A "Five-step" System For Preoperative Surgical Decision-making In Gallbladder Cancer

Part1Preoperative prediction of survival benefits in gallbladder cancer after radical resectionObjective Currently, all frequently used staging systems in gallbladder cancer are based on postoperative pathological examinations, such as AJCC and JSBS systerm. In patients undergoing curative operation, there is no effective method to predict survival preoperatively. In this study, we explored (1) the prognostic value of Carbohydrate Antigen19-9(CA19-9) and Carcinoembryonic Antigen (CEA);(2) whether a combined utilization of CA19-9and CEA could give a preoperative prediction of survival in resectable GBC.Method Seventy-three patients who underwent radical resection for gallbladder cancer were included in this study. All patients followed the criterion for radical resection set by NCCN guideline.Results By multivariate analysis, CA19-9elevation (P<0.05) and CEA elevation (P<0.001) were discovered as two individual factors for postoperative survival. By a combined utilization, patients were divided into three groups:patients with elevation of CEA, with or without elevation of CA19-9(Group I), patients with elevation of CA19-9but without CEA (Group II), and patients with non-elevations of either CA19-9or CEA (Group III). The cumulative5-year survival in Group I, II, III was0.0%,14.0%and43.3%, respectively (P<0.05).Conclusions By a combined utilization of CA19-9and CEA, individualized prediction of survival is available in resectable GBC before operation. Extended radical operation should be carefully considered in patients with elevation of CA19-9or CEA. However, in the absence of elevations of tumor biomarkers, RO resection should be struggled for the survival benefis. Part2Preoperative prediction of lymphatic metastasis in gallbladder cancer and a new strategy to complement the present radiological detectionObjective Gallbladder cancer is frequently accompanied with lymphatic metastasis (LM). Unfortunately, by presently used radiological modalities, such as computed tomography (CT), more than half of patients with LM could not be detected preoperatively. We aim to (1) test the present radiological evaluation of LM (2) explore risk factors of LM in gallbladder cancer, and their potential to complement radiological detection.Method Except the criterion used in part1, all patients stage as T1b or above needed to have at least three lymph nodes harvested, according to a general standard for AJCC staging system. At last,63patients were included in this study.Results Only31.3%(10/32) of patients with LM were detected by CT. Through multivariate analysis, two risk factors of LM were discovered as age<60years (OR=6.24, P<0.01) and CA19-9elevation (OR=5.70, P<0.05). By analysis of patients with pathological LM but failed to be detected by CT,81.8%(18/22) of patients had at least one risk factor, including31.3%(10/32) who had the risk factor of age<60years, and37.5%(12/32) who had the risk factor of CA19-9elevation. Besides, among patients with LM (n=32), those whose age were younger than60years (OR=3.41, P<0.05) were more likely to have3or more positive lymph nodes.Conclusion Age<60years and CA19-9elevation could complement radiological detection of LM. Patients aged<60years are at higher risk of multiple positive nodes. Part3Risk factors of disseminated metastasis in gallbladder cancer and an algorithm for choosing patients for staging laparoscopyObjective In operation with curative intent for gallbladder cancer, discovery of disseminated metastasis (peritoneal or hepatic) is not rare. For patients with disseminated metastasis, commonly used laparotomy is of no therapeutic use. In this study, we aimed to (1) explore risk factors of disseminated metastasis (2) build a predictive system for the choice between direct laparotomy and staging laparoscopyMethod:118patients with gallbladder cancer were included, all were found to be resectable at CT imaging.Results:During surgical exploration,22.0%(26/118) of patients were found to have disseminated metastasis, including17.8%(21/118) as peritoneal and4.2%(5/118) as hepatic. Multivariate analysis suggested only two independent risk factors as adjacent organ invasion at CT imaging (OR=4.281, P<0.05) and CA-125elevation (OR=3.472, P<0.05). Patients were divided into three groups by distribution of risk factors. Group Ⅰ: no risk factor; Group Ⅱ, one risk factor; and Group Ⅲ, two risk factors. The incidence of disseminated metastasis was4.1%(2/49) in Group Ⅰ,24.4%(10/41) in Group Ⅱ, and50.0%(14/28) in Group Ⅲ. Comparison of incidence between each two group showed statistical significance.(P<0.05)Conclusion:In radiologically resectable gallbladder cancer, patients with adjacent organ invasion at CT imaging and CA-125elevation are at higher risk of disseminated metastasis. Staging laparoscopy could be more efficient by targeting to patients with risk factors, especially when the two factors coexist. Part4Tumor biomarkers in correcting misdiagnosis of gallbladder cancer:help or misleading?Objective Gallbladder cancer are easily to be misdiagnosed in the following two situations:(1) Gallbladder cancer at early stage misdiagnosed as benign, namely incidental gallbladder cancer (2) Xanthogranulomatous cholecystitis misdiagnosed as maligenant, although it is kind of benign lesion. We aim to explore whether tumor biomarkers could help to correct misdiagnoses in the situations mentioned above.Methods (1) Documents of patients as incidental gallbladder cancer were reviewed, patients needed to have the test of tumor biomarkers tests within half a year before operation. At last eleven patients were included, and compared to78patients with benign gallbladder diseases.(2) Documents of patients suspicious of gallbladder cancer but pathologically confirmed to be Xanthogranulomatous cholecystitis after surgical operations were reviewed.37patients were included.Results (1) Among11patients, only1patient (9.1%) had elevation of CA19-9, while the others had negative CA19-9and CEA results. The median levels of CA19-9in unsuspected gallbladder cancer were similar to those having benign gallbladder diseases (19.9vs16.9), as well as CEA (1.3vs1.6). Comparison between two groups showed no statistical significance (P>0.05).(2)54.1%of cases (20/37) had at least one elevation over the threshold of CA19-9(37IU/L), CEA (5ng/ml), CA12-5(35IU/L), which increased the suspicion of malignancy, and consequently enhanced the difficulty to make right diagnosis of XGC as benign.The presence of common bile duct stone was a contributor for elevation of CA19-9in patients with XGC. However, even in cases without common bile duct stones,42.9%of patients (9/21) had elevations of at least one tumor biomarker. Among them,26.1%of patients (6in21) had elevations of CA19-9, with the maximum of536.29IU/L.Conclusions In the presence of misdiagnosis of incidental gallbladder cancer and Xanthogranulomatous cholecystitis, tumor biomarkers would further mislead surgical-decision making. Part5A "five-step" system for surgical decision-making in gallbladder cancerObjective To build a system for surgical decision-making in gallbladder cancerMethods As a summarization of the previous resultsResultsFive steps were as follows(1) Tumor biomarkers should not be used to assist the judgment for being malignant or benign in gallbladder diseases, especially when incidental gallbladder cancer and Xanthogranulomatous cholecystitis are suspected.(2) In radiologically resectable gallbladder cancer, patients with adjacent organ invasion at CT imaging or CA-125elevation are at higher risk of disseminated metastasis. Direct lapartomy could be used for patients without presence of either factor. When the two factors coexist, staging laparoscopy or further examination is a must.(3) After exclusion of disseminated metastasis, the biopsy of lymph nodes in N2station is recommended before implementation of radical resection. If biopsy proves malignancy, radical resection should be given up. The procedure of biopsy is recommended to be carried out under laparotomy rather than laparoscopy.(4) Extended radical operation should be carefully considered in patients with elevation of CA19-9and CEA. However, in the absence of elevations of tumor biomarkers, RO resection should be struggled considering the survival benefits.(5) Patients with age<60years and CA19-9elevation could were at higher risk of having LM, even when radiological modality failed to prove that. Patients aged <60years are at higher risk of multiple positive nodes.Conclusions This five-step system could assist surgical decision-making in gallbladder cancer. It needs verification in larger population.