Asociación entre metaplasia, displasia y cáncer de vesícula biliar en una EPS de Bogotá, Colombia / Association between metaplasia, dysplasia and gallbladder cancer in an EPS in Bogotá, Colombia

Introducción. El cáncer de vesícula biliar es el más común en el tracto biliopancreático y una importante causa de mortalidad. La metaplasia y la displasia han sido mencionados como probables precursores relacionados con la secuencia metaplasia-displasia-cáncer. El objetivo de este estudio fue establecer las posibles asociaciones entre estas alteraciones histopatológicas y su relación con la edad y el sexo de los pacientes. Métodos. Estudio observacional retrospectivo descriptivo, con un componente analítico de corte transversal. Se incluyeron los informes de patología de pacientes llevados a colecistectomía laparoscópica electiva y ambulatoria, entre enero de 2015 y diciembre de 2020, con colecistitis crónica, colelitiasis o pólipos vesiculares, mayores de 18 años. Se describieron las características demográficas por sexo y edad utilizando medias, desviaciones estándar y porcentajes. Se emplearon la prueba de chi cuadrado y la prueba exacta de Fisher para evaluar la asociación entre las variables cualitativas. Resultados. Se incluyeron 4871 informes de patología. En esta cohorte se encontró asociación estadísticamente significativa entre metaplasia, displasia y cáncer de vesícula (p<0,05), al igual que con el sexo y la edad de los pacientes. Conclusiones. Los resultados sugieren una asociación entre metaplasia, displasia y cáncer de vesícula biliar en la población estudiada. Se recomienda la realización de investigaciones complementarias para definir la posible causalidad entre metaplasia, displasia y cáncer de vesícula biliar en una población más heterogénea.

Introduction. Gallbladder cancer is the most common cancer in the biliopancreatic tract and an important cause of mortality. Metaplasia and dysplasia have been mentioned as probable precursors related to the metaplasia-dysplasia-cancer sequence. The objective of this study was to establish the possible associations between these histopathological alterations and their relationship with the age and sex of the patients. Methods. Descriptive retrospective observational study, with a cross-sectional analytical component. Pathology reports of patients undergoing elective and outpatient laparoscopic cholecystectomy were included between January 2015 and December 2020, with chronic cholecystitis, cholelithiasis, or gallbladder polyps, over 18 years of age. Demographic characteristics by sex and age was performed using means, standard deviations, and percentages. The chi2 test and Fisher's exact test were used to evaluate the association between the qualitative variables. Results. 4871 pathology reports were included. In this cohort, a statistically significant association was found between metaplasia, dysplasia, and gallbladder cancer (p<0.05), as well as with the sex and age of the patients. Conclusions. The results suggest an association between metaplasia, dysplasia and gallbladder cancer in the study population. Additional research is recommended to define the possible causality between metaplasia, dysplasia, and gallbladder cancer in a more heterogeneous population.

Giant adenoma of the gallbladder misdiagnosed as gallbladder carcinoma： A case report / 临床肝胆病杂志

One patient with gallbladder mass had transient jaundice and was diagnosed with gallbladder carcinoma by abdominal ultrasonography， contrast-enhanced CT， MRCP， and PET-CT. Surgical exploration showed enlarged gallbladder and a mass in the neck of the gallbladder pressing against the hilum of the liver， with no manifestation of tumor invasion， and there were no signs of liver metastasis. Only cholecystectomy was performed for the patient. The pathological diagnosis was tubular adenoma of the gallbladder without carcinogenesis. This case is characterized by a large gallbladder tumor， without marginal infiltration on imaging or malignant transformation based on pathology.

Clinical diagnosis， treatment， and prognosis of gallbladder sarcomatoid carcinoma： An analysis of 16 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. MethodsA retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. ResultsAmong the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ2=6.727， P=0.009）， surgical approach （χ2=7.508， P=0.006）， margin condition （χ2=7.934， P=0.005）， and adjuvant therapy （χ2=4.608， P=0.032） were associated with the prognosis of patients. ConclusionThe clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.

Recommendations from Annals of Surgical Oncology： Clinical guidelines for extrahepatic cholangiocarcinoma and gallbladder carcinoma / 临床肝胆病杂志

Biliary tract carcinoma （BTC） is a type of gastrointestinal tumor with a low incidence rate and a strong invasive ability， mainly including intrahepatic cholangiocarcinoma （ICC）， extrahepatic cholangiocarcinoma （ECC）， and gallbladder carcinoma （GC）， often accompanied by local progression or distant metastasis. Surgery is often the preferred treatment method for patients with local resectable tumor； however， there is still a high risk of recurrence after radical surgery. Therefore， multiple treatment modalities are often required for BTC patients， including surgical resection， systemic treatment （such as targeted therapy， chemotherapy， and immunotherapy）， and/or a combination of local treatment methods. With the development of the field of BTC， it is critical for surgical oncologists to understand and master the latest surgical strategies and the best patient selection and management systems. In view of the complexity of treatment and the continuous development of diagnosis and treatment techniques， Annals of Surgical Oncology， an authoritative American journal of cancer surgery， recently published the practical diagnosis and treatment guidelines for hepatobiliary tumors， including hepatocellular carcinoma （HCC）， ICC， ECC， and GC， aiming to provide more evidence-based evidence for the clinical management and decision-making of patients with hepatobiliary tumors. Due to the limitations of length and different emphases， this article mainly introduces the recommendations for the evaluation points and clinical treatment of ECC and GC in the guidelines， so as to provide a reference for clinical practice.

Gallbladder polyps: correlation and agreement between ultrasonographic and histopathological findings in a population with high incidence of gallbladder cancer / Pólipos da vesícula biliar: correlação e concordância entre achados ultrassonográficos e histopatológicos em uma população com alta incidência de câncer de vesícula biliar

ABSTRACT BACKGROUND: Gallbladder polyps are becoming a common finding in ultrasound. The management has to consider the potential risk of malignant lesions. AIMS: The aim of this study was to analyze the ultrasound findings in patients undergoing cholecystectomy due to gallbladder polyps and compare them for histopathological findings (HPs). METHODS: Patients with an ultrasonographic diagnosis of gallbladder polyp and who underwent cholecystectomy from 2007 to 2020 were included in the study. RESULTS: A total of 447 patients were included, of whom 58% were women. The mean age was 45±12 years. The mean size of polyps in US was 7.9±3.6 mm. Notably, 9% of polyps were greater than 10 mm, and single polyps were significantly larger than the multiple ones (p=0.003). Histopathological findings confirmed the presence of polyps in 88.4%, with a mean size of 4.8±3.4 mm. In all, 16 cases were neoplastic polyps (4.1%), 4 of them being malignancies, and all were single and larger than 10 mm. We found a significant correlation between ultrasound and histopathological findings polyp size determination (r=0.44; p<0.001). The Bland-Altman analysis obtained an overestimation of the US size of 3.26 mm. The receiver operating characteristic (ROC) curve analysis between both measures obtained an area under the receiver operating characteristic curve (AUC) of 0.77 (95%CI 0.74-0.81). Ultrasound polyps size larger than 10 mm had an odds ratio (OR) of 8.147 (95%CI 2.56-23.40) for the presence of adenoma and malignancy, with a likelihood ratio of 2.78. CONCLUSIONS: There is a positive correlation and appropriate diagnostic accuracy between ultrasound size of gallbladder polyps compared to histopathological records, with a trend to overestimate the size by about 3 mm. Neoplastic polyps are uncommon, and it correlates with size. Polyps larger than 10 mm were associated with adenoma and malignancy.

RESUMO RACIONAL: Os pólipos da vesícula biliar estão se tornando um achado comum na ultrassonografia (US). O manejo deve levar em consideração o risco de lesões malignas. OBJETIVOS: Analisar os achados da ultrassonografia em pacientes submetidos à colecistectomia por pólipos vesicais e compará-los com os achados histopatológicos. MÉTODOS: Foram revisados os prontuários médicos dos pacientes com diagnóstico ultrassonográfico de pólipo vesicular e submetidos à colecistectomia no período de 2007 a 2020. RESULTADOS: Foram incluídos no estudo 447 pacientes. A média de idade foi 45±12anos, sendo 58% mulheres. O tamanho médio dos pólipos na US foide 7,9±3,6mm. Nove por cento foram maiores que 10 mm, e os pólipos únicos encontrados foram maiores do que os múltiplos (p=0,003). A HP confirmou a presença de pólipos em 88,4%, tamanho médio 4,8±3,4mm. Dezesseis eram pólipos neoplásicos (4,1%) e quatro deles malignos, únicos e maiores que 10 mm. Foi encontrado correlação significativa entre a determinação do tamanho do pólipo ao ultrassonografia e histopatológicos (r=0,44; p<0,001). A análise de Bland-Altman obteve uma superestimação do tamanho do pólipo ao US em 3,26 mm. A análise da curva da característica de operação do receptor entre as duas medidas obteve uma área sob a curva curva da característica de operação do receptor (AUC) de 0,77 (IC95% 0,74-0,81). Pólipos ao ultrassonografia maiores que 10 mm apresentaram razão de chance (OR) de 8,147 (IC95% 2,56-23,40) para presença de adenoma e malignidade, com razão de verossimilhança de 2,78. CONCLUSÕES: Há uma correlação positiva e acurácia diagnóstica apropriada entre o tamanho dos pólipos da vesícula biliar por ultrassonografia em comparação com os achados histopatológicos, com uma tendência de superestimar o tamanho em cerca de 3 mm. Pólipos maiores que 10 mm foram associados a adenoma e malignidade.

Establishment and validation of prognosis prediction model for patients with gallbladder cancer based on albumin-bilirubin grade / 中华肝胆外科杂志

Objective:To establish and validate a prognosis prediction model of gall bladder cancer after surgery based on the albumin-bilirubin (ALBI) grade.Methods:The clinicopathological data of 161 patients with gallbladder cancer undergoing radical surgery in the First Hospital of Jiaxing between March 2011 to January 2020 were retrospectively analyzed, including 44 males and 117 females, aged (65±9) years old. The patients were grouped by the levels of ALBI score. The survival data were obtained through telephone or outpatient review. The Kaplan-Meier method was used to draw the survival curve. Multivariate analysis was performed using the Cox regression analysis model. The time-dependent receiver operating characteristic (ROC) curve was plotted to compare the prognostic value of the scoring system. A nomogram based on ALBI grade was established and its predictive performance was evaluated.Results:The 1, 3, 5 years overall survival (OS) rates of patients with gallbladder cancer were 76.7%, 52.5%, and 41.9%, respectively. The time-dependent ROC curves revealed that the area under the curve (AUC) values of ALBI grade were 0.659, 0.597 and 0.599 for 1, 2 and 3 years, showing a good prognostic performance. Multivariate regression analysis showed that poorer tumor differentiation ( HR=2.890, 95% CI: 1.816-4.600, P<0.001), TNM Ⅲ/Ⅳ stage ( HR=2.832, 95% CI: 1.781-4.503, P<0.001), ALBI grade 2 ( HR=1.595, 95% CI: 1.017-2.500, P=0.042), and ALBI grade 3 ( HR=3.938, 95% CI: 1.375-11.278, P=0.011) were independent risk factors for OS. The nomogram established with the independent risk factors such as ALBI grade showed a good predictive value for OS. The ROC curve results showed that the AUC values for 1, 3 and 5 years were 0.796, 0.806 and 0.799, respectively. The calibration plots and clinical decision curve analysis (DCA) showed the clinical feasibility of this nomogram. Conclusion:The nomogram model based on ALBI grading has a good predictive value for gallbladder cancer after surgery, which could guide the prognosis and individualized treatment decision-making.

Expression and clinical significance of miR-143 in gallbladder cancer / 中华肝胆外科杂志

Objective:This study aims to explore the expression of miR-143 in gallbladder cancer tissues and its correlation with tumor angiogenesis, clinicopathologic features and clinical prognosis.Methods:The clinical and pathological data of 78 patients with gallbladder cancer who were surgically resected and pathologically confirmed from January 2008 to June 2016 in the Department of General Surgery, Xuancheng Hospital Affiliated to Wannan Medical College were collected, including 20 males and 58 females, with an average age of (68.0±1.4) years. 78 cases of gallbladder cancer tissue were used as the tumor group, and 32 cases of normal gallbladder tissue adjacent to cancer were randomly selected as the control group. The expression level of miR-143 in the tumor group and the control group was detected by in situ hybridization. Microvessel density (MVD) were evaluated with immunohistochemistry to detect the expression of CD34 in tumor group. The expression of miR-143 and its correlation with tumor MVD, pathological characteristics and prognosis were analyzed by Cox regression analysis.Results:The results of in situ hybridization showed that the positive rate of miR-143 in gallbladder cancer tissues and average expression score were significantly lower than those in adjacent normal gallbladder tissues [29.49% (23/78) vs 62.5% (20/32), χ 2=10.39, P=0.001; (2.705±0.172) vs (4.688±0.405), t=5.33, P<0.001]. Correlation analysis showed that the expression of miR-143 was associated with lymph node metastasis of gallbladder cancer ( P=0.036). The MVD counts in the miR-143 positive group were significantly lower than those in the miR-143 negative group [(126.2±8.483) vs (157.4±6.412), t=2.75, P=0.007)]. The median survival time of gallbladder cancer patients with miR-143 positive and negative was 16 and 9 months, respectively. Cox regression analysis showed that the low expression of miR-143 was an independent risk factor affecting the clinical prognosis of gallbladder cancer. Conclusion:The expression of miR-143 is down-regulated in gallbladder cancer and participates in angiogenesis and clinical prognosis of gallbladder cancer.

Effects of neuropilin and tolloid-like 2 on proliferation, migration, cell cycle and apoptosis of gallbladder carcinoma cells and related mechanism / 中华肝胆外科杂志

Objective:To investigate the effects and molecular mechanism of neuropilin and tolloid-like 2 (NETO2) on proliferation, migration, cell cycle, and apoptosis in gallbladder cancer (GBC).Methods:The NETO2 mRNA and protein expression in GBC-SD, ZJU-0430, NOZ GBC cells were detected by quantitative real-time polymerase chain reaction and Western blot. NETO2 overexpression and knockdown stable cell lines were constructed by plasmid transfection. Cell counting kit-8 assay, colony formation assay, transwell assay, flow cytometry and WB assay were performed to evaluate proliferation, migration, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT) and changes of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway.Results:GBC-SD and ZJU-0430 cells with NETO2 gene overexpression and NOZ cells with NETO2 gene knockdown were effectively constructed. NETO2 overexpression in gallbladder cancer cell lines significantly improved cell proliferation and migration, advanced cell cycle progression from G0/G1 to S phase, and inhibited cell apoptosis. In the ZJU-0430 and GBC-SD cells, the clone number increased from (78.5±9.2), (217.0±6.4) to (213.5±10.3), (296.3±9.3)( t=10.98, 6.51; P=0.008, 0.023); The number of migrating cells increased from (198.6±8.4), (233.3±11.0) to (382.7±12.4), (379.0±7.3) ( t=16.98, 16.85, both P<0.001); The total apoptosis rate reduced from (29.7±0.9)%, (35.6±1.1)% to (19.2±0.5)%, (29.1±0.4)% ( t=9.74, 9.05; both P<0.001); The expression of EMT related proteins such as N-cadherin, Vimentin, Snail, and Slug were upregulated, while E-cadherin expression was downregulated. Phosphorylated PI3K (p-PI3K) and Akt (p-Akt) protein expression were significantly increased (all P<0.05). In contrast, NETO2 knockdown had the opposite effect on all these parameters. Conclusion:NETO2 influences the EMT process by regulating the PI3K/Akt signaling pathway, thus promotes GBC cell proliferation, migration and cell cycle progression, and inhibits cancer cell apoptosis.

Application of laparoscopic radical cholecystectomy in the treatment of stage Ⅲ gallbladder cancer / 中华肝胆外科杂志

Objective:To study the clinical efficacy of laparoscopic radical cholecystectomy in the treatment of stage Ⅲ gallbladder cancer.Methods:The clinical characteristics and postoperative follow-up data of 184 patients (male 66, and female 118) who underwent radical cholecystectomy for stage Ⅲ gallbladder cancer at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from May 2015 to May 2022, were retrospectively analyzed. The age was (67.0±8.6) years old (range 38 to 85 years old). There were 71 patients in the laparoscopic group and 113 in the open group. The general medical data, surgery-related indicators and complications were analyzed. Follow-up was completed by outpatient visits and by telephone.Results:The laparoscopic group showed better postoperative alanine aminotransferase [67.5 (40.0, 138.5) vs. 104.0 (45.0, 252.2) U/L] and aspartate aminotransferase [41.5 (26.0, 71.2) vs. 53.0 (30.2, 153.5) U/L] recovery, higher albumin levels [32.05 (30.18, 35.20) vs. 30.50 (27.70, 33.50) g/L], earlier abdominal drainage tube removal [8.00(6.00, 10.25) vs. 10.00(6.00, 13.00)d], shorter hospital stay [10.00(8.00, 15.25) vs. 14.00(9.00, 19.00) d] and lower incidences of complications [(14.1%(10/71) vs. 31.9%(36/113)] when compared with the open group (all P<0.05). The 1 year (49.1% vs 61.0%), 2 years (24.0% vs. 28.5%), 3 years (16.0% vs. 14.5%) overall survival ( P=0.640), and the 3 years progression-free survival (18.3% vs. 15.0%, P=0.463) showed no significant difference between the 2 groups. Conclusion:Laparoscopic surgery for AJCC TNM stage Ⅲ gallbladder cancer showed comparable results with open surgery. When compared with open surgery, laparoscopic radical resection of gallbladder cancer had the advantages of earlier removal of abdominal drainage tube, lower incidence of postoperative complications, and shorter hospital stay.

Effects of orlistat on the viability of human gallbladder cancer cells / 中华消化外科杂志

Objective:To investigate the effects of orlistat on the viability of human gall-bladder cancer (GBC) cells.Methods:The experimental study was conducted. The human GBC NOZ cells with high expression of FSAN was screened out through in vitro cultivating human GBC-SD, SGC-996 and NOZ cells. The cell proliferation assay, clone formation assay and protein detection experiment were used to analysis of the effects of orlistat on the viability of human GBC cells. Cell grouping: NOZ cells cultured with medium were set as the control group, cultured with medium + 10 μmol/L orlistat were set as the low-dose orlistat group, cultured with medium + 100 μmol/L orlistat were set as the high-dose orlistat group, respectively. Observation indicators: (1) expression of FASN protein in human GBC cells; (2) effects of orlistat on the proliferation of human GBC NOZ cells; (3) effects of orlistat on apoptosis of human GBC NOZ cells. Measurement data with normal distribution were represented as Mean± SD, the ANOVA test was used for comparison between groups and the least significant difference method was used for pairwise comparison. Results:(1) Expression of FASN protein in human GBC cells. Results of western blot showed that the relative expression of FASN protein in human GBC NOZ, GBC-SD and SGC-996 cells was 0.57±0.06, 0.12±0.04 and 0.10±0.02, respectively, showing a significant difference among them ( F=115.67, P<0.05). There were significant differences between the NOZ cells and the GBC-SD or the SGC-996 cells ( P<0.05), and there was no significant difference between the GBC-SD cells and the SGC-996 cells ( P>0.05). (2) Effects of orlistat on the proliferation of human GBC NOZ cells. ① Results of cell proliferation assay showed that the absorbance value of NOZ cells was 2.34±0.12, 1.57±0.08 and 1.07±0.13 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=205.88, P<0.05). ② Results of clone formation assay showed that the number of NOZ cells clones was 257±23, 153±11 and 83±11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=92.64, P<0.05). ③Results of western blot showed that the relative expression of Cyclin-D1 protein of NOZ cells was 2.31±0.10, 1.52±0.05 and 1.23±0.11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=120.73, P<0.05). The relative expression of CDK-4 protein of NOZ cells was 1.58±0.04, 1.21±0.02 and 1.19±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=110.45, P<0.05). (3) Effects of orlistat on apoptosis of human GBC NOZ cells. Results of western blot showed that the relative expression of Bcl-2 protein of NOZ cells was 1.07±0.03, 0.36±0.03 and 0.15±0.02 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=1 242.93, P<0.05). The relative expression of Bax protein of NOZ cells was 0.51±0.03, 0.38±0.05 and 1.38±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=583.51, P<0.05). Conclusion:Orlistat can inhibit the growth of human GBC NOZ cells and promote their apoptosis.

Research advances in targeted therapy for gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma （GBC） is a type of malignant tumor with an extremely poor prognosis， and at present， surgical operation is the most effective treatment method for this disease. Unfortunately， due to a lack of typical symptoms in the early stage， most patients have progressed to the advanced stage at the time of confirmed diagnosis and lost the opportunity for radical surgery. Among the currently available adjuvant treatments， targeted therapy has higher specificity and fewer side effects and has improved the prognosis of a variety of malignancies. With reference to the latest research advances in targeted therapy for GBC， this article reviews the current research status， potential targets， and targeted medications of targeted therapy for GBC， in order to provide a reference for the clinical treatment of GBC patients.

Advances in the diagnosis and treatment of gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma is a common malignant tumor of the biliary system characterized by poor specificity of early symptoms， a high degree of malignancy， and rapid progression， and it is difficult to make an early diagnosis. Gallstones and gallbladder polyps are considered the most common risk factors for gallbladder carcinoma. Ultrasound is the preferred examination， while CT， MRI， and PET also have their own advantages. There is a lack of radical treatment methods for gallbladder carcinoma， and surgical operation remains the preferred treatment method for gallbladder carcinoma； however， due to the rapid progression of this disease， most patients have lost the opportunity for surgery at the time of diagnosis. A combination of various treatment modalities， such as radiochemotherapy， targeted therapy， and immunotherapy， has improved the prognosis of patients to a certain extent， but with an unsatisfactory long-term therapeutic effect. Therefore， it is of particular importance to give priority to prevention rather than treatment and emphasize early identification and treatment.

Tomografía computada y resonancia magnética en la patología de la vesícula biliar: más allá de la litiasis / Computed tomography and magnetic resonance in gallbladder patology: beyond lithiasis

Resumen La enfermedad de la vesícula biliar es una causa común de dolor abdominal. Si bien por lo general el dolor es secundario a la presencia de litiasis y colecistitis aguda, el espectro de la enfermedad es amplio e incluye anomalías congénitas, otros procesos inflamatorios y neoplasias. La tomografía computada (TC) y la resonancia magnética (RM) tienen un papel relevante en aquellos casos en los que la ecografía no es concluyente y en la planificación del tratamiento. Dentro de las anomalías congénitas, la forma en “gorro frigio” es la más frecuente. Los pólipos son en su mayoría lesiones benignas, siendo las características de malignidad un tamaño superior a 10 mm, solitario y sésil. La adenomiomatosis es reconocible por el engrosamiento de la pared vesicular y los componentes quísticos intramurales. Es importante reconocer el gas intramural e intraluminal en la colecistitis enfisematosa y los microabscesos y hemorragias intraluminales en la colecistitis gangrenosa debido a su alta morbilidad y mortalidad. La colecistitis xantogranulomatosa presenta nódulos intramurales que ocupan más del 60% del área de la pared engrosada y la conservación lineal del realce de la mucosa sin interrupción. El carcinoma vesicular se presenta como una lesión infiltrante que se extiende al hígado, un engrosamiento mural o una masa polipoide intraluminal.

Abstract Gallbladder disease is a common cause of abdominal pain. Although the pain is usually secondary to the presence of lithiasis and acute cholecystitis, the spectrum of the disease is broad and includes congenital anomalies, other inflammatory processes and neoplasms. Computed tomography (CT) and magnetic resonance (MRI) have a relevant role in those cases in which ultrasound is not conclusive and in treatment planning. Among the congenital anomalies, the “phrygian cap” shape is the most frequent. Polyps are mostly benign lesions, with the characteristics of malignancy being larger than 10 mm, solitary and sessile. Adenomyomatosis is recognizable by gallbladder wall thickening and intramural cystic components. It is important to recognize intramural and intraluminal gas in emphysematous cholecystitis and intraluminal microabscesses and hemorrhages in gangrenous cholecystitis because of its high morbidity and mortality. Xanthogranulomatous cholecystitis presents with intramural nodules occupying more than 60% of the thickened wall area and linear preservation of mucosal enhancement without interruption. Gallbladder carcinoma presents as an infiltrative lesion extending to the liver, a mural thickening or an intraluminal polypoid mass.

Cáncer de vesícula en colecistectomías de la región de Tarapacá. Análisis según pertenencia étnica / Prevalence of gallbladder cancer in a Northern Chilean region

BACKGROUND: Gallbladder Cancer (GBC) prevalence varies among countries, associated with different geographical and genetic factors. The Mapuche ethnicity (Ethnia mostly located between the VIII and X Chilean regions) stands out in Chile due to its high GBC prevalence. Aim: To estimate the GBC prevalence in patients undergoing cholecystectomy at a public hospital in the Northern region of Chile (Tarapaca), where other ethnical groups are common. MATERIAL AND METHODS: Pathological reports of 3270 patients (72% women) who underwent cholecystectomy between January 2016 and December 2019 were revised. Subsequently, the accreditation of ethnic belonging for each patient to one of the ten native communities in Chile was requested to the National Corporation for Native Communities Development (CONADI). RESULTS: According to the analysis of pathological reports, the global GBC prevalence was 0.3 %. The prevalence in Aymaras was 0.4% and 0% in Mapuches. The distribution of ethnic origins among analyzed patients was Aymara in 14.3, Mapuche in 2.7%, Diaguita in 1.7%, Quechua in 1.3%, Atacameña in 0.2%, and Colla in 0.2%. No specific ethnic origin was found in 79% of patients. Conclusions: There was a low GBC prevalence rate in Northern Chile and among the Aymara population.

Is the tumor-stroma ratio a prognostic factor in gallbladder cancer?

SUMMARY OBJECTIVE: This study aimed to examine the prognostic effect of the tumor-stroma ratio, which has been shown to have prognostic value in various cancers, in patients with gallbladder cancer who have undergone curative resection. METHODS: The records of gallbladder cancer patients who underwent surgical treatment in our clinic between December 2005 and March 2021 were analyzed retrospectively. The hematoxylin and eosin-stained sections representing the tumors were evaluated under light microscopy to determine tumor-stroma ratio, and based on the results, <50% was defined as the stroma-rich and ≥50% as the stroma-poor groups. RESULTS: A total of 28 patients, including 20 females and 8 males, with a mean age of 64.6 years, were included in this study. Stroma-poor and stroma-rich tumors were detected in 15 and 13 patients, respectively. There was no statistically significant relationship identified between tumor-stroma ratio and advanced age, gender, serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen, incidental or nonincidental diagnosis, jaundice, adjacent organ or structure resection, tumor location, grades 1-2 or 3, T1/T2 or T3/T4, N0 or N1/N2, M stage, American Joint Committee on Cancer stage, lymphovascular invasion, and perineural invasion. The stroma-poor and stroma-rich groups had a 5-year survival rate of 30% and 19.2% and a median overall survival of 25.7 and 15.1 months, respectively, with no statistically significant difference between the groups (p=0.526). CONCLUSIONS: A low tumor-stroma ratio tended to be a poor prognostic factor in gallbladder cancer, although not to a statistically significant degree. This can be considered one of the preliminary studies, as further studies involving larger groups are needed.

Perfil clínico-patológico de pacientes con cáncer hepatobiliar en dos hospitales de referencia en Lima, Perú / Clinicopathological profile of patients with hepatobiliary cancers at two main referral hospitals in Lima, Peru

RESUMEN Objetivo: El objetivo del estudio fue describir las características clínico-patológicas de individuos diagnosticados de cáncer de hígado, vías biliares o vesícula. Materiales y métodos: Entre el 2006 y 2017, se diagnosticaron 89 pacientes (57% mujeres; media: 62 años) con estos canceres en dos hospitales nacionales de Lima, Perú. Resultados: Los resultados mostraron que, independientemente del tipo de cáncer, 64% de los participantes habían sido diagnosticados en estadios avanzados. La anemia fue más frecuente en los pacientes con cáncer de vías biliares e hígado y en estadios avanzados. Se observó mayor frecuencia (32%) de hipertensión arterial (HTA) en el grupo con cáncer de hígado. El análisis por edad mostró que en los pacientes mayores de 50 años la HTA fue más frecuente. Asimismo, sujetos menores de 50 años reportaron antecedentes de infecciones previas en mayor frecuencia (50%), siendo Hepatitis B (HBV) la más común. Conclusiones: Este estudio describe las características clínico-patológicas de base de una neoplasia poco estudiada en el ámbito nacional.

ABSTRACT Objective: The aim of the study was to describe the clinicopathological profile of patients diagnosed with liver, bile ducts or gallbladder cancer. Materials and methods: Between 2006 and 2017, 89 patients (57% female; mean age: 62 years-old) with these cancers were diagnosed at two national hospitals in Lima, Peru. Results: Most patients (64%) had advanced stages of disease. Anemia was more frequent in patients with bile duct and liver cancer and in advanced stages. Hypertension (HTN) was frequent among liver cancer patients (32%). The analysis by age showed that HTN was more frequent in patients over 50 years. Likewise, people under 50 years had more frequent history of previous infections (50%), Hepatitis B (HBV) being the most common. Conclusions: This study describes the baseline clinicopathological characteristics of a malignancy poorly studied in Peru.

Incidental gallbladder cancer: what is the prevalence and how do we perform cholecystectomy for presumably benign biliary disease? / Câncer incidental de vesícula biliar: qual a prevalência e como operamos a colecistectomia por doença presumidamente benigna?

ABSTRACT Objective: to determine the prevalence of incidental gallbladder cancer (IGBC) in cholecystectomies performed in a tertiary public hospital and to describe technical and epidemiological aspects of performing cholecystectomies for presumably benign disease. Method: descriptive, retrospective observational study, based on analysis of medical records of patients undergoing cholecystectomy with preoperative hypothesis of benign disease between January 2018 and January 2022. Results: prevalence of gallbladder adenocarcinoma in our sample was 0.16%, similar to data in the literature. Technical aspects during cholecystectomy were also described with a frequency similar to that found in the literature. Conclusion: despite a rare disease, IGBC is relevant in the routine of the General Surgeon. Its diagnosis, staging and treatment directly affect the prognosis. Technical aspects during cholecystectomy are not always remembered by surgeons and can interfere with the prognosis and subsequent treatment of the patient.

RESUMO Objetivos: determinar a prevalência de câncer incidental de vesícula biliar (CIVB) em colecistectomias realizadas em um hospital público terciário e descrever aspectos técnicos e epidemiológicos na realização de colecistectomias por doença presumidamente benigna. Método: estudo observacional descritivo, retrospectivo, a partir da análise de prontuários de pacientes submetidos à colecistectomia com hipótese pré-operatória de doença benigna entre janeiro de 2018 e janeiro de 2022. Resultados: a prevalência de adenocarcinoma de vesícula biliar na amostra avaliada foi de 0,16%, semelhante aos dados da literatura mundial. Os aspectos técnicos durante a realização da colecistectomia também foram descritos com frequência semelhante ao encontrado na literatura. Conclusão: o CIVB é uma doença rara mas de importância relevante na rotina do Cirurgião Geral. Seu diagnóstico, estadiamento e tratamento implicam diretamente no prognóstico. Aspectos técnicos durante a realização da colecistectomia nem sempre são lembrados pelos cirurgiões e podem interferir no prognóstico e tratamento subsequente do paciente.

Predictive value of clinical radiomics model based on nnU-Net for prognosis of gallbladder carcinoma / 中华消化外科杂志

Objective:To investigate the predictive value of clinical radiomics model based on nnU-Net for the prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 168 patients who underwent curative-intent radical resection of GBC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 61 males and 107 females, aged (64±11)years. All the 168 patients who underwent preoperative enhanced computed tomography (CT) examina-tion were randomly divided into 126 cases in training set and 42 cases in test set according to the ratio of 3:1 based on random number table. For the portal venous phase images, 2 radiologists manually delineated the region of interest (ROI), and constructed a nnU-net model to automatically segment the images. The 5-fold cross-validation and Dice similarity coefficient were used to evaluate the generalization ability and predictive performance of the nnU-net model. The Python software (version 3.7.10) and Pyradiomics toolkit (version 3.0.1) were used to extract the radiomics features, the R software (version 4.1.1) was used to screen the radiomics features, and the variance method, Pearson correlation analysis, one-way COX analysis and random survival forest model were used to screen important radiomics features and calculate the Radiomics score (Radscore). X-tile software (version 3.6.1) was used to determine the best cut-off value of Radscore, and COX proportional hazard regression model was used to analyze the independent factors affecting the prognosis of patients. The training set data were imported into R software (version 4.1.1) to construct a clinical radiomics nomogram model of survival prediction for GBC. Based on the Radscore and the independent clinical factors affecting the prognosis of patients, the Radscore risk model and the clinical model for predicting the survival of GBC were constructed respectively. The C-index, calibration plot and decision curve analysis were used to evaluate the predictive ability of different survival prediction models for GBC. Observation indicators: (1) segmentation results of portal venous phase images in CT examination of GBC; (2) radiomic feature screening and Radscore calculation; (3) prognostic factors analysis of patients after curative-intent radical resection of GBC; (4) construction and evaluation of different survival prediction models for GBC. Measurement data with normal distribution were represented by Mean± SD. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed using the COX proportional hazard regression model. The postoperative overall survival rate was calculated by the life table method. Results:(1) Segmentation results of portal venous phase images in CT examination of GBC: the Dice similarity coefficient of the ROI based on the manual segmentation and nnU-Net segmentation models was 0.92±0.08 in the training set and 0.74±0.15 in the test set, respectively. (2) Radiomic feature screening and Radscore calculation: 1 502 radiomics features were finally extracted from 168 patients. A total of 13 radiomic features (3 shape features and 10 high-order features) were screened by the variance method, Pearson correlation analysis, one-way COX analysis and random survival forest model. Results of random survival forest model analysis and X-tile software analysis showed that the best cut-off values of the Radscore were 6.68 and 25.01. A total of 126 patients in the training set were divided into 41 cases of low-risk (≤6.68), 72 cases of intermediate-risk (>6.68 and <25.01), and 13 cases of high-risk (≥25.01). (3) Prognostic factors analysis of patients after curative-intent radical resection of GBC: the 1-, 2-, and 3-year overall survival rates of 168 patients were 75.8%, 54.9% and 45.7%, respectively. The results of univariate analysis showed that preopera-tive jaundice, serum CA19-9 level, Radscore risk (medium risk and high risk), extent of surgical resection, pathological T staging, pathological N staging, tumor differentiation degree (moderate differentiation and low differentiation) were related factors affecting prognosis of patients in the training set ( hazard ratio=3.28, 3.00, 3.78, 6.34, 4.48, 6.43, 3.35, 7.44, 15.11, 95% confidence interval as 1.91?5.63, 1.76?5.13, 1.76?8.09, 2.49?16.17, 2.30?8.70, 1.57?26.36, 1.96?5.73, 1.02?54.55, 2.04?112.05, P<0.05). Results of multivariate analysis showed that preoperative jaundice, serum CA19-9 level, Radscore risk as high risk and pathological N staging were independent influencing factors for prognosis of patients in the training set ( hazard ratio=2.22, 2.02, 2.89, 2.07, 95% confidence interval as 1.20?4.11, 1.11?3.68, 1.04?8.01, 1.15?3.73, P<0.05). (4) Construction and evaluation of different survival prediction models for GBC. Clinical radiomics model, Radscore risk model and clinical model were established based on the independent influencing factors for prognosis, the C-index of which was 0.775, 0.651 and 0.747 in the training set, and 0.759, 0.633, 0.739 in the test set, respectively. The calibration plots showed that the Radscore risk model, clinical model and clinical radiomics model had good predictive ability for prognosis of patients. The decision curve analysis showed that the prognostic predictive ability of the clinical radiomics model was better than that of the Radscore risk and clinical models. Conclusion:The clinical radiomics model based on the nnU-Net has a good predictive performance for prognosis of GBC.

Laparoscopic radical resection for gallbladder cancer / 中华普通外科杂志

Objective:To investigate the feasibility and clinical efficacy of laparoscopic radical cholecystectomy(LRC) for gallbladder cancer.Methods:The clinical data of 247 patients with gallbladder cancer who underwent radical resection from Jan 2013 to Dec 2019 at Department of General Surgery, Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine was analyzed retrospectively. After propensity score matching, 54 patients were included in laparoscopic group and 103 in laparotomy group. The clinicopathological characteristics and the short- and long-term outcomes were compared.Results:Compared to the laparotomy group, patients in the laparoscopic group had less intraoperative blood loss [100(50,200)ml vs. 200(100,300) ml, Z=4.105, P<0.001], earlier postoperative oral diet[1.0(1.0,2.0) d vs. 2.0(1.0,4.0) d, Z=4.157, P<0.001]and drainage removal[6.5(4.0,12.5) d vs. 9.0(6.0,16.0) d, Z=2.769, P=0.006], shorter hospital stay[7.0(5.0,9.3) d vs. 9.0(8.0,14.0) d, Z=3.923, P<0.001]. The number of lymph node dissection in laparoscopic group was significantly lesser than that in open group [6(4,9) vs. 8(5,12), Z=2.639, P=0.008]. There were no significant differences between the two groups in postoperative complications, short-term and long-term survival outcomes. Conclusions:Laparoscopic radical surgery for gallbladder cancer is as safe and feasible, and identical survival prognosis as open surgery, and moreover a less traumatic procedure.

Prognostic value of using the preoperative serum fibrinogen to albumin ratio in gallbladder carcinoma patients after radical resection / 中华肝胆外科杂志

Objective:To investigate the prognostic value of using preoperative serum albumin-related biomarkers in gallbladder carcinoma (GBC) patients after resection.Methods:The clinical data of patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi’an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Of 427 patients who were included in this study, there were 131 males and 296 females, aged (61.75±10.69) years old, range 30 to 87 years old. The 427 patients were divided into the training set ( n=300) and the testing set ( n=127). The training set was used to develop the nomogram model, and the testing set was used to evaluate its predictive ability. The X-Tile software was used to determine the best cut-off values for prognostic nutritional index (PNI), platelet to albumin ratio (PAR), fibrinogen to albumin ratio (FAR), and albumin to γ-glutamyl transpeptidase ratio (AGR). Based on the independent risk factors screened by the Cox proportional hazards regression model, the nomogram survival prediction model was developed by the rms installation package of the R software. The predictive ability of the nomogram was assessed by C-index and calibration curve. Results:The best cut-off values of PNI, PAR, FAR, and AGR were determined to be 44.0, 6.25×10 9/g, 0.08, and 2.03 g/U, respectively. FAR was better than PNI, PAR and AGR in predicting prognosis of patients after radical resection of GBC. Multivariate analysis showed that FAR>0.08 ( HR=2.124, 95% CI: 1.424-3.168), CEA>5.0 ng/ml ( HR=1.577, 95% CI: 1.047-2.375), CA-125>35.0 U/ml ( HR=1.454, 95% CI: 1.031-2.179), N1-2 stage ( HR=2.074, 95% CI: 1.420-3.029), major vascular invasion ( HR=3.292, 95% CI: 1.640-6.608), perineural infiltration ( HR=1.781, 95% CI: 1.045-3.034) and poor tumor differentiation ( HR=6.100, 95% CI: 2.753-13.515) were independent risk factors affecting prognosis of GBC after radical resection ( P<0.05). The C-index of the nomogram model was 0.790 (95% CI: 0.779-0.801) and 0.771 (95% CI: 0.754-0.788) in the training set and the testing set, respectively. Conclusion:Preoperative FAR had a good predictive ability for overall survival in patients with gallbladder carcinoma after radical resection, and it could be used for prognostic evaluation.