Resection For Gallbladder Cancer Research Articles

Progress and controversy in minimally invasive approach to radical cholecystectomy for gallbladder cancer

Surgical treatment is one of the most important forms of treatment in patients with gallbladder cancer. With the development of minimally invasive technology, the feasibility, safety and efficacy of minimally invasive approaches such as laparoscopic or robotic-assisted radical cholecystectomy for gallbladder cancer have received continuous attention.For patients with an early T-stage (Tis or T1a), laparoscopic simple cholecystectomy is safe and economical, with a good prognosis for postoperative patients, and it has been widely accepted and performed. Radical resection of advanced gallbladder cancer requires resection of the gallbladder, its liver bed, and other neighboring invaded organs, as well as clearance of regional lymph nodes, which requires experienced gallbladder cancer treatment teams to strictly grasp the indications, select appropriate patients, and formulate a good surgical strategy to ensure the therapeutic effect. Meanwhile, robot-assisted radical resection for gallbladder cancer has been performed in a few centers and shows good clinical potential, but more high-quality studies are needed to further evaluate its value in gallbladder cancer treatment.

The prognostic value of combined preoperative PLR and CA19-9 in patients with resectable gallbladder cancer.

The platelet to lymphocyte ratio (PLR) is the marker of host inflammation and it is a potential significant prognostic indicator in various different tumors. The serum carbohydrate antigen 19-9 (CA19-9) is a tumor-associated antigen and it is associated with poor prognosis of gallbladder cancer (GBC). We aimed to analyze the prognostic value of the combination of preoperative PLR and CA19-9 in patients with GBC. A total of 287 GBC patients who underwent curative surgery in our institution was included. To analyze the relationship between PLR and CA19-9 and clinicopathological features. A receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for PLR and CA19-9. The Kaplan-Meier method was used to estimate the overall survival (OS). Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. The cutoff values of 146.82 and 36.32U/ml defined as high PLR and high CA19-9, respectively. Furthermore, survival analysis showed that patients with PLR > 146.82 and CA19-9 > 36.32 U/ml had a worse prognosis than patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml, respectively. The multivariate analysis demonstrated that PLR (hazard ratio (HR) = 1.863, 95% CI: 1.366-2.542, P < 0.001) and CA19-9 (HR = 1.412, 95% CI: 1.021-1.952, P = 0.037) were independent prognostic factors in the GBC patients. When we combined these two parameters, the area under the ROC curve increased from 0.624 (PLR) and 0.661 (CA19-9) to 0.711. In addition, the 1-, 3-, and 5-year OS of group A (patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml), group B (patients with either of PLR > 146.82 or CA19-9 > 36.32 U/ml) and group C (patients with PLR > 146.82 and CA19-9 > 36.32 U/ml) were 83.6%, 58.6%, 22.5%, 52.4%, 19.5%, 11.5%, and 42.3%, 11.9%, 0%, respectively. The preoperative PLR and serum CA19-9 are associated with prognosis of patients with GBC. The combination of PLR and CA19-9 may serve as a significant prognostic biomarker for GBC patients superior to either PLR or CA19-9 alone.

Expert consensus on the laparoscopic radical resection of gallbladder cancer

The incidence of gallbladder cancer has been increasing. Radial resection is still the most promising curable treatment for patients with gallbladder cancer. Although the techniques required for laparoscopic radical resection of gallbladder cancer have matured, the number of reports is also on the rise, and laparoscopic radical resection of gallbladder cancer is still controversial. To standardize laparoscopic radical resection of gallbladder cancer, the Biliary Surgery Branch, Chinese Society of Surgery, Chinese Medical Association, together with the Chinese Medical Doctor Association in Chinese Committee of Biliary Surgeons, gathered experts to formulate recommendations and consensus on laparoscopic radical resection of gallbladder cancer. This consensus includes several parts: safety, preoperative evaluation, indications, surgical team, positioning of patient and trocars, intraoperative frozen examination, lymph node dissection, liver resection,bile duct resection, etc. Furthermore, suggestions on the principle of treatment, surgical procedures, and precautions were also provided for patients with delayed diagnoses of gallbladder cancer undergoing resection. This consensus aims to offer valuable suggestions for the standardization of laparoscopic radical resection of gallbladder cancer.

Development of new platforms for predicting early recurrence and survival in resected gallbladder cancer

Development of new platforms for predicting early recurrence and survival in resected gallbladder cancer

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis.

Gallbladder cancer is the most common malignancy of the biliary tract. Neoadjuvant chemotherapy (NACT) has improved overall survival by enabling R0 resection. Currently, there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer. As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients, we examined American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to determine if there was higher morbidity among the neoadjuvant group within the 30-day post-operative period. We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity. To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery. A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity (bile leak, infection rate, rate of converting to open surgery, etc.) compared to the group who only had surgery. To calculate the odds ratio for the primary and secondary outcomes, a crude logistic regression was performed. Of the 452 patients, 52 patients received NACT prior to surgery. There were no statistically significant differences in the odds of morbidity between the two groups, including bile leak [odds ratio (OR), 0.69; 95% confidence interval (95%CI): 0.16-2.10; P = 0.55], superficial wound infection (OR, 0.58; 95%CI: 0.03-3.02; P = 0.61), and organ space wound infection (OR, 0.63; 95%CI: 0.18-1.63; P = 0.61). There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

Preoperative risk factors related to relapse-free survival after R0 resection of gallbladder cancer.

566 Background: Gallbladder (GB) cancer shows high prevalence in South Korea, and tends to be fatal. In surgically fit patients, radical resection aiming R0 margin combined with lymphadenectomy is the mainstay of curative-intent therapy. In spite of R0 resection, however, high recurrence rate is observed in GB cancer, demanding a need to find out risk factors related to recurrence after surgery. Methods: This is a single center, retrospective cohort study conducted on 148 patients with GB cancer who underwent R0 resection between January 1st, 2014 and December 31st, 2019. Several variables were analyzed with statistical tools to identify risk factors related to prognosis. Relapse free survival (RFS), defined as time from treatment of disease to any event, was analyzed with Cox regression analysis. Results: Based on statistical analysis, risk factors related to RFS were age over 65 (hazard ratio [HR] 3.82, 95% confidence interval [CI] 1.71 – 8.56, p= .001), glycated hemoglobin (HbA1c) level more than 6.5% (HR 2.72, 95% CI 1.31 – 5.66, p=0.007), surgical T stage more than T3 (HR 5.60, 95% CI 3.05 – 10.25, p&lt;0.001), surgical N stage more than N1 (HR 4.07, 95% CI 2.25 – 7.36, p&lt;0.001), pathologic differentiation of moderate or poor differentiation (HR 2.80, 95% CI 1.46 – 5.37, p=0.002), reversed albumin-globulin ratio (HR 0.16, 95% CI 0.06 – 0.40, p&lt;0.001), and high gamma glutamyl peptidase (GGT) level (HR 1.00, 95% CI 1.00 – 1.00, p&lt;0.001). Conclusions: Advanced pathologic stage and high inflammatory marker levels, reflecting high tumor burden, were related with poor surgical outcome. Interestingly, high HbA1c level was related to reduced RFS as well. In conclusion, active screening for early detection, reducing inflammatory conditions, and managing diabetes might enhance RFS after R0 resection of GB cancer. [Table: see text]

Role of routine frozen biopsy of cystic duct margin in resectable gallbladder cancer without jaundice

Role of routine frozen biopsy of cystic duct margin in resectable gallbladder cancer without jaundice

Perioperative outcomes of robotic radical resection for gallbladder cancer: a single-center case series

Perioperative outcomes of robotic radical resection for gallbladder cancer: a single-center case series

Minimally invasive (MIS) radical cholecystectomy is a feasible approach for resectable gallbladder cancer

Minimally invasive (MIS) radical cholecystectomy is a feasible approach for resectable gallbladder cancer

Effects of Cystic Duct Margin Involvement on the Survival Rates of Patients With Gallbladder Cancer: A Propensity Score-Matched Case-Control Study.

Background In gallbladder cancer (GBC), extrahepatic bile duct (EHBD) resection is selectively performed if gross direct extension or microscopic involvement of the cystic duct margin (CDM) is detected. Although CDMis usually sent for frozen biopsy intraoperatively in most centers, there are no studies regarding the routine use of CDM frozen biopsy irrespective of the tumor location and paucity of literature regarding the impact ofCDM status on recurrence-free and overall survival inGBC. The presence of obstructive jaundice in GBC usually indicates the involvement of EHBD or cystic duct-bile duct junction. The present study aimed to analyze the necessity of routineCDM frozen biopsy inpatients with resectable GBC withoutjaundice, regardless of the tumor location. The impact of positive CDM on survival was also evaluated. Methods This retrospective observational case-control study was conducted from May 2009 to March 2021 and included 105 patients with resectable GBC without macroscopic EHBD infiltration andjaundice. Patients were divided into CDM-negative (n=91) and CDM-positive (n=14) groups. Propensity score matchingwas performed for variables such asperformance status, tumor size, tumor-node-metastasis (TNM) stage, and adjuvant chemotherapy. After propensity score matching, 27 patients (CDM-negative=13, CDM-positive=14) were included. The primary outcome was to analyze the role of routine CDM frozen biopsy regardless of tumor location, and secondary outcomes were to study the impact of positive CDM status on survival andevaluate predictive factors for CDM positivity. A subgroup analysis was conducted to assess clinicopathologic characteristics and outcomes of the anatomical location of the tumor. Results Of 105 patients, 91 had negative CDM, and 14 had positive CDM. Among 14 patients with positive CDM, only one patient had a tumor in the fundus/body, and the remaining had a tumor involving the neck. All CDM-positive patients underwent bile duct excision with hepaticojejunostomy. Common bile duct (CBD) involvement was present in 50% of patients with positive CDM in the final histopathological examination. In the matched population, patients with positive CDM had a significantly higher rate of neck tumors (p=0.001). Recurrence-free survival (24 vs. 12 months, p=0.30) and overall survival (24.5 vs. 20 months, p=0.417) were comparable between CDM-negative and CDM-positive groups, respectively. On multivariate analysis, preoperative and intraoperative tumor location were independent predictive factors for CDM positivity. On subgroup analysis, 30 patients had tumor involving the neck of the gallbladder, and the remaining 75 had at the fundus and body of the gallbladder. Neck tumors had inferior recurrence-free survival (17 vs. 30 months, p=0.012) and overall survival (24 vs. 36 months, p=0.048) compared to non-neck tumors. Conclusions Routine use of CDM frozen analysis in patients with resectable GBC without jaundice, regardless of tumor location, can be avoided. Itcan be selectively preferred in patients with GBC involving the neck since tumor location is found to be an independent predictive factorfor CDM positivity. Positive CDM has comparable survival outcomes to negative CDM, providing a similarR0 resection rate and tumor stage.However, neck tumors have aworse prognosis than non-neck tumors.

166P Preoperative risk factors strongly related to early recurrence after R0 resection of gallbladder cancer

166P Preoperative risk factors strongly related to early recurrence after R0 resection of gallbladder cancer

Textbook outcomes in liver surgery for gallbladder cancer patients treated with curative-intent resection: a multicenter observational study.

Cholecystectomy, hepatectomy, and lymphadenectomy are recommended as the curative treatment for resectable gallbladder cancer (GBC). Textbook outcomes in liver surgery (TOLS) is a novel composite measure that has been defined by expert consensus to represent the optimal postoperative course after hepatectomy. This study aimed to determine the incidence of TOLS and the independent predictors associated with TOLS after curative-intent resection in GBC patients. All consecutive GBC patients who underwent curative-intent resection between 2014 and 2020 were enrolled from a multicenter database from 11 hospitals as the training and the internal testing cohorts, and Southwest Hospital as the external testing cohort. TOLS was defined as no intraoperative grade greater than or equal to 2 incidents, no grade B/C postoperative bile leaks, no postoperative grade B/C liver failure, no 90-day postoperative major morbidity, no 90-day readmission, no 90-day mortality after hospital discharge, and R0 resection. Independent predictors of TOLS were identified using logistic regression and were used to construct the nomogram. The predictive performance was assessed using the area under the curve and calibration curves. TOLS was achieved in 168 patients (54.4%) and 74 patients (57.8%) from the training and internal testing cohorts, and the external testing cohort, respectively. On multivariate analyses, age less than or equal to 70 years, absence of preoperative jaundice (total bilirubin≤3mg/dl), T1 stage, N0 stage, wedge hepatectomy, and no neoadjuvant therapy were independently associated with TOLS. The nomogram that incorporated these predictors demonstrated excellent calibration and good performance in both the training and external testing cohorts (area under the curve: 0.741 and 0.726). TOLS was only achieved in approximately half of GBC patients treated with curative-intent resection, and the constructed nomogram predicted TOLS accurately.

Incidence of synchronous and metachronous peritoneal metastases for gallblader cancer: A single-center cohort analysis.

e16191 Background: The impact of synchronous and metachronous peritoneal metastases (s-pm, m-pm) on survival after curative resection for gallbladder cancer (GBCa) is poorly studied. The anatomy of the gallbladder and its proximity to the liver as well as to the peritoneum has already been included in the 8th edition of the American Joint Committee on Cancer staging system for gallbladder cancer with regard to the tumor location (peritoneal vs. hepatic). However, studies regarding the tumor location and differentiating the impact of peritoneal metastases are needed. Methods: At the Charité - Universitätsmedizin Berlin, a total of 1979 patients with the general diagnosis of cholangiocellular carcinoma were discussed in interdisciplinary tumor conferences from 2010 to 2022. Results: GBCa was present in 316 cases indicating resection for 168 patients. Out of these, 123 patients ultimately underwent curative resection, whereas 45 patients were found to be inoperable due to advanced tumor disease intraoperatively. The 123 curative resections included limited s-pm for seven patients diagnosed incidentally. Here s-pm were evident across all T stages, with one T1V0R0 and one T2V0R1 stage each, T3V1R0 twice, and T3Pn1R1 and T4Pn1R1 once each. Postoperative complications occurred in three of these seven patients (according to Clavien-Dindo): two grade 1; and only one patient grade 3a, requiring a CT drainage. Metachronous metastases, diagnosed in eleven patients after 16.9 months on average with a mean overall survival (OS) of 9.18 months, showed no postoperative complications after the initial surgery. Here T2-status was present in six patients, T3-status in four patients (three T2V0, three T3V0). Complete radical resection (R0) was achieved in six patients, while R1 was recorded in three patients. Furthermore, five patients showed simultaneous hepatic metastases and one of them in parallel osseous metastases. While no neoadjuvant oncologic therapy was performed in any of these eleven patients, adjuvant therapy was applied in nine patients prior to the diagnosis of m-pm. Again, a total of five patients received palliative therapy after diagnosis of m-pm. Nevertheless, four patients underwent reoperation; two cases were treated with cytoreductive surgery including multivisceral resections, while one patient underwent PIPAC twice as an individual tumor approach; the fourth patient underwent surgical exploration for ascites drainage placement. Conclusions: The primary aim regarding the seven s-pm patients was immediate postoperative surgical outcome without complications (&gt;3a according to Clavien-Dindo) and was feasible, regarding the prognostic impact of s-pm for surgical resectability; curative resection might be an option. The primary aim for m-pm was OS, while promising outcomes were shown in this study.

Preemptive resection of choledochal cyst during redo resection of gallbladder cancer following laparoscopic cholecystectomy

Preemptive resection of choledochal cyst during redo resection of gallbladder cancer following laparoscopic cholecystectomy

Gallbladder cancer: current and future treatment options.

Surgery remains the preferred treatment option for early-stage gallbladder cancer (GBC). According to the anatomical position of the primary tumor, accurate preoperative stage and strict control of surgical indications, appropriate surgical strategies are selected to achieve the optimal surgical effect. However, most patients have already been at the locally advanced stage or the tumor has metastasized at the initial diagnosis. The postoperative recurrence rate and 5-year survival rate remain unsatisfactory even after radical resection for gallbladder cancer. Hence, there is an urgent need for more treatment options, such as neoadjuvant therapy, postoperative adjuvant therapy and first-line and second-line treatments of local progression and metastasis, in the whole-course treatment management of gallbladder cancer patients. In recent years, the application of molecular targeted drugs and immunotherapy has brought greater hope and broader prospects for the treatment of gallbladder cancer, but their effects in improving the prognosis of patients still lack sufficient evidence-based medicine evidence, so many problems should be addressed by further research. Based on the latest progress in gallbladder cancer research, this review systematically analyzes the treatment trends of gallbladder cancer.

Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer.

Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression. We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually. The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression. This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

Adjuvant chemoradiotherapy in resected gallbladder cancer: A SEER-based study

BackgroundThe prognosis of gallbladder cancer (GBC) is dismal. This study aimed to compare the outcomes of adjuvant chemoradiotherapy (ACR) with those of surgery alone (S) and adjuvant chemotherapy (AC). MethodThe Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with GBC and undergoing surgery between 2004 and 2015. The patients were divided into the S, AC, and ACR groups according to their treatment. Categorical variables were compared by Pearson’s chi-square test, and a 1:1:1 propensity score matching analysis (PSM) was performed. Overall survival was assessed by Kaplan-Meier curves with log-rank tests. Subgroup analyses were conducted. ResultA total of 5451 patients were identified in the SEER database. After PSM, the two-year survival among patients who received S, AC, and ACR was 36%, 39%, and 45%, respectively. ACR was associated with improved two-year survival (p < 0.001), while the survival rates were similar in the AC and S groups (p = 0.127) but better in the ACR group than in the AC group (p = 0.012). Subgroup analyses indicated that while the two-year survival rates did not differ significantly in stage II GBC patients between the groups (all p > 0.05), ACR was associated with significantly improved two-year survival in stage Ⅲa (p = 0.008), Ⅲb (p < 0.001), and Ⅳb (p < 0.001) GBC patients. ConclusionThe combination of surgery and ACR as the treatment modality provided greater survival benefits for GBC patients, particularly for those with advanced tumor staging.

Short-term efficacy of cholecystectomy plus bile duct T-tube drainage or choledochojejunostomy in the treatment of gallbladder cancer and its effects on median survival time and postoperative complications.

To explore the short-term efficacy of cholecystectomy plus bile duct T-tube drainage or choledochojejunostomy (CJ) in the treatment of gallbladder cancer (GC) and its effects on the median survival time and postoperative complications. The clinical data of 121 patients who underwent laparoscopic cholecystectomy (LC) in department of hepatobiliary surgery of the hospital from January 2018 to December 2018 were retrospectively analyzed. According to the adjuvant treatment methods, the patients were divided into 2 groups: the control group (n = 61, LC + bile duct T-tube drainage) and experimental group (n = 60, LC + CJ). The perioperative indicators, short-term efficacy, median survival time, postoperative complications and immune stress response were compared between the 2 groups of patients before and after propensity score matching. The surgical time, postoperative anal first exhaust time, and intraoperative blood loss in the experimental group were no different from those in the control group (P > .05), but the hospital stay was shorter than that in the control group (P < .05). There was no difference in the effective rate of treatment and median survival time between the 2 groups (P > .05). The total incidence rate of complications in the experimental group at 14 days after surgery was lower than that in the control group (P < .05). Day 3 after surgery, the levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) of the experimental group were higher than those of the control group (P < .05), while the level of C-reactive protein (CRP) was lower than that of the control group (P < .05). Compared with bile duct T-tube drainage, LC + CJ in the treatment of GC can better shorten the postoperative hospital stay and reduce the postoperative complications and immune stress response, but and the median survival time of the 2 is similar, which can be promoted in clinical practice.

Afatinib in combination with GEMOX chemotherapy as the adjuvant treatment in patients with ErbB pathway mutated, resectable gallbladder cancer: study protocol for a ctDNA-based, multicentre, open-label, randomised, controlled, phase II trial

IntroductionGallbladder cancer (GBC) is an aggressive type of digestive system cancer with a dismal outcome. Given the lack of effective treatment options, the disease rapidly reoccurs and 5-year survival rate...

Introducer-assisted endoscopic transpapillary gallbladder biopsy for indeterminate gallbladder fundal wall thickness.

Endoscopic transpapillary gallbladder biopsy (ET-GBBx) remains challenging; therefore, there is no recommendation for the histological examination of patients with resectable gallbladder cancer [1] [2]. Endoscopic introducer-assisted procedures recently emerged for pancreatico-biliary interventions [3]. This article describes the use of introducer-assisted ET-GBBx for indeterminate gallbladder fundal wall thickening.