Laparoscopic cholecystectomy and gallbladder cancer

Heightened awareness of the possible presence of gallbladder cancer (GBC) and the knowledge of appropriate management are important for surgeons practising laparoscopic cholecystectomy (LC). Long-term effects of initial LC versus open cholecystectomy (OC) on the prognosis of patients with GBC remain undefined. Patients who are suspected to have GBC should not undergo LC, since it is advantageous to perform the en-bloc radical surgery at the initial operation. Since preoperative diagnosis of early GBC is difficult, preventive measures, such as preventing bile spillage and bagging the gallbladder should be applied for every LC. Many port-site recurrences (PSR) have been reported after LC, but the incidence of wound recurrence is not higher than after OC. No radical procedure is required after postoperative diagnosis of incidental pT1a GBC. It is unclear if patients with pT1b GBC require extended cholecystectomy. In pT2 GBC, patients should have radical surgery (atypical or segmental liver resection and lymphadenectomy). In advanced GBC (pT3 and pT4), radical surgery can cure only a small subset of patients, if any. Additional port-site excision is recommended, but the effectiveness of such measure is debated.     

Comparison of Clinical Outcomes of Incidental and Non-Incidental Gallbladder Cancers: A Single-Center Cross-Sectional Study

Background: Gallbladder cancer (GBC) is a rare malignancy characterized by high invasiveness and poorsurvival. In a nation-wide cancer survey, the age-standardized incidence rate of GBC was the highest in JejuIsland compared to 15 other provinces in Korea. The purpose of this study was to compare the clinical outcomesof GBC according to the nature of diagnosis, that is, incidental versus non-incidental. Materials and Methods:Consecutive patients who were newly diagnosed with GBC at the Digestive Disease Center and Department ofInternal Medicine, Cheju Halla General Hospital, between November 2008 and November 2011, were enrolledand divided into 2 groups: incidental gallbladder cancer (IGBC) and non-incidental gallbladder cancer (NIGBC).Clinical outcomes were retrospectively compared between the two groups. Results: Seventy-nine patientswere enrolled and analyzed in our study. Thirty-three (41.8%) and 46 (58.2%) were identified as IGBC andNIGBC, respectively. The proportions of patients with gallstone disease, gallbladder polyp, and cholecystectomywere significantly different between the two groups. Additionally, the median survival rate was significantlyhigher for patients with IGBC than for those with NIGBC (11.4, 95% confidence interval, 5.6-13.7 vs 4.0, 95%confidence interval 3.03-5.96 months; p=0.01) during a median follow-up period of 5.7 months. Conclusions:Patients with IGBC showed better clinical prognosis than those with NIGBC. Therefore, patients with gallstonedisease or gallbladder polyps, major predictive risk factors for IGBC, should undergo advanced work-up forchelecystectomy.     

Unsuspected gallbladder cancer diagnosed during or after laparoscopic cholecystectomy

BACKGROUND: The long-term prognosis of laparoscopic cholecystectomy (LC) for patients with unsuspected gallbladder carcinoma (GBC) remains unclear. We investigated retrospectively the role of examination of frozen sections and the prognosis of patients with unsuspected GBC detected during or after LC. METHODS: LC was performed on 1,793 consecutive patients. If a suspicious lesion was found, intraoperative frozen section examination was performed. RESULTS: Of all these patients, 38 (2.1%) were histopathologically diagnosed as having a GBC during (28) or after LC (10). The tumor stages of the 28 diagnosed during LC were: pT1a (17), pT1b (2), pT2 (8), and pT3 (1). The sensitivity and specificity of intraoperative frozen section examination were 90 and 100%, respectively. On the other hand, those 10 cases diagnosed after LC had pT1a (1) and pT2 (9) tumors. Survival rates were not significantly affected by whether the patient was diagnosed with GBC during or after LC. CONCLUSIONS: The survival with unsuspected GBC was related to stage and it was confirmed that a carefully performed LC is adequate treatment for Stage 1A and B cancer. The LC procedure does not adversely affect the prognosis of unsuspected GBC, regardless of whether it is detected during or after LC.     

Selective or Routine Histology of Cholecystectomy Specimens for Diagnosing Incidental Carcinoma of Gallbladder and Correlation with Careful Intraoperative Macroscopic Examination? A Systematic Review

Background: Selective or Routine histology of cholecystectomy specimens for benign gallbladder disease has always been a matter of debate because of the low prevalence and bad prognosis associated with gall bladder carcinoma. The objective of this study is to ascertain whether selective histology can be preferred over Routine histology without any harm. Methods: This systematic review is conducted according to PRISMA’s checklist; relevant articles were searched in the database until September 1 2020 in PubMed, Scopus, Science Direct, and Web of Science databases, manually, with search queries and without date restrictions. Studies included in this systematic review involved patients who underwent cholecystectomy for benign gallbladder disease and were diagnosed with gallbladder carcinoma incidentally either after selective or routine histology of the gallbladder. Results: A total of 24 routine or selective histology recommending studies were selected for the systematic review after following the inclusion and exclusion criteria. These studies comprised 77,213 numbers of patients and 486 numbers of Malignancies. These studies correlate the number of IGBC diagnosed histologically with the number of IGBC’s that were suspected by the surgeons intraoperative by macroscopy. Routine recommending studies show a significant number of IGBC diagnosed histologically as missed by surgeons whereas the selective recommending studies show most of the histologically diagnosed IGBC already suspected by the surgeons intraoperative. When comparing the macroscopic details of the IGBC’s between routine and selective studies, we found that there was significant overlap. Most of the findings missed by the surgeons as suspicious in routine studies were suspected by the surgeons involved in selective histology recommending studies. Thereby, favouring selective histology and emphasizing the need for careful intraoperative macroscopy for suspecting IGBC. Conclusion: Selective Histological examination of cholecystectomy specimens can be preferred if a careful intraoperative macroscopic examination is done and patient risk factors are taken into consideration.     

Incidental gall bladder cancers: Are they truly incidental?

AIM: To seek and analyze features suggestive of gallbladder cancer (GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC (IGBC).METHODS: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period (2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect.RESULTS: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, difficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42 (53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis.CONCLUSION: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality.     

Clinicopathological Study of Gall Bladder Carcinoma with Special Reference to Gallstones: Our 8-year Experience from Eastern India

Gallbladder carcinoma (GBC) is the commonest cancer of the biliary tree and the most frequent cause of deathfrom biliary malignancies. The incidence of GBC shows prominent geographic, age, race, and gender-relateddifferences and is 4-7 times higher in patients with gallstones. This prompted us to study the clinicopathologicalaspects of the disease and the incidence of gallstones in gallbladder carcinoma patients, in this part of India. Inthis, combined retrospective (Jan 2004-March 2010) and prospective study (April 2010-Dec 2011) of eight years,198 patients of gallbladder carcinoma (50 males and 148 females), (range 28-82 years; mean 55 years) were studied.Most of the patients were poor and presented with abdominal pain and mass, with abnormal lab parameters.Gallstones were present in 86% of patients. Surgical exploration was performed in 130, with gallbladder resectionin 60 (including 7 incidental GBC). Adenocarcinoma (87.7%) was the commonest histological type. The studyindicates that GBC is common in our scenario. It is a disease of elderly females, has a strong association withgallstones and every cholecystectomy specimen should be examined histopathologically.     

Incidental gallbladder cancer: what management?

Gallbladder cancer (GBC) represents 3.8% of all gastrointestinal cancers and usually known to be of a poor prognosis. In 0.2–2.9% of cases, this cancer is found in cholecystectomy specimens. A better understanding of spread mode of this tumor helps a better surgical management. The aim of the present review is to underline the management of GBC based on the comprehension of risk factors and anatomic features. A Medline, PubMed database search was performed to identify articles published from 2000 to 2011 using the keywords ‘carcinoma of gallbladder’, ‘incidental gallbladder cancer’, ‘gallbladder neoplasm’ and ‘cholecystectomy’. Some pathological situations such as chronic lithiasis and biliopancreatic junction abnormalities have been clearly identified as predisposing to GBC. Laparoscopy increases peritoneal and parietal tumor dissemination, thus, it should not be performed when GBC is suspected. Most determinant prognostic factors are nodal, perineural and venous involvement, invasion of the cystic duct and the tumor differentiation. The simple cholecystectomy is sufficient for tumors classified as T1a; for other cancers exceeding the muscularis, radical re-resection is required due to the high risk of recurrence. This aggressive surgery improved the overall survival of patients. There is still no standard adjuvant treatment; patients should be included in prospective trials.     

Incidental carcinoma of the gallbladder.

Incidental gallbladder carcinoma (GBC) is a difficult management issue as there are no established guidelines. Laparoscopic cholecystectomy is associated with increased dissemination of the tumour cells (both in the peritoneal cavity and port sites). Depth of tumour invasion (T stage) and positive surgical margins are the most important prognostic factors, although tumour differentiation, lymphatic, perineural and vascular invasion may also affect the outcome. Simple cholecystectomy is adequate for mucosal (T1a) lesions only. For T1b tumours port site/wound excision with second radical operation (probably extended cholecystectomy -- wedge liver excision with regional lymphadenectomy) should be advised. T2 tumours should be treated with second radical operation (extended cholecystectomy or excision of medial liver segments 4b and 5 or 4, 5 and 8 with regional lymphadenectomy with or without excision of the extra-hepatic bile duct). Few T3 tumours can be cured and in some survival time may be prolonged by a second radical operation. More extensive liver resection (segments 4b and 5 or segments 4, 5 and 8) with regional lymphadenectomy with excision of the extra-hepatic bile duct should be advised. A second radical operation may palliate some T4 tumours. In the absence of extensive nodal disease, this operation may prolong the survival time. Excision of the extra-hepatic bile duct should be undertaken whenever the tumour involves the cystic duct margin or the extra-hepatic biliary tree. Epidemiology, risk factors, aetiopathogenesis and the modes of spread of GBC are discussed in relation to appropriateness of the second radical operation. Indications, types and role of the second radical operation are discussed.     

Gallbladder cancer: Past,present and an uncertain future

Although gallbladder cancer (GBC) is the most common malignancy of the biliary tract, its relatively low incidence and confounding symptomatology result in advanced disease at the time presentation, contributing to the poor prognosis and decreased survival associated with this disease. It is therefore increasingly important to understand its pathogenesis and risk factors to allow for the earliest possible diagnosis. To date, gallbladder cancer is poorly understood compared to other malignancies, and is still most commonly discovered incidentally after cholecystectomy. Moreover, while much is known about biliary neoplasms as a whole, understanding the clinical and molecular nuances of GBC as a separate disease process will prove a cornerstone in the development of early intervention, potential screening and overall more effective treatment strategies.The present work reviews the most current understanding of the pathogenesis, diagnosis, staging and natural history of GBC, with additional focus on surgical treatment. Further, review of current adjuvant therapies for unresectable and advanced disease as well as prognostic factors provide fertile ground for the development of future studies which will hopefully improve treatment outcomes and affect overall survival for this highly morbid, poorly understood malignancy.     

The surgical management of incidental gallbladder carcinoma.

AIMS: To report the surgical management of carcinoma of the gallbladder. METHODS: A retrospective study in 65 patients who underwent simple (SC) or extended (EC) cholecystectomy for gallbladder carcinoma. RESULTS: 28 patients underwent extended cholecystectomy (EC) and 37 had simple cholecystectomy (SC). The multivariate analysis showed that lymph-node status (positive vs negative, p=0.001, Hazard Ratio [HR]:14.2, 95% Confidence Interval [CI]:3.1-62.8) and type of surgery (SC vs EC, p=0.01, HR:10.2, 95% CI:1.7-62.8) were the most important prognostic factors related to death. This analysis indicated that EC in those with pT(2) or pT(3) was associated with a reduce hazard of death by 90% in the follow-up period. CONCLUSIONS: In gallbladder cancer patients who diagnose after simple cholecystectomy, those with pT(1) with clear margins need no further surgery. In patients with pT(2) or pT(3) incidental carcinoma, the completion radical re-operation is the only chance for long-term survival.     

胆囊癌中基质金属蛋白酶9表达与淋巴结转移及预后的关系

目的　研究胆囊癌中基质金属蛋白酶 9(MMP 9)表达的情况 ,探讨MMP 9表达的临床意义。方法　应用免疫组化Envision二步法测定 4 6例胆囊癌 (gallbladdercarcinomaGBC)和 12例慢性结石性胆囊炎、3例胆囊腺瘤中MMP 9表达。结果　MMP 9在胆囊癌组织中阳性表达率为 78 2 6 % ,胆囊癌组织与胆囊良性病变MMP 9表达水平之间有显著性差异 (P <0 0 0 1)。MMP 9表达与胆囊癌分化程度、临床分期、淋巴结转移、术后生存率有关。结论　MMP 9的表达可以作为判断胆囊癌淋巴结转移、评估预后的指标。     

AJCC第八版Ⅲ期不同亚组分型的胆囊癌临床特征及预后分析—基于SEER数据库的研究

目的 研究美国癌症联合委员会(AJCC)第8版Ⅲ期胆囊癌(GBC)亚组分型的临床特征、治疗方式及预后.方法 收集3?485名AJCC第8版Ⅲ期胆囊癌患者的临床资料、随访结果并进行对比.绘制并比较ⅢA和ⅢB,T3N0M0(ⅢA)、T1～2N1M0(ⅢB)和T3N1M0(ⅢB)的Kaplan-Meier生存曲线.单因素和C...     

A review of association of dietary factors in gallbladder cancer

Gallbladder cancer (GBC) is the prominent malignancy of hepato-biliary tract, being the fifth most common carcinoma for gastrointestinal tract in United States. Epidemiological studies world wide have implicated dietary factors in the development of gallbladder cancer. The ecological evidences indicate considerable geographic variation in the incidence of gallbladder cancer. However the variations in GBC incidence of different populations might be partly determined by their dietary variations. Higher intake of energy and carbohydrate possibly increase the risk of gallbladder cancer. Obesity plays an important role in the causation of GBC. Adequate intake of fruits and vegetables probably reduce the risk of GBC. This nutritional preventive effect against GBC could be attributed to high content of vitamins, carotenes and fibers. They can not be too emphatically stated as the sole determinants of GBC. It is apparently clear that a variety of essential nutrients can significantly modify the carcinogenic process. Furthermore, an attempt has been made to establish an association between dietary factors and the occurrence of gallbladder cancer.     

CA 125: a potential tumor marker for gallbladder cancer

BACKGROUND: CA 125 is a glycoprotein and a commonly used tumor marker in ovarian carcinoma. Its use in gallbladder carcinoma (GBC) has not yet been reported. We have henceforth examined for the first time the diagnostic utility of CA 125 in patients with gallbladder diseases. PATIENTS AND METHODS: Serum CA 125 was measured in 64 patients with GBC, 47 Gallstone disease (GSD) and 23 healthy volunteers by ELISA. CA 125 level was compared between different cohorts by non-parametric test (Kruskal Wallis and Mann-Whitney test). Receiver operating characteristic curve (ROC) was constructed to see the diagnostic utility of CA 125. Its level was also correlated with age, sex and clinico-pathological parameters of the patients included in the study. RESULTS: Mean value of CA 125 in patients with GBC, GSD and healthy volunteers was 77.44 +/- 141.31 U/ml, 7.85 +/- 5.40 U/ml, and 8.08 +/- 3.26 U/ml respectively and showed a statistically significant difference (P < 0.001). CA 125 at cut off value of 11 U/ml yielded 64% sensitivity and 90% specificity in differentiating benign from malignant gallbladder disease. CA 125 level increased with stage and grade of the GBC though this was not statistically significant. A higher level of CA 125 was found in presence of gallbladder mass, weight loss, ascites and loss of appetite compared to patients with GSD. No association of CA 125 was apparent with either age or sex of the patients. CONCLUSION: CA 125 has a diagnostic potential for GBC and can differentiate GBC from GSD in light of other clinical details.     

中晚期胆囊癌手术方式的临床分析

目的：探讨中晚期胆囊癌手术方式与预后关系。方法：回顾性分析1997年1月至2005年1月间收治的85例中晚期胆囊癌的临床资料，施行胆囊癌根治性切除术40例，扩大根治术25例，姑息性手术20例。结果：均获得病理诊断，腺癌51例（60％），最为常见。65例行根治术＋扩大根治术和85例总的术后的1年、3年、5年生存率分别为80．0％、61．5％、49．2％；67．1％、47．1％、37．6％。结论：胆囊癌根治术＋扩大根治术是提高中晚期胆囊癌切除率和疗效的有效方法。     

Primary carcinoma of gallbladder in Yazd, Iran: A 14-year study (1992–2006)

Aim: To investigate the clinico‐pathological profile and stage of disease at presentation of patients with carcinoma of the gallbladder diagnosed during 1992–2006 in Iran. Methods: During this study period 34 consecutive patients with gallbladder carcinoma were identified using a pathology‐based tumor database. The data extracted for each study patient included their gender, age at diagnosis, signs and symptoms, presence of gallstones and histopathological pattern of the gallbladder carcinoma and the UICC/AJCC TNM staging system was used for labeling the stages of the disease. Results: The median age of the 34 patients studied was 69.50 with most between 61 and 70 years of age. The age range of the men was between 53 and 80 years with a median age of 71.50 years and that of the women was between 33 and 79 years with a median age of 68.50 years. The most common symptom was pain in the right hypochondrium. More women had gallstones (15/34) than men (3/10). Adenocarcinoma was the most common histopathological type (91.18%) with the commonest subtype being papillary (47.06%). Eighteen patients had stage IB and stage IIA (52.94%) carcinomas whereas stages IIB and III were observed in six (17.6%) and seven cases (20.6%), respectively. Only three cases (8.82%) were seen in stage IV. The follow up of gall bladder carcinoma (GBC) patients in this study ranged from 6 to 60 months. However, there was a progressive reduction of patients attending follow‐up oncology clinic, particularly by those who had stages III and IV of the disease. Conclusion: Most patients (52.94%) presented with early disease (stage IB and IIA) which carries a good prognosis. Early detection of GBC and a national consensus for the evidence‐based management of GBC in Iran should be the major components of a strategy aimed at improving therapeutic outcome.     

三氧化二砷诱导人胆囊癌GBC细胞凋亡及其机制研究

背景与目的：胆囊癌由于缺乏特异性的临床表现，确诊时多属晚期，手术切除率较低；且常规化疗药物对胆囊癌的疗效较差，因此需寻找治疗胆囊癌新的有效药物。三氧化二砷在治疗急性早幼粒细胞白血病中取得了突破性成果，近年来它在实体瘤的研究中颇受关注。本研究旨在探讨As2O3对人胆囊癌GBC细胞系诱导凋亡的生物学效应及作用机制。方法：用Hoechest33258染色、流式细胞仪和DNA凝胶电泳研究As2O3诱导细胞凋亡情况。用Western blot分析As2O3对凋亡相关蛋白Bcl-2、Bcl—xL、Bid、Bak、Bax、cleaved—Caspase-3和cleaved—Caspase-9的表达影响。构建Bcl-2的表达质粒，并用Lipo2000转染GBC细胞，并检测As2O3诱导细胞凋亡情况。结果：As2O3可诱导GBC细胞凋亡。蛋白水平的检测表明As2O3可使细胞Bcl-2、Bcl—xL的表达下降，Bid、Bak和Bax表达升高，并促进Caspase-3和Caspase-9的剪切。过表达Bcl-2可抑制As2O3诱导的凋亡。结论：As2O3可诱导胆囊癌细胞的凋亡，并主要通过下调Bcl-2基因的表达来实现。     

Node positivity in T1b gallbladder cancer: A high volume centre experience

IntroductionIdentification of early stage gallbladder cancer (GBC) is difficult with simple cholecystectomy being considered curative for T1a GBC but T1b requires radical cholecystectomy due to chances of lymph node metastasis. However there is no consensus regarding the optimal treatment strategy for T1b disease.MethodologyA retrospective review of a prospectively maintained database of GBC patients operated at our institute from March 2010 to March 2021 was conducted. Only patients with proven gallbladder adenocarcinoma on final histopathology report were included.ResultsA total of 1245 patients of suspected GBC who underwent surgery during this period with 76 patients of T1b stage were analysed. We divided the group into a node positive cohort (n = 16, 9 received neoadjuvant treatment due to uptake in periportal nodes and 7 patients were pN1) and a node negative cohort (n = 60). The median nodal harvest was 8 nodes (2–24 nodes). Considering the radiological and pathological parameters, the rate of lymph node positivity was 21% (16/76). The overall major morbidity was 5.2% and there was no mortality. After a median follow up of 47.5 months, 3-year OS and DFS of the node negative and positive cohort was 96.7%, 91.7% and 75% and 62.5% (p = 0.058). The node positive cohort had 43% recurrences whereas the node negative cohort had 8.3% with all recurrences limited to periportal lymph nodes, distant nodes or liver metastasis.ConclusionNodal positivity for T1b gall bladder cancer ranges around 21% and radical surgery with complete peri –portal lymphadenectomy should be considered as standard of care.     

Genetic aberrations in gallbladder cancer

Gallbladder carcinoma (GBC) is the most common type of biliary tract carcinoma and the third commonest digestive tract malignancy in our region. Studies available in literature do not clearly define the molecular genetic mechanisms involved in the pathogenesis of GBC. Most of these studies are limited to protein expression analysis by immunohistochemistry and western blotting, and only a few have been done on mRNA (messenger RNA) and mutation analysis. This review aims to critically analyze all the available evidence on genetic aberrations in gallbladder carcinoma.