Early-stage Gallbladder Carcinoma Research Articles

A nomogram-based model and ultrasonic radiomic features for gallbladder polyp classification.

Gallbladder polyps (GBPs) are relatively common. Many studies have attempted to distinguish between benign and neoplastic GBPs to identify early-stage gallbladder carcinoma. We have established an accurate neoplastic predictive model and evaluated the effectiveness of radiomics in predicting malignancy in patients with GBPs. A total of 503 patients confirmed through postoperative pathology were included in this retrospective study. Clinical information and ultrasonographic findings were retrospectively analyzed. The model was constructed from independent risk factors using Spearman correlation and logistic regression analysis of a training cohort of 250 GBP patients, and its efficacy was verified using an internal validation group of 253 consecutive patients through the receiver operating characteristic curve (ROC). The area of GBPs was delimited manually, and the texture features of ultrasound images were analyzed using correlation and ROC analysis. Independent predictors, including age, gallstones, carcinoembryonic antigen, polyp size, and sessile shape, were incorporated into the nomogram model for the neoplastic potential of GBPs. Compared with other proposed prediction methods, the established nomogram model showed good discrimination ability in the training group (area under the curve [AUC]: 0.865) and validation group (AUC: 0.845). Regarding ultrasonic radiomics, the minimum caliper diameter was identified as the only independent predictor (AUC: 0.841). Our preoperative nomogram model can successfully evaluate the neoplastic potential of GBPs using simple clinical data, and our study verified the use of radiomics in GBP identification, which may be valuable for avoiding unnecessary surgery in patients.

Plasma-derived candidate biomarkers for detection of gallbladder carcinoma

Gallbladder carcinoma (GBC) is a major cancer of the gastrointestinal tract with poor prognosis. Reliable and affordable biomarker-based assays with high sensitivity and specificity for the detection of this cancer are a clinical need. With the aim of studying the potential of the plasma-derived extracellular vesicles (EVs), we carried out quantitative proteomic analysis of the EV proteins, using three types of controls and various stages of the disease, which led to the identification of 86 proteins with altered abundance. These include 29 proteins unique to early stage, 44 unique to the advanced stage and 13 proteins being common to both the stages. Many proteins are functionally relevant to the tumor condition or have been also known to be differentially expressed in GBC tissues. Several of them are also present in the plasma in free state. Clinical verification of three tumor-associated proteins with elevated levels in comparison to all the three control types—5′-nucleotidase isoform 2 (NT5E), aminopeptidase N (ANPEP) and neprilysin (MME) was carried out using individual plasma samples from early or advanced stage GBC. Sensitivity and specificity assessment based on receiver operating characteristic (ROC) analysis indicated a significant association of NT5E and ANPEP with advanced stage GBC and MME with early stage GBC. These and other proteins identified in the study may be potentially useful for developing new diagnostics for GBC.

The utility of screening ultrasound in early diagnosis of gall bladder cancer among high-risk population

Background: Screening has led to reduction in mortality for cancers of the cervix, prostate, and colon. Advanced gall bladder carcinoma (GBC) have a poor prognosis, compared to early-stage GBC. The aim of this study was early detection of GBC by ultrasound screening, in a high-risk population. Data were analyzed to look at the impact of screening on staging, operability, and survival. Materials and Methods: In this prospective study spanning 4 years, 978 high-risk individuals as per defined criteria, were screened by ultrasound of the abdomen. The clinical profile of patients with screened GBC (S-GBC) and clinically evident GBC (C-GBC) was studied in terms of stage of detection, operability, and median overall survival (mOS). Results: Six cases of GBC were detected as S-GBC. These were compared with a control population of 119 GBC cases presenting to the cancer outpatient department (C-GBC) in the same period. It was found that S-GBC patients compared to C-GBC, had early stages of diagnosis (P = 0.001) and all underwent curative radical cholecystectomy compared to only 18.8% in C-GBC cases (P = 0.004). At 2 years follow-up, mOS was not reached for S-GBC patients as all patients were alive, compared to 9 months mOS in C-GBC cases (P

Immunoproteomics approach revealed elevated autoantibody levels against ANXA1 in early stage gallbladder carcinoma

BackgroundEarly diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of ‘tumor-associated antigens (TAAs) that elicit humoral response’ in early stage GBC patients.MethodsTotal protein from pooled tumor tissue of GBC patients (n = 7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n = 11) or gallstone disease (GSD) cases (n = 11) or early stage GBC (Stage I and II) (n = 5) or GBC stage IIIA (n = 9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins.ResultsImage analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p < 0.05). Receiver operating characteristic (ROC) curve analysis for ANXA1 showed an Area under the Curve (AUC) of 0.69, with 41.7% sensitivity against a specificity of 89.9% for early stage GBC. IHC analysis for ANXA1 protein showed ‘high’ expression levels in 72% of GBC cases whereas all the controls showed ‘low’ expression levels.ConclusionsThe study suggests that the ANXA1 autoantibody levels against ANXA1 may be potentially employed for early stage detection of GBC patients. Other proteins could also be explored and verified in a large cohort of clinical samples.

Pathogenesis of gallbladder adenomyomatosis and its relationship with early-stage gallbladder carcinoma: an overview.

The exact pathogenesis of gallbladder adenomyomatosis is still lacking and some controversies over its diagnosis and treatment exist. Originally recognized as a precancerous lesion, adenomyomatosis is currently recognized by recent studies as a benign alteration of the gallbladder that is often associated with cholecystitis and cholecystolithiasis. Gallbladder carcinoma is an extremely malignant disease with a 5-year survival rate of less than 5%. Therefore, it is important to diagnose, differentiate, and confirm the relationship between adenomyomatosis and early-stage gallbladder carcinoma. However, the early clinical symptoms of adenomyomatosis are extremely similar to those of gallbladder stones and cholecystitis, increasing the difficulty to identify and treat this disease. This article summarizes the research progress on gallbladder adenomyomatosis, aiming to improve the understanding of the pathogenesis of adenomyomatosis and further provide insight for its clinical diagnosis and treatment.

Adenomyomatosis Concomitant with Primary Gallbladder Carcinoma.

Some clinicians have proposed a relationship between gallbladder (GB) cancer and adenomyomatosis (ADM) of the gallbladder, although the latter condition is not considered to have malignant potential. We retrospectively reviewed the surgical pathology database of patients who underwent resection for ADM of the gallbladder at our institution from March 2005 to May 2015. In total, 624 patients underwent surgical resection of the gallbladder with Rokitansky-Aschoff sinuses. Of these cases, 93 were pathologically diagnosed with ADM of the gallbladder, with 44 (47.3%) classified macroscopically as fundal-type ADM, 26 (28.0%) as segmental type, and 23 (24.7%) as diffuse-type ADM. In 3 of the 93 (3.2%) resected specimens, early-stage GB carcinoma was detected, although preoperative imaging did not suggest a malignant neoplasm of the gallbladder in any of these patients. GB cancer subsequently developed in the mucosa of the fundal compartment distal to the annular stricture of the segmental-type ADM in 2 of these patients and against the background of the fundal-type ADM in 1 patient. This study revealed the difficulty of early diagnosis of primary GB cancer in the setting of concurrent ADM, and clinicians should be aware of this frequent coexistence.

Prognosis and clinical outcome analysis of 29 cases with T1a unsuspected gallbladder carcinoma

Objective To summarize the clinicopathological features of T1a unsuspected gallbladder carcinoma (UGC), investigate the therapeutic strategy and identify the potential prognostic factors. Methods A retrospective study was carried out on 29 cases diagnosed as T1a UGC during or after Laparoscopic cholecystectomy (LC) from January 2003 to July 2014. The demographic and clinical data were collected and analyzed. Results Of the 29 T1a UGC diagnosed during (n=11) or after (n=18) LC, 26 cases underwent simple LC. 1 case converted to simple open cholecystectomy (OC) because of severe cholecystitis and 1 case underwent additional radiofrequency ablation of gallbladder bed and was diagnosed during LC by frozen section. 1 case underwent radical resection 24 days later. No lymph node metastasis, vascular invasion and perineural invasion were founded in the 29 cases and resection margin was tumor negative. During the study period, 2 patients died. One case died of disseminated metastasis in the abdominal cavity and the other of primary hepatic carcinoma. The 1-, 3-, 5-year accumulative survival rate of the 27 cases after simple cholecystectomy was 100%, 96.2%, 96.2%, and the other two cases with radiofrequency ablation of gallbladder bed and radical resection of UGC both had long-term survival. Conclusion Simple cholecystectomy is appropriate for T1a UGC patients, but the complete resection of the gallbladder is essential for improving the patients' outcome. Key words: Unsuspected gallbladder carcinoma; Early-stage gallbladder carcinoma; Therapy; Laparoscopic cholecystectomy; Prognosis

Laparoscopic Approach for Suspected Early-Stage Gallbladder Carcinoma

To determine the feasibility of the laparoscopic approach for treating suspected early-stage gallbladder carcinoma. Prospective study from a university hospital. From May 10, 2004, to October 9, 2007, the laparoscopic approach was considered for treating 36 patients with suspected gallbladder carcinoma at T2 or less without liver invasion based on the preoperative computed tomographic scan. To further exclude liver invasion, preoperative endoscopic ultrasonography (US) and laparoscopic US were additionally performed. Frozen biopsy was performed after completing the cholecystectomy. If carcinoma was found, laparoscopic lymphadenectomy was performed. Feasibility and operative outcome. Three patients who had liver invasion on endoscopic US underwent open surgery. An additional 3 patients who had liver invasion noted on laparoscopic US had their surgical procedure converted to laparotomy. Finally, 30 patients underwent a laparoscopic procedure. With combined computed tomography, endoscopic US, and laparoscopic US, the negative predictive value for excluding hepatic invasion reached 100%. For the 12 patients who had benign lesions noted on their frozen biopsies, their laparoscopic surgical procedure was completed. The remaining 18 patients who had gallbladder carcinoma underwent additional laparoscopic lymphadenectomy. During laparoscopic lymphadenectomy 1 conversion occurred owing to bleeding, the median operative time was 190 minutes, and the median blood loss was 50 mL. The complication rate was 16.7% and the median postoperative hospital stay was 4 days. After a median follow-up of 27 months, all 18 patients who underwent laparoscopic lymphadenectomy survived without any evidence of recurrence or metastasis. Laparoscopic treatment is feasible and safe in selected patients with early-stage gallbladder carcinoma.

Laparoscopic cholecystectomy for early gallbladder carcinoma: long-term outcome in comparison with conventional open cholecystectomy

The role of laparoscopic surgery for malignant gallbladder tumors remains uncertain. This study compared the surgical results of laparoscopic versus conventional open cholecystectomy for patients with early-stage gallbladder carcinoma and examined the role of laparoscopic surgery for early gallbladder carcinomas. Data for the treatment of gallbladder carcinomas were gathered from Chang Gung Memorial Hospital (Linkou, Taiwan). A retrospective analysis of 40 patients with either stage 0 or stage 1 gallbladder carcinoma was performed. The patients were categorized into two groups on the basis of cholecystectomy procedures. The long-term outcomes for the two groups were compared. During the follow-up period, which ranged from 6.5 to 197.6 months, four patients in the conventional open cholecystectomy group encountered tumor recurrence, and one patient in the laparoscopic cholecystectomy group experienced distant tumor recurrence (p = 0.216). No local port-site tumor recurrence was identified in patients who underwent laparoscopic cholecystectomy. The overall 5-year survival rate in this series was 87.1%. A comparison of survival rates between the two groups demonstrated no significant difference (p = 0.340). The laparoscopic cholecystectomy procedure did not adversely influence the prognosis of patients with early-stage gallbladder carcinomas. Furthermore, meticulous removal of gallbladders during laparoscopic surgery, in which early gallbladder carcinoma can be managed successfully using laparoscopic cholecystectomy, achieved a satisfactory surgical result and a low port-site tumor recurrence rate.

Surgical strategies in patients with gallbladder cancer: Nihilism to optimism

Gallbladder cancer is an aggressive disease with dismal results of surgical treatment and a poor prognosis. However, over the last few decades selected groups have reported improved results with aggressive surgery for gallbladder cancer. Review of recent world literature was done to provide an update on the current concepts of surgical treatment of this disease. Long-term survival is possible in early stage gallbladder carcinoma. Tis and T1a gallbladder carcinoma can be treated with simple cholecystectomy only. However, in T1b and beyond cancers, aggressive surgery (extended cholecystectomy) is important in improving the long-term prognosis. Laparoscopic cholecystectomy should not be performed where there is a high index of suspicion of malignancy due to the frequent association with factors (such as gallbladder perforation and bile spill) which may lead to implantation of cancer cells and dissemination. Surgical resection for advanced carcinoma gallbladder is recommended only if a potentially curative R0 resection is possible. Aggressive surgery with vascular and multivisceral resection has been shown to be feasible albeit with an increase in mortality and morbidity. However, the true benefit of these radical resections is yet to be realized, as the actual number of long-term survivors of advanced gallbladder carcinoma is few. Surgery for gallbladder carcinoma, like other malignancies, has the potential to be curative only in local or regional disease. Pattern of loco-regional spread of disease dictates the surgical procedure. Radical surgery improves survival in early gallbladder carcinoma. The long-term benefit of aggressive surgery for advanced disease is unclear and may be offset by the high mortality and morbidity.

Value of ultrasonography for diagnosis of early-stage gallbladder carcinoma

目的 探讨早期胆囊癌的超声特征和临床应用价值.方法对经手术病理证实的16例早期胆囊癌与超声结果进行了回顾性分析.结果超声图像分为二型:壁增厚型、黏膜隆起型.同时可发现胆结石征象.结论超声和术中探查是发现早期胆囊癌的主要方法,结合彩色多普勒检查可提高早期胆囊癌的诊断。

Carcinoma of the gallbladder: imaging features with surgical correlation.

common malignant tumor of the biliary tract and the fifth most common gastrointestinal malignancy in the alimentary tract after colorectal, pancreatic, gastric, and esophageal carcinomas. Earlystage gallbladder carcinoma is difficult to detect and is often an incidental finding on sonograms or CT scans. In addition. gallbladder carcinoma is not always detected during laparotomy or during videoscopic surgery and may be unrecognized until histologic examination has been performed. The prognosis of gallbladder carcinoma is still poor and radical surgical resection is, so far, the only potentially curative treatment. Determination of the best therapeutic option requires accurate tumor staging. The aim of this pictorial essay was to present the imaging features of gallbladder carcinoma at initial presentation and correlate the sonographic, CT, and MR imaging appearances of gallbladder carcinoma with surgical findings. The advantages and limitations of each technique for the diagnosis of gallbladder carcinoma and follow-up of patients who had surgery will be discussed.