Intrahepatic cholangiocarcinoma(ICC)is a highly aggressive liver malignancy characterized by a subtle onset and rapid progression.Most patients are diagnosed at advanced stages,making radical surgical resection impossible,and the overall prognosis is poor.The ability to convert initially unresectable ICC to resectable tumors through multimodal comprehensive treatment is significant for prolonging patient survival.In recent years,with the application of immunotherapy and targeted therapy in advanced ICC,as well as improvements in surgical techniques,radiation therapy,hepatic arterial infusion chemotherapy,and selective internal radiation therapy,along with updates in treatment strategies and concepts,some initially unresectable ICC tumors have become resectable following downstaging with various treatment modalities,which has brought new hope for improving conversion resection success rates and patient prognosis.However,conversion therapy for ICC still faces numerous challenges and controversies,including the lack of a recognized standard treatment regimen,limited overall conversion success rates,a lack of long-term follow-up data to demonstrate survival benefits after conversion resection,and unresolved issues such as whether patients who achieve clinical complete remission should undergo resection or be monitored.Given that most current studies on ICC conversion therapy are small-sample,retrospective studies or case reports,lacking high-level evidence from randomized controlled trials,and the majority of studies include various types of biliary tract cancers without considering the heterogeneity across different anatomical locations,the relevance of these findings for guiding ICC conversion treatment strategies is limited.There is an urgent need for high-quality,multi-center,large-sample,prospective clinical studies and basic research to explore optimal ICC translational therapy regimens with rapid efficacy,high objective response rates,and good safety profiles,identify patient populations with potential benefits from different treatments,and develop individualized treatment strategies to improve conversion success rates and ultimately enhance patient prognosis.This article reviews the progress in the conversion treatment of unresectable ICC,intending to provide a reference for clinical practice.

Intrahepatic cholangiocarcinoma(ICC)is a highly aggressive liver malignancy characterized by a subtle onset and rapid progression.Most patients are diagnosed at advanced stages,making radical surgical resection impossible,and the overall prognosis is poor.The ability to convert initially unresectable ICC to resectable tumors through multimodal comprehensive treatment is significant for prolonging patient survival.In recent years,with the application of immunotherapy and targeted therapy in advanced ICC,as well as improvements in surgical techniques,radiation therapy,hepatic arterial infusion chemotherapy,and selective internal radiation therapy,along with updates in treatment strategies and concepts,some initially unresectable ICC tumors have become resectable following downstaging with various treatment modalities,which has brought new hope for improving conversion resection success rates and patient prognosis.However,conversion therapy for ICC still faces numerous challenges and controversies,including the lack of a recognized standard treatment regimen,limited overall conversion success rates,a lack of long-term follow-up data to demonstrate survival benefits after conversion resection,and unresolved issues such as whether patients who achieve clinical complete remission should undergo resection or be monitored.Given that most current studies on ICC conversion therapy are small-sample,retrospective studies or case reports,lacking high-level evidence from randomized controlled trials,and the majority of studies include various types of biliary tract cancers without considering the heterogeneity across different anatomical locations,the relevance of these findings for guiding ICC conversion treatment strategies is limited.There is an urgent need for high-quality,multi-center,large-sample,prospective clinical studies and basic research to explore optimal ICC translational therapy regimens with rapid efficacy,high objective response rates,and good safety profiles,identify patient populations with potential benefits from different treatments,and develop individualized treatment strategies to improve conversion success rates and ultimately enhance patient prognosis.This article reviews the progress in the conversion treatment of unresectable ICC,intending to provide a reference for clinical practice.

Intrahepatic cholangiocarcinoma （ICC） ranks second among malignant liver tumors and has high malignancy and poor prognosis. Currently， surgical treatment remains the only potentially curative therapy for ICC， but with a relatively low R0 resection rate and a short recurrence-free survival time after surgery. There are still several issues that need to be clarified， such as reasonable margin width， the value of anatomical hepatectomy， the role of lymph node dissection， and the oncological efficacy of laparoscopic liver resection and liver transplantation. This article reviews the research advances in surgical treatment strategies for ICC and related controversies， in order to provide a reference for clinical decision-making.

Objective:To explore the clinical outcome of early endoscopic realignment with flexible cystoscope for pelvic fracture urethral injury.Methods:We retrospectively collected and analyzed the clinical data of patients with pelvic fracture urethral injuries in ER of Beijing Jishuitan Hospital from March 2018 to June 2022.Seventy-six male patients with PFUI were reviewed and 60 patients were included due to the integrity of data collected. The patients were divided into early endoscopic realignment (EER) group and suprapubic cystostomy (SC) group according to the acute management. There were 33 patients and 27 patients in EER group and SC group, respectively. The age of the patients were (42.2±13.8)years and (44.1±15.0) years in EER group and SC group, respectively. The causes of the injuries were car accident, falling and crush, the percentage of the patients were 60.6%(20 cases), 33.3%(11 cases), 6.1%(2 cases) and 55.6%(15 cases), 44.4%(12 cases), 0 in EER group and SC group, respectively. The difference between two groups was statistically insignificant. The procedure of EER began with a cystostomy guided by B ultrasound, then an antegrade cystoscopy was performed through the cystostomy while negociating the bladder neck to the proximal side of injured urethra. A ureteral stent was inserted into the broken urethra and retrieved by a forceps through retrograde urethroscopy with another flexible cystoscope. We inserted a guidewire into the ureteral stent before removing it and placed a 16F urethral catheter along the guidewire. We analyzed the difference between two groups including the incidence, the length and the management of urethral stricture and the complexity of urethroplasty if needed. The simple urethroplasty was defined as performing anastomosis after dissection of the bulbar urethral and removing the scar tissue, while the procedure was defined as complex urethroplasty if ancillary procedures, such as separating the corporal bodies and partial pubectomy, was needed.Results:The EER group and SC group had 33 patients and 27 patients, respectively. The mean operation time of EER was (24.5±7.0)minutes and there was no intra-operative complications. Postoperatively, 4 cases of bleeding and 2 cases of UTI were found, which were successfully treated by conservative managements. Twenty-eight out of 33 patients(84.8%) in EER group developed urethral stricture and the mean length of it was (3.10±1.20)cm. However, all patients in SC group developed urethral stricture (100.0%) with the mean stricture length of (3.83±1.18)cm. The difference between two groups in term of the length of stricture was statistically significant ( P=0.026). 24 patients(85.7%) in EER group were treated by urethroplsty, 2 patients(7.1%) with endoscopic urethrotomy and 2 patients (7.1%) with dilation. All were treated with urethroplasty but 2 patients with endoscopic in SC group. In EER group, 8 strictures (33.3%)finished with simple urethroplasty and 16 strictures (66.7%) with complex urethroplasty.While in SC group, 6 strictures(24.0%) completed with simple urethroplasty and 19 strictures (76.0%)with complex urethroplasty. The complexity of urethroplasty performed in EER group was not statistically significant when compared with it in SC group( P=0.538). Conclusions:The procedure of EER with flexible cystoscope is reliable and safe. Most patients with formed urethral stricture after PFUI would be treated with urethroplasty. EER can reduce the urethral stricture formation and may decrease the need of the ancillary procedures during the urethroplasties if needed.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective To observe the effect of pre-intervention with electroacupuncture at Neiguan (PC 6) plusα2-adrenoceptor (α2AR) agonist on peri-operative heart rate variability (HRV).Method A total of 120 patients going to receive lower limb orthopedic surgery were randomized into four groups by using the random number table, namely a control group (group A), an electroacupuncture group (group C), anα2AR agonist group (group D) and an electroacupuncture plus medication group (group N), 30 cases in each group. The indicators of heart rate variability (HRV), including the standard deviation of normal-to-normal (N-N) intervals (SDNN), standard deviation of the average of N-N intervals (SDANN), root mean square successive differences (rMSSD), percentage of adjacent N-N intervals>50 ms apart (pNN50), low-frequency power (LF), high-frequency power (HF), LF/HF and total power (TP) were recorded 1 d prior and 1 d after the operation; meanwhile, the mean arterial pressure (MAP) and heart rate (HR) were recorded before incubation (T0), right after incubation (T1), 5 min after incubation (T2), right afterextubation (T3), 5 min after extubation (T4), 60 min after extubation (T5), and 180 after extubation (T6).Result In group N, the HR and MAP at the other time points were insignificantly different from those at T0 (P>0.05); in group A, the HR and MAP at T1-T6 were significantly different from those at T0 (P<0.05); in group C and D, the HR and MAP at T1-T4 were significantly different from those at T0 (P<0.05); the HR and MAP in group N were significantly lower than those in group A at T1-T6 (P<0.05) and were significantly lower than those in group C and D at T1-T4 (P<0.05); the HR and MAP in group C and D were significantly lower than those in group A at T5 and T6 (P<0.05). In group A, the LF, HF, LF/HF and TP 1 d after the operation were significantly increased compared to those 1 d prior to the operation (P<0.05); in group A and D, the SDNN, SDANN, rMSSD, and pNN501 d after the operation were significantly lower than those 1 d prior to the operation (P<0.05); the LF, HF, LF/HF, and TP in group C, D and N were significantly lower than those in group A 1 d after the operation (P<0.05); the SDNN, SDANN, rMSSD, and pNN50 in group C and N were significantly higher than those in group A and D 1 d after the operation (P<0.05). Conclusion Pre-intervention electroacupuncture plusα2AR agonist can improve the balance of cardiac sympathetic and vagus nerves, and better maintain the peri-operative hemodynamic stability.

Staging of hepatocellular carcinoma (HCC) need to consider tumor factors and functional status of liver,which is different from other solid tumors.Now there are many clinical staging and prognosis systems of HCC.Intermediate stage HCC is commonly occurred at disease diagnosis,with varied clinicopathological charactertics,therapeutic options and survival outcomes of patients.In this review,the definition,current therapeutic strategies,substaging model of intermediatestage HCC and the efficacy of liver resection for patients of intermediate-stage HCC are discussed for further improving feasibility of individualized surgical therapy.

Objective To investigate the overall survival prediction of the Bolondi substaging model for patients in intermediate-stage of Barcelona clinic liver cancer (BCLC) after hepatectomy.Methods The retrospective cohort study was adopted.The clinical data of 343 patients with intermediate-stage hepatocellular carcinoma (HCC) who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University between February 2008 and January 2010 were collected.All the patients received the detailed medical history collection,physical examination,laboratory and imaging examinations after admission,and then hepatectomy was performed according to the results of above examinations.Research methods:(1) patients were allocated into the B1,B2 and B3/4 groups based on the Bolondi's substaging model,and the prognostic analyses among groups were conducted.(2) The related factors affecting the prognosis of patients in the B1 and B2 groups were analyzed.(3) The patients in the B1 and B2 groups were allocated into the 4 groups [patients of B1 group with negative microvascular invasion (MVI) were divided in the M1 group,patients of B1 group with positive MVI in the M2 group,patients of B2 group with negative MVI in the M3 group and patients of B2 group with positive MVI in the M4 group] according to the situations of MVI,and stratified analysis was conducted.Observation indicators:basic clinical and pathological features and survival of patients in the B1,B2 and B3/4 groups were observed.Risk factors analysis affecting the prognosis of patients and stratified analysis of MVI in the B1 and B2 groups were conducted.All the patients were followed up by outpatient examination and telephone interview up to February 2014,and the abdominal ultrasound,liver function and serum alpha-fetoprotein (AFP) tests was performed once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively.The continuous variables and categorical variables were respectively represented as M(Qn) and percentage.The comparisons of continuous variables and categorical variables among groups were analyzed by ANOVA or Kruskal-Wallis test and chi-square test or Fisher exact probability,respectively,and one-way ordinal categorical variables were analyzed by the Kruskal-Wallis test.The survival curve was drawn using the KaplanMeier method.The univariate analysis and multivariate analysis were done using the Log-rank test and COX regression model.Results (1) The basic clinical pathological features:of 343 patients with HCC,143,183 and 17 patients (12 in the B3 substaging and 5 in the B4 substaging) were respectively allocated into the B1,B2 and B3/4 groups.There were statistically significant differences in the age,peritoneal effusion,total bilirubin (TBil),albumin (Alb),alanine transaminase (ALT),prothrombin time (PT),platelet (PLT),alpha-fetoprotein (AFP),extent of liver resection,surgical margin ivasion,tumor diameter,number of tumor,Edmondson-Steiner grade,Up-to-7 score,Up-to-7 standard and Child-pugh score among the 3 groups (F =3.377,NA,11.245,32.616,6.884,11.564,33.100,12.902,NA,NA,239.089,10.357,x2=8.906,F =251.508,x2 =343.000,106.790,P ＜ 0.05).(2) Survival of patients:all the patients were followed up for 2.8-70.8 months with a median time of 38.7 months.The 1-,3-,5-year survival rates and median survival time in the B1,B2 and B3/4 groups were 85.8％,72.8％,52.9％ and 63.2％,47.5％,16.8％ and 45.5％,30.4％,8.4％ and 55.1 months,35.1 months,12.2 months,respectively,showing a statistically significant difference (x2 =22.800,P ＜ 0.05).(3) Risk factors analysis:the results of univariate analysis showed that the peritoneal effusion,Alb,Hb,AFP,esophagogastric varices,surgical margin invasion,tumor diameter,MVI and Edmondson-Steiner grade were related risk factors affecting the prognosis of patients with HCC after hepatectomy [HR =2.04,2.46,2.50,1.78,1.55,3.54,1.71,1.76,1.69,95％ confidence interval (CI):1.13-3.69,1.20-5.02,1.51-4.15,1.29-2.45,1.06-2.25,1.65-7.61,1.23-2.38,1.23-2.51,1.08-2.64,P＜0.05].The results of multivariate analysis showed that the Alb ＜ 35 g/L,Alb ＜ low limit of normal,tumor invading to surgical margin,tumor diameter ＞ 5 cm and positive MVI were independent risk factors affecting the overall survival of patients with HCC after hepatectomy (HR =2.82,2.16,2.93,1.48,1.53,95％ CI:1.37-5.80,1.27-3.69,1.33-6.44,1.05-2.09,1.06-2.22,P＜0.05).(4) There were 61,82,57 and 126 patients in the M1,M2,M3 and M4 groups,and M2 and M3 groups were merged into the M2/3 group because of being similar survival situations of patients.The 1-,3-,5-year survival rates and median survival time in the M1,M2/3,and M4 groups were 90.0％,83.2％,67.7％ and 68.8％,59.9％,41.6％ and 52.7％,42.1％,23.6％ and 69.0 months,49.2 months,24.9 months,respectively,with a statistically significant difference among the 3 groups(x2=20.200,P ＜ 0.05).Conclusions The Bolondi substaging model produces an optimal survival prediction for patients in intermediate stage of BCLC after hepatectomy.The patients in the B1 and B2 substaging have better long-term survival outcomes after hepatectomy.