modalities for such diseases. The purpose of our study was to explore the clinicopathological characteristics and prognostic factors of NUBC. Methods: We retrospectively analyzed the clinical data of 135 bladder squamous cell carcinoma (SqCC) and adenocarcinoma (AC) patients treated at the Second Hospital of Tianjin Medical University between October 2011 and February 2022, including 70 SqCC and 65 AC patients; We also analyzed 145 patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2011 to 2020, including 108 SqCC and 37 AC patients. Clinicopathological characteristics and prognoses were compared between the SqCC and AC groups. Additionally, the Kaplan‒Meier method and log-rank tests were used to perform survival analysis, and the Cox proportional hazard model was applied to analyze clinical factors affecting prognosis. Results: Comparisons of clinicopathological characteristics between the SqCC and AC groups revealed that age at diagnosis (p < 0.001, p < 0.001), tumor diameter (p < 0.001), tumor location (p = 0.002), and surgical approach (p < 0.001) were significantly different. Univariate and multivariate Cox regression analyses indicated that lymph node metastasis (p = 0.031), advanced pT stage (p < 0.001), and SqCC (p < 0.001) were independent risk factors affecting the prognosis of NUBC patients, and comparisons of clinicopathological characteristics between the SqCC and AC groups from the SEER database revealed that tumor diameter (p < 0.001), tumor location (p = 0.033), tumor number (p = 0.004), surgical approach (p = 0.005), and lymph node metastasis (p = 0.017) were statistically significant... (AU)

Bone metastatic cancer of unknown primary at initial presentation

Introduction Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. Methods From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. Results Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. Discussion Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results (AU)

Which is the appropriate surgical procedure for appendiceal adenocarcinoma: appendectomy, partial colectomy or right hemicolectomy?

Objective The purpose of this study was to explore the appropriate surgical procedure and clinical decision for appendiceal adenocarcinoma. Methods A total of 1,984 appendiceal adenocarcinoma patients from 2004 to 2015 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into three groups based on the extent of surgical resection: appendectomy (N = 335), partial colectomy (N = 390) and right hemicolectomy (N = 1,259). The clinicopathological features and survival outcomes of three groups were compared, and independent prognostic factors were assessed. Results The 5-year OS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 58.3%, 65.5% and 69.1%, respectively (right hemicolectomy vs appendectomy, P < 0.001; right hemicolectomy vs partial colectomy, P = 0.285; partial colectomy vs appendectomy, P = 0.045). The 5-year CSS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 73.2%, 77.0% and 78.7%, respectively (right hemicolectomy vs appendectomy, P = 0.046; right hemicolectomy vs partial colectomy, P = 0.545; partial colectomy vs appendectomy, P = 0.246). The subgroup analysis based on the pathological TNM stage indicated that there was no survival difference amongst three surgical procedures for stage I patients (5-year CSS rate: 90.8%, 93.9% and 98.1%, respectively). The prognosis of patients who underwent an appendectomy was poorer than that of those who underwent partial colectomy (5-year OS rate: 53.5% vs 67.1%, P = 0.005; 5-year CSS rate: 65.2% vs 78.7%, P = 0.003) or right hemicolectomy (5-year OS rate: 74.2% vs 53.23%, P < 0.001; 5-year CSS rate: 65.2% vs 82.5%, P < 0.001) for stage II disease. Right hemicolectomy did not show a survival advantage over partial colectomy for stage II (5-year CSS, P = 0.255) and stage III (5-year CSS, P = 0.846) appendiceal adenocarcinoma (AU)

Percutaneous cholecystostomy: an unusual route of dissemination of gallbladder carcinoma

A 78-year-old male with high-risk surgical presented severe acute cholecystitis and required cholecystostomy. The patient was referred later for assessment of the surgical treatment. A cholangio-MRI revealed a lesion on the gallbladder fundus with hepatic lesions suggestive of metastatic gallbladder carcinoma, which was confirmed in the histological analysis. The tumor progressed despite the chemotherapy through the cholecystostomy tract and developed peritoneal carcinomatosis. The patient did not respond to chemotherapy and he died 12 months later. (AU)

Resección venosa en cirugía oncológica pancreática: opciones técnicas ante situaciones diversas / Venous resection in pancreatic oncologic surgery: Different techniques for different situations

Introducción: Análisis de los resultados de resección venosa en cirugía pancreática oncológica de 2 centros de referencia. Se analiza el tipo de intervención realizada, los tipos de reconstrucción vascular, el estudio anatomopatológico, la morbimortalidad postoperatoria y la supervivencia a 3 y 5 años. Métodos: Análisis retrospectivo, transversal y comparativo. Se incluyen 41 pacientes intervenidos de lesiones neoplásicas pancreáticas desde 2003 hasta 2021 que requirieron resección venosa por afectación vascular. Resultados: La técnica quirúrgica más frecuente fue la duodenopancreatectomía cefálica tipo Whipple, realizada en 35 de los 41 pacientes (85%). Uno de los casos se realizó por acceso laparoscópico. La reconstrucción vascular tipo 1 (sutura simple) se realizó en 11 pacientes (27%), la tipo 2 (patch de falciforme) en 4 casos (10%), la tipo 3 (sutura término-terminal) en 23 casos (56%) y la reconstrucción tipo 4 (injerto autógeno) en 3 casos (7%). La longitud media del segmento venoso resecado fue de 21mm (11-46) y el tiempo quirúrgico medio fue de 290min (220-360). El 90% (37/41) fueron adenocarcinoma de páncreas. El 83% se consideraron R0 y hubo afectación en el tramo vascular resecado en el 41% de los casos. Hubo morbilidad Clavien-Dindo>3 en 4 pacientes y no hubo ningún caso de mortalidad postoperatoria. La supervivencia a 3 años fue del 48% y a 5 años del 20%. Conclusiones: La resección venosa con reconstrucción para asegurar una resección R0 es una técnica factible, con una aceptable tasa de morbimortalidad y supervivencia global. (AU)

Introduction: To report the clinical results of patients with malignant pancreatic lesions who underwent oncological surgery with vascular resection. The type of intervention performed, the types of vascular reconstruction, the pathological anatomy results, postoperative morbidity and mortality, and survival at 3 and 5 years were analysed. Methods: Retrospective, cross-sectional and comparative analysis. We include 41 patients with malignant pancreatic lesions who underwent surgery with vascular resection due to vascular involvement, from 2013 to 2021. Results: The most performed surgery was the cephalic pancreaticoduodenectomy (Whipple procedure) using median laparotomy, in 35 of the 41 patients (85%). One of the cases in the series was performed laparoscopically. Type 1 reconstruction (simple suture) was performed in 11 (27%) patients, type 2 in 4 (10%) cases, type 3 (T–T suture) in 23 (56%) cases, and type 4 reconstruction by autologous graft in 3 (7%) cases. The mean length of the resected venous segment was 21 (11–46)mm and the mean surgical time was 290 (220–360)min. 90% (37/41) were pancreatic adenocarcinoma. 83% were considered R0 and there was involvement in the resected vascular section in 41% of the cases. Four patients had Clavien-Dindo morbidity>3 and there were no cases of postoperative mortality. Survival at 3 years was 48% and at 5 years was 20%. Conclusions: The aggressive surgical treatment with venous resection in pancreatic malignant lesions to ensure R0 and its vascular reconstruction is a feasible technique, with an acceptable morbid-mortality rate and overall survival. (AU)

Un reto multidisciplinar: tratamiento con fósforo-32 en el carcinoma de páncreas localmente avanzado / A multidisciplinary challenge: Therapy with phosphorus-32 for locally advanced pancreatic cancer

El cáncer de páncreas es una enfermedad de pronóstico precario, siendo su supervivencia global la que menos ha mejorado en los últimos 40 años entre todos los cánceres. El adenocarcinoma de páncreas localmente avanzado, sin metástasis a distancia, pero con una afectación vascular limitante, constituye casi un tercio de estos pacientes. En este grupo se concentran gran parte de los esfuerzos investigadores para introducir tratamientos que permitan un aumento de las tasas de rescate quirúrgico y/o de la supervivencia, con 2 objetivos fundamentales: el del control local y el de la prevención de la progresión sistémica. El tratamiento intratumoral con micropartículas de fósforo-32, guiado por ecoendoscopia y combinado con quimioterapia estándar puede tener beneficios significativos y clínicamente relevantes en estos pacientes y, por tanto, una opción valiosa de tratamiento en una enfermedad en la que existe una necesidad urgente de desarrollar nuevas terapias que nos ayuden a mejorar los resultados (AU)

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes (AU)

Comprehensive analysis and identification of prognostic biomarkers and immunotherapeutic targets in the NADPH oxidase family (and its regulatory subunits) in pancreatic ductal adenocarcinoma

Purpose This study aimed to evaluate the role of NADPH in pancreatic ductal adenocarcinoma using bioinformatic analyses and experimental validations. Methods We compared the expression levels, performed GO and KEGG analysis of NADPH oxidase family and its regulatory subunits, and determined the survival of patients with pancreatic ductal adenocarcinoma by GEPIA, David and KM plotter. The relationship between their expression with immune infiltration levels, phagocytotic/NK cell immune checkpoints, recruitment-related molecules were detected by Timer 2.0 and TISIDB, respectively. Subsequently, their correlation with NK cell infiltration level was verified by immunohistochemistry. Results The expression of some members of the NADPH oxidase family and its regulatory subunits was significantly increased in pancreatic ductal adenocarcinoma tissues compared to that in normal tissues and was positively correlated with natural killer (NK) cell infiltration. Furthermore, the NADPH oxidase family and its regulatory subunits were associated with survival and immune status in patients with pancreatic ductal adenocarcinoma, including chemokines, immune checkpoints, and immune infiltration levels of NK cells, monocytes, and myeloid-derived suppressor cells. Conclusions These results suggest the NADPH oxidase family and its regulatory subunits might serve as indicators for predicting the responsiveness to immunotherapy and outcome of patients with pancreatic ductal adenocarcinoma, providing a new perspective or strategy for immunotherapy in pancreatic ductal adenocarcinoma (AU)

Low-grade dysplasia in Barrett's esophagus: A problematic diagnosis / Displasia de bajo grado en el esófago de Barrett: un diagnóstico problemático

Although low-grade dysplasia (LGD) in Barrett's esophagus (BE) is a histopathological diagnosis based on different histological abnormalities, it is still problematic for different reasons. Patients without confirmed diagnosis of LGD undergo unnecessary and intensified follow-up where the risk of progression is low in the majority of cases. In contrast, the presence of confirmed LGD indicates a high risk of progression. In this article we try to address these reasons focusing on re-confirmation of LGD diagnosis, interobserver agreement, and persistent confirmed LGD. The progression risk of LGD to high-grade dysplasia and esophageal adenocarcinoma will also be reviewed. (AU)

Aunque la displasia de bajo grado (DBG) en el esófago de Barrett (EB) es un diagnóstico histopatológico basado en diferentes anomalías histológicas, este no deja de ser problemático por diferentes razones. Los pacientes sin diagnóstico confirmado de DBG se someten a un seguimiento innecesario e intensificado donde el riesgo de progresión es bajo en la mayoría de los casos. Por el contrario, la presencia de DBG confirmada indica un alto riesgo de progresión. En este artículo tratamos de abordar estas razones centrándonos en la reconfirmación del diagnóstico de la DBG, la concordancia entre observadores y la DBG confirmada y persistente. También se revisará el riesgo de progresión de la DBG a displasia de alto grado y adenocarcinoma esofágico. (AU)

Evaluation of trefoil factor 3 as a non-invasive biomarker of gastric intestinal metaplasia and gastric cancer in a high-risk population / Evaluación de Trefoil factor 3 como un biomarcador no invasivo para la detección de metaplasia intestinal y cáncer gástrico en una población de alto riesgo

Background: Adenocarcinoma is preceded by chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Trefoil factor 3 (TFF3) is a peptide secreted by goblet cells, which is abundantly present in intestinal metaplasia. Aim: To evaluate the utility of serum TFF3 as a non-invasive biomarker for the diagnosis of intestinal metaplasia and gastric cancer. Methods: Single-center, cross-sectional study of 274 patients who consecutively underwent upper gastrointestinal endoscopy with gastric biopsies (updated Sydney system). TFF3 levels were measured in serum by a commercial ELISA kit. Patients with normal histology or chronic atrophic gastritis without intestinal metaplasia comprised the control group. In addition, 14 patients with invasive gastric cancer were included as a reference group. The association between TFF3 levels and intestinal metaplasia was assessed by logistic regression. Results: Patients with intestinal metaplasia (n=110) had a higher median TFF3 level as compared to controls (n=164), 13.1 vs. 11.9ng/mL, respectively (p=0.024). Multivariable logistic regression showed a no significant association between TFF3 levels and intestinal metaplasia (OR=1.20; 95%CI: 0.87–1.65; p-trend=0.273). The gastric cancer group had a median TFF3 level of 20.5ng/mL, and a significant association was found (OR=3.26; 95%CI: 1.29–8.27; p-trend=0.013). Conclusion: Serum levels of TFF3 do not discriminate intestinal metaplasia in this high-risk Latin American population. Nevertheless, we confirmed an association between TFF3 levels and invasive gastric cancer.(AU)

Introducción: El adenocarcinoma gástrico es precedido por la gastritis crónica atrófica, metaplasia intestinal y displasia gástrica. Trefoil factor 3 (TFF3) es un péptido secretado por las células caliciformes, que están abundantemente presentes en la metaplasia intestinal. Objetivo: Evaluar la utilidad de TFF3 sérico como biomarcador no invasivo para el diagnóstico de metaplasia intestinal y cáncer gástrico. Métodos: Estudio transversal, de 274 pacientes a los que se les realizó endoscopia digestiva alta consecutivamente con biopsias gástricas (sistema Sydney actualizado). Los niveles de TFF3 se midieron en suero mediante un kit de ELISA comercial. Los pacientes con histología normal o gastritis crónica atrófica sin metaplasia intestinal formaron el grupo control. Además, se incluyeron como grupo de referencia 14 pacientes con cáncer gástrico avanzado. La asociación entre los niveles de TFF3 y la metaplasia intestinal se evaluó mediante una regresión logística. Resultados: Los pacientes con metaplasia intestinal (n=110) presentaron una mediana de TFF3 más alta en comparación con el grupo control (n=164), 13,1 vs. 11,9ng/ml, respectivamente (p=0,024). Sin embargo, la regresión logística multivariable no mostró una asociación significativa entre los niveles de TFF3 y la metaplasia intestinal (OR=1,20; IC95%: 0,87-1,65; p-trend=0,273). El grupo de cáncer gástrico tuvo una mediana significativamente mayor de TFF3 de 20,5ng/ml (OR=3,26; IC95%: 1,29-8,27; p-trend=0,013). Conclusión: Los niveles séricos de TFF3 no permiten el diagnóstico no invasivo de metaplasia intestinal en esta población latinoamericana de alto riesgo. La asociación entre los niveles de TFF3 y el cáncer gástrico avanzado fue confirmada.(AU)

ENO1 promotes immunosuppression and tumor growth in pancreatic cancer

Background Pancreatic adenocarcinoma (PAAD) is a highly aggressive and malignant cancer type with the highest mortality rate of all major cancers. However, the molecular and tumor immune escape mechanism underlying pancreatic cancer remains largely unclear. α-enolase (ENO1) is a glycolytic enzyme reported to overexpress in a variety of cancer types. This study was undertaken to investigate the functional role and therapeutic potential of ENO1 in pancreatic cancer. Methods We examined the expression levels of ENO1 across a broad spectrum of cancer types from the TCGA database. ENO1-knockout (ENO1-KO) through CRISPR/CAS9 technology in a mouse pancreatic cancer cell line (PAN02) was used to analyze the role of ENO1 on proliferation and colony formation. Flow cytometry and RT-PCR were also applied to analyze T lymphocytes and relevant cytokines. Results In the present study, we identified that ENO1 promoted pancreatic cancer cell proliferation. Our bioinformatics data indicated that ENO1 was significantly overexpressed in pancreatic cancer cell lines and tissues. Survival analyses revealed that ENO1 overexpression implicated poor survival of PAAD patients. Knockout of ENO1 expression repressed the ability of proliferation and colony formation in PAN02. In addition, ENO1-KO significantly decreased tumor growth in mouse models. Further flow cytometry and RT-PCR analysis revealed that ENO1-KO modulates the tumor microenvironment (TME), especially in suppressed Treg cells and inducing anti-tumor cytokine responses. Conclusions Taken together, our data showed that ENO1 was an oncogenic biomarker and might serve as a promising target for immunotherapy of pancreatic cancer (AU)

Niveles séricos de IGF-1 e IGFBP-3 en pacientes con esófago de Barrett y adenocarcinoma de esófago. Estudio longitudinal / Serological levels of IGF-1 and IGFBP-3 in patients with Barrett's esophagus and esophageal adenocarcinoma: Longitudinal study

Antecedentes: El esófago de Barrett (EB) es una entidad con una progresión histológica a malignidad conocida. Los factores de crecimiento insulínico (IGF, de insulin-like growth factor) están involucrados en la carcinogénesis asociada a la obesidad y se han asociado con el riesgo de padecer algunos tipos de cáncer. Objetivos: Evaluar los niveles serológicos de IGF-1 e IGFBP-3 en pacientes con EB y adenocarcinoma de esófago. Pacientes y métodos: Estudio prospectivo de pacientes con EB y adenocarcinoma de esófago explorados con gastroscopia entre septiembre 2012 y diciembre 2015 a los que se realizó una extracción de sangre para la determinación de IGF-1 e IGFBP-3. Se incluyó un grupo control. Resultados: Se incluyeron 116 pacientes: 36 controles, 62 con EB (42 sin displasia y 20 con displasia) y 18 con adenocarcinoma. El IGF-1 y la ratio molar IGF-1/IGFBP-3 presentaron un aumento progresivo en los grupos con EB y adenocarcinoma comparado con los controles (IGF-1: 135,55±66,07ng/ml; 148,33±81,5ng/ml; 108,19±46,69ng/ml, respectivamente; p=0,049) (ratio molar: 0,23±0,91; 0,29±0,11; 0,19±0,06, respectivamente; p=0,001), sin diferencias entre los diferentes grados histológicos. Cincuenta y cuatro de los 65 pacientes con EB fueron seguidos durante una mediana de 58,50 meses (12-113) y 11 de ellos (20,4%) presentaron progresión a displasia de bajo grado (n=8) o displasia de alto grado/adenocarcinoma (n=3), sin encontrar diferencias en el sistema IGF comparado con los que no progresaron. Conclusiones: Los pacientes con EB y adenocarcinoma esofágico presentan cambios en el sistema IGF aunque los niveles de IGF-1 e IGFBP-3 no se correlacionan con la progresión histológica del EB.(AU)

Background: Barrett's esophagus (BE) is an entity with a known histological progression to malignancy. The insulin-like growth factor (IGF) system is involved in the carcinogenesis through obesity-related mechanisms that include IGF and it has been associated with several types of cancer. Objectives: To evaluate the serological levels of IGF-1 and IGFBP-3 in patients with BE and esophageal adenocarcinoma. Patients and methods: Prospective study of patients with BE and esophageal adenocarcinoma who underwent upper endoscopy between September 2012 and December 2015. A baseline determination of IGF-1 and IGFBP-3 was performed. We included a control group of patients without BE. Results: One hundred sixteen patients were included: 36 controls, 62 with BE (42 without dysplasia and 20 with dysplasia) and 18 with adenocarcinoma. IGF-1 and IGF-1/IGFBP-3 molar ratio showed a progression to high levels in BE and adenocarcinoma than in controls (IGF-1: 135.55±66.07ng/ml, 148.33±81.5ng/ml, 108.19±46.69ng/ml, respectively; P=.049) (molar ratio: 0.23±0.91, 0.29±0.11, 0.19±0.06, respectively; P=.001), without differences between the histological types of BE. Fifty-four out of the 65 patients with BE were followed up (median of 58.50 months, range 12–113) and 11 of them (20.4%) presented progression to low-grade dysplasia (n=8) or high-grade dysplasia/adenocarcinoma (n=3), without differences in the IGF system compared with patients without progression. Conclusions: Patients with BE and esophageal adenocarcinoma have changes in the IGF system although the serological levels of IGF-1 and IGFBP-3 do not correlate with histological progression of BE.(AU)

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response

Background: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. Objectives: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. Methods: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. Results: Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. Conclusions: This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD (AU)