Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

Optimal Lymph Node Staging System in Evaluating Prognosis of Gallbladder Carcinoma: A Multi-institutional Study.

BACKGROUND: Lymph node (LN) involvement is a critical prognostic factor in patients with gallbladder carcinoma (GBC). Controversy exists regarding optimal categorization of nodal metastasis status, including anatomical location of positive nodes (AJCC 7th N staging), number of metastatic lymph nodes (NMLN), log odds of metastatic LNs (LODDS), and lymph node ratio (LNR). METHODS: Patients who underwent curative-intent resection for GBC from six Chinese tertiary hospitals between 2008 and 2013 were analyzed retrospectively. The relative discriminative abilities of the different LN staging systems were assessed by different models including the tree-augmented naïve Bayesian (TAN) model, Cox proportional hazards regression model, and binary logistic regression model. RESULTS: A total of 226 patients were involved in this cohort. Based on the TAN model and composite importance measures, the most important factor affecting the prognosis in the different LN staging systems was NMLN. Among the four TAN models which were built with 4 metastatic LN markers and baseline variables, the accuracy of the NMLN-based prognostic model was 88.15%, higher than 7th N staging (86.44%), LNR (87.34%), and LODDS (85.19%). The Cox model based on NMLN (C-index: 0.763, AIC: 1371.62) had a higher fitness than the others (7th N staging C-index: 0.756, AIC: 1375.51; LNR C-index: 0.759, AIC: 1378.82; LODDS C-index 0.748, AIC: 1390.99). The AUCs of different staging binary logistic regression models were NMLN (0.872), LNR (0.872), 7th N staging (0.869) and LODDS (0.856), respectively. CONCLUSIONS: NMLN was the optimal LN staging system in evaluating prognosis of GBC.

Advances in diagnosis and treatment of hilar cholangiocarcinoma -- a review.

Hilar cholangiocarcinoma (HC) is a rare tumor that causes devastating disease. In the late stages, this carcinoma primarily invades the portal vein and metastasizes to the hepatic lobes; it is associated with a poor prognosis. HC is diagnosed by its clinical manifestation and results of imaging techniques such as ultrasound, computed tomography, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography. Preoperative hepatic bile drainage can improve symptoms associated with insufficient liver and kidney function, coagulopathy, and jaundice. Surgical margin-negative (R0) resection, including major liver resection, is the most effective and potentially curative treatment for HC. If the tumor is not resected, then liver transplantation with adjuvant management can improve survival. We conducted a systematic review of developments in imaging studies and major surgical hepatectomy for HC with positive outcomes regarding quality of life.

Analysis of influencing factors for early tumor recurrence and efficacy of adjuvant chemotherapy in gallbladder carcinoma patients after curative-intent resection: a nationwide, multicenter clinical study / 中华消化外科杂志

Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.

Research progress of perineural invasion in gallbladder cancer / 中华消化外科杂志

As a special mode of tumor metastasis, perineural invasion has been paid more and more attention. It is closely related to prognosis, recurrence and metastasis of tumor after surgery. As the most common malignancy of the biliary tract, perineural invasion is also an inde-pendent prognostic risk factor for gallbladder cancer due to its anatomical location, lymphatic reflux, blood perfusion and innervation. However, there are few studies on perineural invasion in gallbla-dder cancer, especially on its mechanism. By analyzing the general situation and recent progress of perineural invasion in gallbladder cancer, the authors mainly introduce the perineural invasion mechanism, perineural invasion rate of gallbladder cancer, relationship between perineural invasion and the clinical pathologic characteristic, the correlation with the prognosis, relationship with surgi-cal procedures and postoperative adjuvant therapy.

Textbook outcome in gallbladder carcinoma after curative-intent resection: a 10-year retrospective single-center study / 中华医学杂志(英文版)

BACKGROUND@#Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients.@*METHODS@#A total of 540 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. Multivariable logistic regression was used to investigate the factors associated with TO.@*RESULTS@#Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05).@*CONCLUSION@#Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

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.

Impact of number and location of metastatic lymph nodes on prognosis in patients after resection for intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the impact of number and location of metastatic lymph nodes on prognosis of patients after radical resection for intrahepatic cholangiocarcinoma (ICC).Methods:A retrospective study was conducted on 105 patients who underwent radical resection and lymphadenectomy for ICC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2010 to December 2020. There were 49 males and 56 females, with age of (58±10) years old. These patients were divided into 2 groups using the TNM staging (8th edition) into the N0 stage group ( n=62) and N1 stage group ( n=43). Using the NMLN staging, those with 0, 1-2, and >3 number of metastatic lymph nodes (NMLN) were divided into 3 groups: the stage 0 group ( n=62), stage 1 group ( n=24), and stage 2 group ( n=19). Of the 43 patients with lymph node metastasis, they were divided into 2 groups according to whether the lymph node metastasis was limited to the first lymph node station: the first station metastasis group ( n=11) and the non-first station metastasis group ( n=32). The general data, extent of lymph node dissection, pathological examinations, and postoperative survival outcomes of these patients were collected. Determination of risk factors for prognosis of ICC after radical resection was carried out. Results:The median number of lymph node harvested, or the detection of N0 and N1 staging were 6 (3, 8) and 6 (3, 10), respectively. There were no significant differences between the two groups ( Z=-1.10, P>0.05). Overall survival of patients in the N0 stage group was better than the N1 stage group (32.0 vs. 9.0 months, χ 2=23.99, P<0.001). The median survival times of patients in the stage 0, stage 1 and stage 2 groups were 32.0, 14.0 and 6.0 months, respectively. There was a significant difference in overall survival among the 3 groups (χ 2=32.18, P<0.001). The time-dependent receiver operating characteristic curves showed that NMLN staging had better prognostic predictive ability than the N staging. The median survival times of the first station metastasis group and the non-first station metastasis group were 18.0 and 7.0 months, respectively. There was no significant difference between the two groups (χ 2=2.21, P>0.05). Multivariate analysis showed that tumor carbohydrate antigen 125>35.0 U/ml ( HR=4.297, 95% CI:2.418-7.634), hepatolithiasis ( HR=2.713, 95% CI:1.499-4.911), T4 staging ( HR=2.934, 95% CI:1.478-5.825), NMLN stage 1 ( HR=2.759, 95% CI:1.500-5.077) and NMLN stage 2 ( HR=7.376, 95% CI:3.553-15.312) were independent risk factors affecting prognosis of ICC after radical resection ( P<0.05). Conclusion:Lymph node metastasis was an important poor prognostic risk factor after radical resection of intrahepatic cholangiocarcinoma. The prognosis of ICC patients was related to the NMLN, but it was not related to the location of metastatic lymph nodes.

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.

Establishment and application value of a radiomics prediction model for lymph node metas-tasis of gallbladder carcinoma based on dual-phase enhanced CT / 中华消化外科杂志

Objective:To investigate the establishment and application value of a radio-mics prediction model for lymph node metastasis of gallbladder carcinoma based on dual-phase enhanced computed tomography (CT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 194 patients with gallbladder carcinoma who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 70 males and 124 females, aged (64±10)years. All patients underwent curative-intent resection of gallbladder carcinoma. A total of 194 patients were randomly divided into 156 cases in training set and 38 cases in test set according to the ratio of 8:2 based on random number method in R software. The training set was used to establish a diagnostic model, and the test set was used to validate the diagnostic model. After the patients undergoing CT examination, image analysis was performed, radiomics features were extracted, and a radiomics model was established. Based on clinicopathological data, a nomogram prediction model was established. Observation indicators: (1) lymph node dissection and histopathological examination results; (2) establishment and characteristic analysis of a radiomics prediction model; (3) analysis of influencing factors for lymph node metastasis of gallbladder carcinoma; (4) establishment of a nomogram prediction model for lymph node metastasis; (5) comparison of the predictive ability between the radiomics prediction model and nomogram prediction model for lymph node metastasis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparison between groups was performed by the chi-square test. Univariate analysis was conducted by the chi-square test, and multivariate analysis was performed by the Logistic regression model forward method. The receiver operating characteristic curve was drawn, and the area under curve, decision curve, confusion matrix were used to evaluate the predictive ability of prediction models. Results:(1) Lymph node dissection and histopathological examination results. Of the 194 patients, 182 cases underwent lymph node dissection, with the number of lymph node dissected as 8(range, 1?34) per person and the number of positive lymph node as 0(range, 0?11) per person. Postoperative histopathological examination results of 194 patients: 122 patients were in stage N0, with the number of lymph node dissected as 7(range, 0?27) per person, 48 patients were in stage N1, with the number of lymph node dissected as 8(range, 2?34) per person and the number of positive lymph node as 1(range, 1?3) per person, 24 patients were in stage N2, with the number of lymph node dissected as 11(range, 2?20) per person and the number of positive lymph node as 5(range, 4?11) per person. (2) Establishment and characteristic analysis of a radiomics prediction model. There were 107 radiomics features extracted from 194 patients, including 18 first-order features, 14 shape features and 75 texture features. According to the intra-group correlation coefficient and absolute median difference of each radiomics feature, mutual information, Select K-Best, least absolute shrinkage and selection operator regression were conducted to further reduce dimensionality. By further combining 5 different machine learning algorithms including random forest, gradient boosting secession tree, support vector machine (SVM), K-Nearest Neighbors and Logistic regression, the result showed that the Select K-Best_SVM model had the best predictive performance after analysis, with the area under receiver operating characteristic curve as 0.76 in the test set. (3) Analysis of influencing factors for lymph node metastasis of gallbladder carcinoma. Results of univariate analysis showed that systemic inflammation response index, carcinoembryonic antigen (CEA), CA19-9, CA125, radiological T staging and radiological lymph node status were related factors for lymph node metastasis of patients with gallbladder cancer ( χ2=4.20, 11.39, 5.68, 11.79, 10.83, 18.58, P<0.05). Results of multivariate analysis showed that carcinoembryonic antigen, CA125, radiological T staging (stage T3 versus stage T1?2, stage T4 versus stage T1?2), radiological lymph node status were independent influencing factors for lymph node metastasis of patients with gallbladder carcinoma [ hazard ratio=2.79, 4.41, 5.62, 5.84, 3.99, 95% confidence interval ( CI) as 1.20?6.47, 1.81?10.74, 1.50?21.01, 1.02?33.31, 1.87?8.55, P<0.05]. (4) Establishment of a nomogram prediction model for lymph node metastasis. A nomogram prediction model was established based on the 4 independent influencing factors for lymph node metastasis of gallbladder carcinoma, including CEA, CA125, radiological T staging and radiological lymph node status. The concordance index of the nomogram model was 0.77 (95% CI as 0.75?0.79) in the training set and 0.73 (95% CI as 0.68?0.72) in the test set, respectively. (5) Comparison of the predictive ability between the radiomics predic-tion model and nomogram prediction model for lymph node metastasis. The receiver operating characteristic curve showed that the areas under the curve of Select K-Best_SVM radiomics model were 0.75 (95% CI as 0.74?0.76) in the training set and 0.76 (95% CI as 0.75?0.78) in the test set, respectively. The areas under the curve of nomogram prediction model were 0.77 (95% CI as 0.76?0.78) in the training set and 0.70 (95% CI as 0.68?0.72) in the test set, respectively. The decision curve analysis showed that Select K-Best_SVM radiomics model and nomogram prediction model had a similar ability to predict lymph node metastasis. The confusion matrix showed that Select K-Best_SVM radiomics model had the sensitivity as 64.29% and 75.00%, the specificity as 73.00% and 59.09% in the training set and test set, respectively. The nomogram had the sensitivity as 51.79% and 50.00%, the specificity as 80.00% and 72.27% in the training set and test set, respectively. Conclusion:A dual-phase enhanced CT imaging radiomics prediction model for lymph node metastasis of gallbladder carcinoma is successfully established, and its predictive ability is good and consistent with that of nomogram.

Hotspots and disputes concerning surgical management of gallbladder cancer / 西安交通大学学报(医学版)

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary tract, with a high degree of malignancy and poor prognosis. R0 resection is the basic principle of surgical treatment of GBC. However, disputes still exist over the extent of liver resection, extrahepatic bile duct resection, range of lymphadenectomy, surgical treatment of GBC diagnosed during or after surgery, and the application of laparoscopy in GBC. This paper reviews the progress in surgical treatment of GBC and discusses the disputes over surgical treatment in order to provide reference for clinical research and treatment of GBC in clinical work.

Progress in diagnosis and treatment of gallbladder carcinoma in the past 60 years / 西安交通大学学报(医学版)

The First Affiliated Hospital of Xi’an Jiaotong University has experienced more than 60 years’ history in the diagnosis and treatment of gallbladder carcinoma (GBC). From 1956 to 2018, 3 430 cases of GBC were treated, including 1941 cases of surgical treatment and 703 cases of radical resection. The data comparison between 1956-2008 and 2009-2018 revealed that the radical resection rate increased from 19.9% to 48.3%. The mean survival time after regional radical resection and extended radical resection was (23.1±15.4) and (17.5±16.2) months, respectively, from 2004 to 2008. Compared with those between 2013 and 2017, the mean survival time after regional radical resection and extended radical resection was (31.5±2.0) and (18.6±3.9) months, respectively, and the median survival time was 31.0 and 11.0 months, respectively. By comparing the GBC data longitudinally, the mode of diagnosis and treatment of GBC in our hospital has changed significantly in the past 10 years, which is mainly reflected in the change of GBC staging system, the progress of imaging diagnosis mode, the standardization of surgery and the development of adjuvant treatment. All of these have significantly improved the prognosis of GBC.

Gallbladder cancer-associated fibroblasts promote the migration of lymphatic endothelial cells via releasing IGFBP3 / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of gallbladder cancer-associated fibroblasts (CAFs) on the migration of lymphatic endothelial cells (LECs) so as to elucidate the molecular mechanisms involved. 【Methods】 The CAFs and normal fibroblasts (NFs) were extracted by enzymatic digestion, and the supernatant (CM) of CAFs and NFs was collected. The levels of IL-6, IGFBP3 and other related cytokines were detected by semi-quantitative protein factor microarray and ELISA. The expressions of α-SMA (CAFs maker) and IGFBP3 in gallbladder cancer and para-cancer tissues were detected by immunohistochemistry, and the correlation of α-SMA and IGFBP3 expressions with clinicopathological characteristics were analyzed. LECs were cultured and divided into serum-free medium group (control group), CAF-CM co-culture group, NF-CM co-culture group, IGFBP3 group, and CAF-CM+IGFBP3 inhibitor (2-Deoxy-D-glucose, 2-DG) group according to different treatment. Transwell migration assays and wound healing assays were applied to analyze the migration ability of LECs under different treatment. The expressions of E-cadherin, N-cadherin and Vimentin were detected by Western blotting. 【Results】 Protein factor microarray and ELISA showed that the concentration of IGFBP3 in CAF-CM was significantly increased, and the expression of α-SMA was significantly related to lymph node metastasis, advanced TNM stage and expression of IGFBP3. IGFBP3 secreted from CAF-CM significantly promoted LECs migration, up-regulated the expression of N-cadherin and Vimentin, and down-regulated the expression of E-cadherin. Treatment with IGFBP3 inhibitor 2-DG could reverse the effect of CAF-CM on migration of LECs and related protein expressions. 【Conclusion】 Gallbladder CAFs promote the migration of LECs via releasing IGFBP3, which affects EMT transformation.

Expressions of TP53, P16 and K-ras in gallbladder high-grade intraepithelial neoplasia and early carcinoma and establishment of a random forest prediction model / 西安交通大学学报(医学版)

【Objective】 To explore the different expressions of TP53, P16 and K-ras in gallbladder high-grade intraepithelial neoplasia and early carcinoma, and establish their mutation random forest prediction model. 【Methods】 We retrospectively analyzed the clinicopathological data of 71 patients who underwent cholecystectomy at The First Affiliated Hospital of Xi’an Jiaotong University from January 2013 to December 2018, including 20 cases of chronic cholecystitis, 28 cases of gallbladder high-grade intraepithelial neoplasia, and 23 cases of early gallbladder carcinoma. The immunohistochemical SP method was conducted to detect the expressions of TP53, P16 and K-ras in the gallbladder pathological tissues; the correlation between the above genes and clinicopathological data was analyzed. A random forest prediction model of each gene mutation was established based on the clinicopathological data and gene expression. 【Results】 The positive expressions of TP53, P16 and K-ras were related to the gallbladder with cholecystolithiasis or polyps and gallbladder pathological tissue type. The positive rates of the three genes in the gallbladder polyps were significantly higher than those in the cholecystolithiasis group (P<0.05). The positive rates of the three genes in the latter two groups of gallbladder high-grade intraepithelial neoplasia and early gallbladder carcinoma were significantly higher than those in the chronic cholecystitis (P<0.05), while there was no statistical difference between the latter two groups (P>0.05). The mutations of TP53, P16 and K-ras had a certain correlation (χ2=6.285, 19.595, 4.070, r=0.298, 0.525, 0.239, P<0.05). TP53, P16 and K-ras mutation prediction models based on random forest had good accuracy (AUC=77.42%, 80.06%, 71.75%, accuracy=76.06%, 76.06%, 67.61%). 【Conclusion】 TP53, P16 and K-ras gene mutations promote the transformation of chronic cholecystitis to gallbladder carcinoma. The mutation prediction model based on random forest has a good accuracy, which can provide an important reference for carcinogenesis and early diagnosis of gallbladder carcinoma.

Advances in surgical management of primary carcinoma of the gallbladder: Results from 10-year research at a single institution / 西安交通大学学报(医学版)

【Objective】 To analyze the clinical characteristics of patients with primary carcinoma of the gallbladder (PGC) who underwent radical intent resection in our center in the last decade and the therapeutic effects of the operation. 【Methods】 A single-institution database of The First Affiliated Hospital of Xi'an Jiaotong University from January 2008 to December 2017 was queried for patients with PGC who had received surgical treatment. The data were studied retrospectively to assess the trend of total admission, radical resection rate, prognosis and clinicopathological characteristics of PGC in the last decade. 【Results】 A total of 2 159 patients with PGC were treated in our institution from 2008 to 2017. Of them, 1072 were surgically treated and 503 underwent radical intent resection. In the past 5 years (2013-2017), the radical resection rate was 26.5% (319 cases of the operation), which was significantly higher than that in 2008-2012 (19.2%) (P<0.001). The overall survival time of the patients who underwent radical resection was 32 months, and the 1-, 3-, and 5-year survival rate was 68.9%, 48.4% and 41.6%, respectively. Compared with the data of 2008-2012, the proportion of the patients with preoperative jaundice decreased in the past 5 years (7.8% vs. 14.7%, P<0.05), that of the patients who underwent D2 lymphadenectomy (74.0% vs. 26.1%, P<0.001) increased significantly (P<0.001), the total number of lymph nodes obtained from the dissection (8.07±5.18 vs. 5.89±3.14, P<0.001) increased significantly (95.6% vs. 89.7%, P<0.05), and the proportion of R0 resection (95.6%) increased significantly (P<0.05). 【Conclusion】 The diagnosis and treatment of radical intent resection of PGC in our hospital have changed significantly in the last decade, mainly reflected in the extension of lymphadenectomy, increase in R0 resection rate and decrease in patients with preoperative jaundice.

Analysis of prognostic factors of patients with intrahepatic cholangiocarcinoma and establishment of a nomogram for survival prediction / 国际外科学杂志

Objective@#To explore the prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) after surgical resection and establish a nomogram for survival prediction.@*Methods@#A total of 160 patients with ICC who underwent surgical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Among them, 89 patients were males and 71 were females, aged from 29 to 81 years with a age of (57.41±10.35) years. Observation indicators included: (1) The result of follow-up: postoperative survival. (2) The univariate analysis and multivariate analysis affecting postoperative patients′ prognosis. (3) The establishment and validation of nomogram model. The follow-up using outpatient and telephone was performed once every 3 months within 1 year postoperatively and once every 3-6 months after 1 year postoperatively up to August 1, 2019. The follow-up included liver function, CA19-9, upper abdominal ultrasound, CT or MRI. The overall postoperative survival time, end point of observation, was the date from the operation date to the follow-up date, or the date of death due to tumor recurrence and metastasis. The patients′ clinicopathological data was included in the prognostic factor analysis, the Kaplan-meier method and Log-rank test were conducted for the univariate analysis, the Cox proportional risk regression model was used for the multivariate analysis. The independent risk factors based on Cox regression model were screened to establish a nomogram for postoperative survival prediction. The patients were divided into the model group (n=112) for the establishment of survival nomogram and the validation group (n=48) for the assessment of predictive ability at a ratio of 7∶3, and the accuracy of nomogram in postoperative survival prediction was assessed by c-index. Measurement data with normal distribution were expressed with (Mean±SD). Measurement data with skewed distribution were described as M (range). Count data were expressed as cases and percentage.@*Results@#During the follow-up period, all patients with ICC after surgical resection were followed up for a survival time of 20 months (2-111 months). 100 patients died of multiple organ failure caused by tumor recurrence and metastasis and 60 patients survived. The 1-, 3- and 5-year overall survival rates of patients were 63.3%, 30.0% and 19.6%, respectively. Univariate analysis showed that CA19-9, hepatolithiasis, number of tumor, range of liver resection, tumor differentiation, pathology type, tumor diameter, vascular invasion, TNM stage, lymphatic metastasis, satellite foci and surgical margin were the prognostic factors of ICC patients after surgical resection (HR=1.78, 1.97, 2.91, 1.89, 3.06, 2.86, 2.07, 1.94, 2.24, 1.95, 2.68, 2.00, 95%CI: 1.12-2.85, 1.22-3.16, 1.85-4.56, 1.26-2.85, 1.38-6.82, 1.31-6.25, 1.37-3.14, 1.07-3.51, 1.24-4.06, 1.26-3.01, 1.28-5.60, 1.11-3.59, P<0.05). Multivariate analysis showed that hepatolithiasis, number of tumor, range of liver resection, tumor differentiation (low differentiation) and pathology type were independent risk factors of ICC patients after surgical resection (HR=2.47, 2.37, 2.06, 5.52, 5.72, 95%CI: 1.39-4.38, 1.44-3.91, 1.25-3.40, 1.24-24.49, 2.31-14.17, P<0.05). The nomogram was established based on above five independent risk factors, the c-index value for postoperative survival of the model group and validation group were 0.71 (95%CI: 0.64-0.79) and 0.71(95%CI: 0.61-0.81), respectively.@*Conclusion@#A nomogram based on hepatolithiasis, number of tumor, range of liver resection, tumor differentiation and pathology type has better accuracy in postoperative survival prediction for patients with ICC.

Analysis of prognostic factors of patients with intrahepatic cholangiocarcinoma and establishment of a nomogram for survival prediction / 国际外科学杂志

Objective To explore the prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) after surgical resection and establish a nomogram for survival prediction.Methods A total of 160 patients with ICC who underwent surgical resection in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed.Among them,89 patients were males and 71 were females,aged from 29 to 81 years with a age of (57.41 ± 10.35) years.Observation indicators included:(1) The result of follow-up:postoperative survival.(2) The univariate analysis and multivariate analysis affecting postoperative patients' prognosis.(3) The establishment and validation of nomogram model.The follow-up using outpatient and telephone was performed once every 3 months within 1 year postoperatively and once every 3-6 months after 1 year postoperatively up to August 1,2019.The follow-up included liver function,CA19-9,upper abdominal ultrasound,CT or MRI.The overall postoperative survival time,end point of observation,was the date from the operation date to the follow-up date,or the date of death due to tumor recurrence and metastasis.The patients' clinicopathological data was included in the prognostic factor analysis,the Kaplan-meier method and Log-rank test were conducted for the univariate analysis,the Cox proportional risk regression model was used for the multivariate analysis.The independent risk factors based on Cox regression model were screened to establish a nomogram for postoperative survival prediction.The patients were divided into the model group (n =112) for the establishment of survival nomogram and the validation group (n =48) for the assessment of predictive ability at a ratio of 7∶ 3,and the accuracy of nomogram in postoperative survival prediction was assessed by c-index.Measurement data with normal distribution were expressed with (Mean ± SD).Measurement data with skewed distribution were described as M (range).Count data were expressed as cases and percentage.Results During the follow-up period,all patients with ICC after surgical resection were followed up for a survival time of 20 months (2-111 months).100 patients died of multiple organ failure caused by tumor recurrence and metastasis and 60 patients survived.The 1-,3-and 5-year overall survival rates of patients were 63.3％,30.0％ and 19.6％,respectively.Univariate analysis showed that CA19-9,hepatolithiasis,number of tumor,range of liver resection,tumor differentiation,pathology type,tumor diameter,vascular invasion,TNM stage,lymphatic metastasis,satellite foci and surgical margin were the prognostic factors of ICC patients after surgical resection (HR =1.78,1.97,2.91,1.89,3.06,2.86,2.07,1.94,2.24,1.95,2.68,2.00,95 ％ CI:1.12-2.85,1.22-3.16,1.85-4.56,1.26-2.85,1.38-6.82,1.31-6.25,1.37-3.14,1.07-3.51,1.24-4.06,1.26-3.01,1.28-5.60,1.11-3.59,P ＜ 0.05).Multivariate analysis showed that hepatolithiasis,number of tumor,range of liver resection,tumor differentiation (low differentiation) and pathology type were independent risk factors of ICC patients after surgical resection (HR =2.47,2.37,2.06,5.52,5.72,95％ CI:1.39-4.38,1.44-3.91,1.25-3.40,1.24-24.49,2.31-14.17,P ＜ 0.05).The nomogram was established based on above five independent risk factors,the c-index value for postoperative survival of the model group and validation group were 0.71 (95％ CI:0.64-0.79) and 0.71 (95％ CI:0.61-0.81),respectively.Conclusion A nomogram based on hepatolithiasis,number of tumor,range of liver resection,tumor differentiation and pathology type has better accuracy in postoperative survival prediction for patients with ICC.

A multicenter retrospective study on surgical indications of gallbladder polyps: a report of 2 272 cases / 中华消化外科杂志

Objective:To investigate the surgical indications of gallbladder polyps.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 272 patients with gallbladder polyps who underwent cholecystectomy in 11 medical centers from January 2015 to December 2019 were collected, including 585 in the First Affiliated Hospital of Xi′an Jiaotong University, 352 in No. 215 Hospital of Shaanxi Nuclear Industry, 332 in the First People′s Hospital of Xianyang, 233 in Shaanxi Provincial People′s Hospital, 152 in the Second Affiliated Hospital of Xi′an Jiaotong University, 138 in Xianyang Hospital of Yan′an University, 137 in People′s Hospital of Baoji, 125 in Hanzhong Central Hospital, 95 in Baoji Central Hospital, 72 in Ankang Central Hospital, 51 in Yulin No.2 Hospital. There were 887 males and 1 385 females, aged (48±12)years, with a range from 12 to 86 years. Observation indicators: (1) surgical treatment, pathological examination and hospitalization; (2) follow-up and complications; (3) comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps; (4) comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis; (5) analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis; (6) construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Follow-up using outpatient examination or telephone interview was conducted to detect complications and survival of patients up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the rank-sum test. Ordinal data was analyzed using the rank-sum test of multi-samples. Analysis of influence factors for the incidence of neoplastic polyps was conducted after excluding missing data of CEA and CA19-9. Univariate analysis was conducted using the chi-square test or rank-sum test of multi-samples, and multivariate analysis was conducted using Logistic regression model. Based on Logistic regression model multivariate analysis, the nomogram prediction model was constructed using the R 3.6.0 version software. Results:(1) Surgical treatment, pathological examination and hospitalization: of the 2 272 patients, 2 199 cases underwent laparoscopic cholecystectomy, 43 cases underwent open cholecystectomy, 28 cases underwent radical resection for gallbladder carcinoma, and 2 cases underwent laparoscopic gallbladder preservation and polypectomy. There were 1 050 of the 2 272 patients undergoing intraoperative frozen section examination. Results of pathological examination showed that 1 953 of the 2 272 patients had non-neoplastic polyps including 1 681 cases with cholesterol polyps and 272 cases with inflammatory polyps; 319 cases had neoplastic polyps including 274 with benign polyps (93 cases with adenoma, 66 cases with adenomyoma, 81 cases with adenoma-like hyperplasia, 34 cases with adenoma combined with intraepithelial neoplasia); and 45 cases had malignant polyps including 43 cases with adenocarcinoma, 1 case with adenosquamous carcinoma and 1 case with sarcomatoid carcinoma. The duration of postoperative hospital stay of 2 272 patients was 3 days(range, 1 to 27 days). (2) Follow-up and complications: of the 2 272 patients, 1 932 were followed up for 3.5 to 63.5 months, with a median follow-up time of 31.0 months. During the follow-up, 180 patients had short-term complications and 170 patients had long-term complications. (3) Comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps: cases with age ≤50 years or >50 years, cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, CA125, cases with single or multiple polyps in preoperative ultrasonography examination, cases with diameter of polyps in preoperative ultrasonography examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasono-graphy examination as nodular, papillary, globular or mulberry-like, cases undergoing or not undergoing intraoperative frozen section examination, cases with diameter of polyps in postoperative pathological examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with gallbladder wall thickness in postoperative pathological examination as ≤4 mm or >4 mm of the 1 953 patients with non-neoplastic polyps were 1 118, 835, 1 027, 422, 230, 274, 2.0 mg/L(range, 0.2-8.6 mg/L), 14.5 U/mL(range, 2.6-116.4 U/mL), 10.5 U/mL(range, 1.2-58.7 U/mL), 658, 1 295, 674, 741, 413, 125, 1 389, 564, 407, 1 119, 292, 135, 832, 1 121, 698, 774, 385, 96, 1 719, 234, respectively. The above indicators of the 319 patients with neoplastic polyps were 160, 159, 204, 55, 26, 34, 2.9 mg/L(range, 0.2-28.8 mg/L), 19.7 U/mL(range, 3.5-437.1 U/mL), 15.0 U/mL(range, 1.0-945.0 U/mL), 203, 116, 49, 59, 100, 111, 154, 165, 92, 153, 49, 25, 218, 101, 53, 85, 90, 91, 263, 56, respectively. There were significant differences in the above indicators between the non-neoplastic polyps and neoplastic polyps patients ( χ2=5.599, Z=-3.668, -2.407, -3.023, -3.403, χ2=104.474, Z=-13.367, χ2=65.676, 12.622, 73.075, Z=-11.874, χ2=7.649, P<0.05). (4) Comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis: after excluding 311 of the 2 272 patients with cholecystolithiasis, there were 706 cases with gallbladder polyp diameter of 7 to 9 mm, 459 cases with gallbladder polyp diameter of 10 to 12 mm, and 205 cases with gallbladder polyp diameter ≥13 mm, respectively. Cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, cases with single or multiple polyps in preoperative ultrasonography examination, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasonography examination as nodular, papillary, globular or mulberry-like, cases with echo intensity of preoperative ultrasonography examination as slightly strong, medium or weak, cases undergoing or not undergoing intraoperative frozen section examination, and cases with pathological types of polyps as non-neoplastic polyps, benign polyps or malignant polyps of the 706 patients with gallbladder polyp diameter of 7 to 9 mm were 291, 170, 107, 138, 2.2 mg/L(range, 0.5-8.6 mg/L), 21.0 U/mL(range, 2.8-116.4 U/mL), 207, 499, 620, 86, 118, 463, 75, 50, 252, 410, 44, 379, 327, 657, 49, 0, respectively. The above indicators of the 459 patients with gallbladder polyp diameter of 10 to 12 mm were 267, 85, 43, 64, 1.6 mg/L(range, 0.4-9.3 mg/L), 10.4 U/mL(range, 3.3-354.0 U/mL), 205, 254, 237, 222, 158, 223, 51, 27, 222, 213, 24, 263, 196, 373, 79, 7, respectively. The above indicators of the 205 patients with gallbladder polyp diameter ≥13 mm were 128, 38, 20, 19, 2.1 mg/L(range, 0.6-28.8 mg/L), 10.2 U/mL(range, 3.6-307.0 U/mL), 120, 85, 75, 130, 68, 97, 22, 18, 98, 95, 12, 148, 57, 113, 71, 21, respectively. There were significant differences in the above indicators among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥ 13 mm ( χ2=46.482, 8.093, 39.504, 66.971, 277.043, 60.945, 19.672, 22.340, 197.854, P<0.05). (5) Analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: of the 459 patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis, there were 373 cases with non-neoplastic polyps, and 86 cases with neoplastic polyps, respectively. Results of univariate analysis showed that CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( χ2=10.342, 5.616, 20.009, Z=-4.352, χ2=6.203, P<0.05). Results of multivariate analysis showed that CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( odds ratio=8.423, 0.082, 0.337, 3.694, 2.318, 95% confidence interval: 1.547-45.843, 0.015-0.443, 0.198-0.575, 1.987-6.866, 1.372-3.916, P<0.05). (6) Construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were imported into R 3.6.0 version software to establish the nomogram prediction model for neoplastic polyps. The results showed the score for CEA>5.0 mg/L, CA19-9>39.0 U/mL, cases with single polyp in preoperative ultrasonography examination, cases with polyp diameter of 10 mm in preoperative ultrasonography examination, cases with polyp diameter of 11 mm in preoperative ultrasonography examination, cases with polyp diameter of 12 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were 25, 27, 100, 0, 26, 72, 98 in the nomogram prediction model, respectively. The C-index of nomogram prediction model was 0.768. Result of nomogram prediction model showed that the incidence of tumor polyps was 0, 6% and 10% in patients with multiple and pedicled gallbladder polyps with diameter of 10, 11, 12 mm and with CEA ≤5.0 mg/L and CA19-9 ≤39.0 U/mL, the incidence of tumor polyps was 43%, 53% and 70% in patients with single and broad base gallbladder polyps with diameter of 10, 11, 12 mm. The calibration curve showed that the probability of the nomogram prediction model predicting neoplastic polyps was nearly consistent with the actual probability. Conclusions:CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination are independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Cholecystectomy should be performed in time for patients with single and broad based gallbladder polyps with diameter of 10, 11, 12 mm.

Effects of the extent of regional lymph node dissection on the prognosis of patients with T4 gallbladder carcinoma: a multi-center retrospective analysis / 中华消化外科杂志

Objective To investigate the effects of the extent of regional lymph node dissection on the prognosis of patients with T4 gallbladder carcinoma.Methods The retrospective cohort study was conducted.The clinicopathological data of 64 patients with T4 gallbladder carcinoma who underwent radical cholecystectomy in the 4 medical centers between January 2013 and December 2016 were collected,including 31 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,16 in the First Affiliated Hospital of Xi'an Jiaotong University,11 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 6 in the Affiliated Hospital of North Sichuan Medical College.There were 27 males and 37 females,aged from 35 to 77 years,with a median age of 59 years.Sixty-four patients underwent radical cholecystectomy and regional lymph node dissection.According to the extent of intraoperative lymph node dissection,25 patients (13 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,6 in the First Affiliated Hospital of Xi'an Jiaotong University,4 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 2 in the Affiliated Hospital of North Sichuan Medical College) whose extent of lymph node dissection involved lymph nodes next to cystic duct,hepatoduodenal ligament,back of head of pancreas,next to common hepatic artery and celiac trunk were allocated into the extended dissection group,39 patients (18 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,10 in the First Affiliated Hospital of Xi'an Jiaotong University,7 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 4 in the Affiliated Hospital of North Sichuan Medical College) whose extent of lymph node dissection involved lymph nodes next to cystic duct and hepatoduodenal ligament were allocated into the control group.Observation indicators:(1) postoperative complications;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival up to January 2018.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated with the independentsample t test.Count data were represented as absolute number or percentage,and comparison between groups was analyzed using the chi-square test and Fisher exact probability.The survival curve was drawn using the KaplanMeier method,and the comparison of survival rates was done by the Log-rank test.Results (1) Postoperative complications:64 patients with T4 gallbladder carcinoma underwent successful radical cholecystectomy and regional lymph node dissection,without intraoperative death.Twelve patients had different degrees of postoperative complications.Four of 7 patients undergoing extended radical cholecystectomy had postoperative complications.Twenty-five patients in the extended dissection group were cured by conservative treatment,including 4 with intraperitoneal infection and 2 with pancreatic leakage,with a complication incidence of 24.0％ (6/25).Thirtynine patients in the control group were cured by conservative treatment,including 5 with intraperitoneal infection and 1 with gastric retention,with a complication incidence of 15.4％ (6/39).There was no statistically significant difference in the complication incidence between the two groups (x2=0.284,P＞0.05).(2) Follow-up and survival situations:64 patients were followed up for 1-60 months.The postoperative overall median survival time was l l months.The postoperative median survival time,1-,3-and 5-year cumulative survival rates were respectively 18 months,80％,16％,9％ in the extended dissection group and 8 months,21％,4％,0 in the control group,with a statistically significant difference in the prognosis between the two groups (x2=14.744,P＜ 0.05).Conclusions On the premise of practiced surgical skill,extended regional lymph node dissection cannot increase incidence of surgical complication in patients with T4 gallbladder carcinoma after radical resection.Actively extending lymph node dissection up to near common hepatic artery,peri-celiac trunk and back of head of pancreas can improve long-term survival and prognosis.

Clinical effects and prognostic analysis of radical surgery for primary gallbladder cancer / 中华消化外科杂志

Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06％ (174/207),85.71％ (168/196) and 63.11％ (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34％ (145/262),48.06％ (124/258) and 46.15％ (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6％ and 45.8％.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P＜0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95％ confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P＜0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95％ CI:0.15-0.82,P＜0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.