New trends in diagnosis and management of gallbladder carcinoma

Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.

A deep learning model based on contrast-enhanced computed tomography for differential diagnosis of gallbladder carcinoma

Background:Gallbladder carcinoma(GBC)is highly malignant,and its early diagnosis remains difficult.This study aimed to develop a deep learning model based on contrast-enhanced computed tomography(CT)images to assist radiologists in identifying GBC.Methods:We retrospectively enrolled 278 patients with gallbladder lesions(>10 mm)who underwent contrast-enhanced CT and cholecystectomy and divided them into the training(n=194)and validation(n=84)datasets.The deep learning model was developed based on ResNet50 network.Radiomics and clinical models were built based on support vector machine(SVM)method.We comprehensively compared the performance of deep learning,radiomics,clinical models,and three radiologists.Results:Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance,HHL firstorder kurtosis,and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC,and were selected for developing radiomics model.Multivariate regression analysis revealed that age≥65 years[odds ratios(OR)=4.4,95%confidence interval(CI):2.1-9.1,P<0.001],lesion size(OR=2.6,95%CI:1.6-4.1,P<0.001),and CA-19-9>37 U/mL(OR=4.0,95%CI:1.6-10.0,P=0.003)were significant clinical risk factors of GBC.The deep learning model achieved the area under the receiver operating characteristic curve(AUC)values of 0.864(95%CI:0.814-0.915)and 0.857(95%CI:0.773-0.942)in the training and validation datasets,which were comparable with radiomics,clinical models and three radiologists.The sensitivity of deep learning model was the highest both in the training[90%(95%CI:82%-96%)]and validation[85%(95%CI:68%-95%)]datasets.Conclusions:The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

Application of laparoscopic surgery in gallbladder carcinoma

Gallbladder carcinoma(GC)is a rare type of cancer of the digestive system,with an incidence that varies by region.Surgery plays a primary role in the comprehensive treatment of GC and is the only known cure.Compared with traditional open surgery,laparoscopic surgery has the advantages of convenient operation and magnified field of view.Laparoscopic surgery has been successful in many fields,including gastrointestinal medicine and gynecology.The gallbladder was one of the first organs to be treated by laparoscopic surgery,and laparoscopic cholecystectomy has become the gold standard surgical treatment for benign gallbladder diseases.However,the safety and feasibility of laparoscopic surgery for patients with GC remain controversial.Over the past several decades,research has focused on laparoscopic surgery for GC.The disadvantages of laparoscopic surgery include a high incidence of gallbladder perforation,possible port site metastasis,and potential tumor seeding.The advantages of laparoscopic surgery include less intraoperative blood loss,shorter postoperative hospital stay,and fewer complications.Nevertheless,studies have provided contrasting conclusions over time.In general,recent research has tended to support laparoscopic surgery.However,the application of laparoscopic surgery in GC is still in the exploratory stage.Here,we provide an overview of previous studies,with the aim of introducing the application of laparoscopy in GC.

Expression of angiostatin cDNA in human gallbladder carcinoma cell line GBC-SD and its effect on endothelial proliferation and growth

AIM： To explore the influence of angiostatin up-regulation on the biologic behavior of gallbladder carcinoma cells in vitro and in vitro, and the potential value of angiostatin gene therapy for gallbladder carcinoma. METHODS： A eukaryotic expression vector of pcDNA3.1（＋） containing murine angiostatin was constructed and identified by restriction endonuclease digestion and sequencing. The recombinant vector pcDNA3.1-angiostatin was transfected into human gallbladder carcinoma cell line GBC-SD with Upofectamine 2000, and paralleled with the vector and mock control. The resistant clone was screened by G418 filtration. Angiostatin transcription and protein expression were examined by RT-PCR, immunofluorescence and Western-blot. The supernatant was collected to treat endothelial cells. Cell proliferation and growth in vitro were observed under microscope. RESULTS： Murine angiostatin cDNA was successfully cloned into the eukaryotic expression vector pcDNA3.1 （＋）. AFter 14 d of transfection and selection with G418, macroscopic resistant cell cloning was formed in the experimental group transfected with pcDNA 3.1（＋）-angiostatin and vector control. But untreated cells died in the mock control. Angiostatin was detected by RT-PCR and protein expression was detected in the experimental group by immunofluorescence and Western-blot. Cell proliferation and growth in v/tro in the three groups were observed respectively under microscope. No significant difference was observed in the growth speed of GBC- SD cells between groups that were transfected with and without angiostatin. After treatment with supernatant, significant differences were observed in endothelial cell （ECV-304） growth in vitro. The cell proliferation and growth were inhibited. CONCLUSION： Angiostatin does not directly inhibit human gallbladder carcinoma cell proliferation and growth in vitro, but the secretion of angiostatin inhabits endothelial cell proliferation and growth.

Laparoscopic vs open radical resection in management of gallbladder carcinoma:A systematic review and meta-analysis

BACKGROUND Radical resection offers the only hope for the long-term survival of patients with gallbladder carcinoma(GBC)above the T1b stage.However,whether it should be performed under laparoscopy for GBC is still controversial.AIM To compare laparoscopic radical resection(LRR)with traditional open radical resection(ORR)in managing GBC.METHODS A comprehensive search of online databases,including Medline(PubMed),Cochrane Library,and Web of Science,was conducted to identify comparative studies involving LRR and ORR in GBCs till March 2023.A meta-analysis was subsequently performed.RESULTS A total of 18 retrospective studies were identified.In the long-term prognosis,the LRR group was comparable with the ORR group in terms of overall survival and tumor-free survival(TFS).LRR showed superiority in terms of TFS in the T2/tumor-node-metastasis(TNM)Ⅱstage subgroup vs the ORR group(P=0.04).In the short-term prognosis,the LRR group had superiority over the ORR group in the postoperative length of stay(POLS)(P<0.001).The sensitivity analysis showed that all pooled results were robust.CONCLUSION The meta-analysis results show that LRR is not inferior to ORR in all measured outcomes and is even superior in the TFS of patients with stage T2/TNMⅡdisease and POLS.Surgeons with sufficient laparoscopic experience can perform LRR as an alternative surgical strategy to ORR.

Gallbladder Carcinoma of the Thyroid Revealed by an Acute Festered Thyroiditis: A Literature Study about a Case

The cutaneous extension of gallbladder thyroid carcinoma is uncommon and is among the aggressive forms of the disease. We are reporting the case of a woman of 54 that shows acute festered thyroiditis worsened by a necrotic ulcer wound on the skin lasting 3 weeks amid a big neglected hetero-multinodular goitre, evolving since 20 years. The anatomopathological test showed a gallbladder thyroid carcinoma of the thyroid with severe inflammation. The treatment consisted of a complete thyroidectomy with recurrent bilateral dredging. There was a favourable evolution. Gallbladder carcinoma, in its aggressive aspect, may be linked to the occurrence of acute festered thyroiditis. Therefore, the prognosis of our patient was favourable.

Nrf2 and Her3 co-expression in cholangiocarcinoma:Possible biological pathways for potential therapeutic approach

To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.

Mechanism of apoptosis induced by Mcl-1 inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells

Objective:To investigate the mechanism of apoptosis induced by myeloid cell leukemia-1(Mcl-1)inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells.Methods:GBC-SD cells were treated with different concentrations of UMI-77.GBC-SD cell proliferation and apoptosis were detected by MTT assay and Annexin V/PI.The expressions of Mcl-1,Bcl-2,Bcl-xL,Bax,Bak,cleaved-caspase 9,cleaved-caspase 3 and cleaved-PARP proteins in GBC-SD cells treated with UMI-77 were detected by Western blotting.Results:The results of MTT showed that different concentrations of UMI-77 had different inhibitory effects on cell proliferation of GBC-SD cells in a dose-dependent and time-dependent manner.Annexin V/PI results showed that the apoptosis rate was increasing gradually with the increase of UMI-77 concentration in a dose-dependent manner.Western blotting results showed that the expression of anti-apoptotic protein Mcl-1 was significantly decreased(p<0.05),and the expressions of Bax and Bak proteins were significantly increased respectively(p<0.05),but there were no significant changes in the expressions of Bcl-2 and Bcl-xL proteins,and the expression levels of cleaved-caspase 9,cleaved-caspase 3 and cleaved-PARP proteins were significantly increased(p<0.05)in 24 h after GBC-SD cells were treated with 10μmol/L of UMI-77.Conclusions:Mcl-1 inhibitor UMI-77 can induce the apoptosis of GBC-SD cells in a dose-dependent manner through the caspase-mediated endogenous apoptosis pathway.Therefore,Mcl-1 may become a new therapeutic target in the research on gallbladder cancer.

Gallbladder carcinoma: prognostic factors and therapeutic options

The outcome of gallbladder carcinoma is poor,and the overall 5-year survival rate is less than 5%. In early-stage disease,a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma,which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection,primary sclerosing cholangitis,an anomalous junction of the pancreaticobiliary duct,and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However,despite theoretical risk factors,only a third of gallbladder carcinomas are recognized preoperatively. In most patients,the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma''(IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore,the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However,the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry(GR),which records the largest number of incidental gallbladder carcinomas in Europe,indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature,a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1 b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately,there are diverse interpretations and practices regarding stageadjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.

Infiltrative xanthogranulomatous cholecystitis mimicking aggressive gallbladder carcinoma: A diagnostic and therapeutic dilemma

Xanthogranulomatous cholecystitis(XGC) is an uncommon variant of chronic cholecystitis. The perioperative findings in aggressive cases may be indistinguishable from those of gallbladder or biliary tract carcinomas. Three patients presented mass lesions that infiltrated the hepatic hilum,provoked biliary dilatation and jaundice,and were indicative of malignancy. Surgical excision was performed following oncological principles and included extirpation of the gallbladder,extrahepatic bile duct,and hilar lymph nodes,as well as partial hepatectomy. Postoperative morbidity was minimal. Surgical pathology demonstrated XGC and absence of malignancy in all three cases. All three patients are alive and well after years of follow-up. XGC may have such an aggressive presentation that carcinoma may only be ruled out on surgical pathology. In such cases,the best option may be radical resection following oncological principles performed by expert surgeons,in order that postoperative complications may be minimized if not avoided altogether.

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

AIM:To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio(PLR) in patients with gallbladder carcinoma(GBC).METHODS:Clinical data of 316 surgical GBC patients were analyzed retrospectively,and preoperative serum platelet and lymphocyte counts were used to calculate the PLR.The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic(ROC) curve.The primary outcome was overall survival,which was estimated by the Kaplan-Meier method.The log-rank test was used to compare the differences in survival.Then,we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients.RESULTS:For the PLR,the area under the ROC curve was 0.620(95%CI:0.542-0.698,P = 0.040) in detecting death.The cut-off value for the PLR was determined to be 117.7,with 73.6% sensitivity and 53.2% specificity.The PLR was found to be significantlypositively correlated with CA125 serum level,tumornode-metastasis(TNM) stage,and tumor differentiation.Univariate analysis identified carcinoembryonic antigen(CEA),CA125 and CA199 levels,PLR,TNM stage,and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data.Multivariate analysis showed that CA125 > 35 U/mL,CA199 > 39 U/mL,PLR ≥ 117.7,and TNM stage Ⅳ were independently associated with poor survival in GBC.When expressed as a continuous variable,the PLR was still an independent predictor for survival,with a hazard ratio of 1.018(95%CI:1.001-1.037 per 10-unit increase,P = 0.043).CONCLUSION:The PLR could be used as a simple,inexpensive,and valuable tool for predicting the prognosis of GBC patients.

Role of bacteria in carcinogenesis, with special reference to carcinoma of the gallbladder

Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic infl ammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is verypoor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specif ic molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.

Prognostic implications of estrogen receptor 1 and vascular endothelial growth factor A expression in primary gallbladder carcinoma

AIM: To investigate the prognostic significance of estrogen receptor 1(ER1) and vascular endothelial growth factor A(VEGF-A) expression in primary gallbladder carcinoma(GBC) to identify new prognostic markers for this malignancy.METHODS: Using immunohistochemistry, we investigated ER1 and VEGF-A expression in 78 GBC and 78 cholelithiasis(CS) tissues. The results were correlated with clinicopathological features. Univariate and multivariate analyses were performed to evaluate the relationship between ER1 and VEGF-A expression and patients' prognosis. Further Kaplan-Meier survival analysis was also performed. RESULTS: ER1 and VEGF-A expression was significantly higher in GBC compared with CS(47/78 vs 28/78, P < 0.05; 51/78 vs 33/78, P < 0.05). ER1 expression was correlated with gender(P < 0.05) and VEGF-A expression was correlated with tumor differentiation in GBC patients(P < 0.05). In univariate analysis, age and tumor node metastasis(TNM) stage were factors associated with GBC prognosis(P < 0.05). Although there was no statistical difference between the expression of ER1 or VEGF-A and overall survival, the high expression of ER1 combined with VEGF-A predicted a poor prognosis for GBC patients(16.30 ± 1.87 vs 24.97 ± 2.09, log-rank P < 0.05). In multivariate analysis, combined expression of ER1 and VEGF-A and TNM stage were independent prognostic factors for GBC patients(P < 0.05).CONCLUSION: Combined expression of ER1 and VEGF-A is a potential prognostic marker for GBC patients. Clinical detection of ER1 and VEGF-A in surgically resected GBC tissues would provide animportant reference for decision-making of postoperative treatment programs.

Surgical therapy and prognosis of sarcomatoid carcinoma of the gallbladder

BACKGROUND: Sarcomatoid carcinoma of the gallbladder is rare and its characteristics are poorly understood. This study aimed to understand the behavior and prognosis of sarcomatoid carcinoma of the gallbladder as well as its clinical manifestations and survival rate of patients after radical or palliative surgery, and to review the reported data worldwide and our 10 patients. METHODS: From 2004 to 2009, ten patients were pathologically diagnosed with sarcomatoid carcinoma of the gallbladder and underwent operation at our center. These characteristics, clinical presentations, tumor-node-metastasis (TNM) staging, surgical modes, and prognosis were reviewed, retrospectively. We collected the data of 46 patients reported in the English-language literature worldwide and analyzed the survival with ours. The survival rate was estimated using the Kaplan-Meier method, and was compared using the log-rank test. RESULTS: The median age of the 10 patients was 67 years (inter-quartile range 59-74 years), and the size of tumor inter-quartile ranged from 3.1 to 7.9 cm. In this series, 9 patients received radical surgery, and one undewent palliative surgery. There was no surgical mortality, and one patient underwent a second operation because of liver metastasis. The median survival time of the patients was 9 months (inter-quartile range 6-12 months), with 3 patients still being alive until follow-up; however, two patients had tumor recurrence. The data from the 56 patients (10 patients in our series and 46 reported elsewhere) statistically indicated that the median age was 66 years (inter-quartile range 61-74.5 years) and the overall median survival was 5.5 months (inter-quartile range 2.5-10 months). The survival time in the patients undergoing radical surgery (n=42) was significantly longer than that in the patients undergoing palliative surgery (n=14) (P=0.031). CONCLUSIONS: The survival of the patients with sarcomatoid carcinoma of the gallbladder is poor. Some patients may die shortly after the surgery because of recurrence or metastasis. However, radical surgery is still necessary if possible. (Hepatobiliary Pancreat Dis Int 2010; 9: 175-179)

Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma

BACKGROUND The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma(GBC)after curative resection remain unclear.AIM To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy.METHODS Patients with curatively resected advanced gallbladder adenocarcinoma(T3 and T4)were selected from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.A survival prediction model based on Bayesian network(BN)was constructed using the tree-augmented na?ve Bayes algorithm,and composite importance measures were applied to rank the influence of factors on survival.The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3.The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy.RESULTS A total of 818 patients met the inclusion criteria.The median survival time was 9.0 mo.The accuracy of BN model was 69.67%,and the area under the curve value for the testing dataset was 77.72%.Adjuvant radiation,adjuvant chemotherapy(CTx),T stage,scope of regional lymph node surgery,and radiation sequence were ranked as the top five prognostic factors.A survival prediction table was established based on T stage,N stage,adjuvant radiotherapy(XRT),and CTx.The distribution of the survival time(>9.0 mo)was affected by different treatments with the order of adjuvant chemoradiotherapy(cXRT)>adjuvant radiation>adjuvant chemotherapy>surgery alone.For patients with node-positive disease,the larger benefit predicted by the model is adjuvant chemoradiotherapy.The survival analysis showed that there was a significant difference among the different adjuvant therapy groups(log rank,surgery alone vs CTx,P<0.001;surgery alone vs XRT,P=0.014;surgery alone vs cXRT,P<0.001).CONCLUSION The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients.Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.

Impact of the number of examined lymph nodes on outcomes in patients with lymph node-negative gallbladder carcinoma

AIM To determine whether the number of examined lymph nodes(LNs) is correlated with the overall survival of gallbladder carcinoma(GBC) patients. METHODS Patients were collected from the Surveillance Epidemiology and End Results database(2004-2013) and categorized by the number of LNs into six groups: 1 LN, 2 LNs, 3 LNs, 4 LNs, 5 LNs, and ≥ 6 LNs. Survival curves for overall survival were plotted with a KaplanMeier analysis. The log-rank test was used for univariate comparisons.RESULTS In a cohort of 893 patients, the median number of examined LNs was two for the entire cohort. The survival for the 1 LN group was significantly poorer than those of the stage Ⅰ and Ⅱ disease groups and for the entire cohort. By dichotomizing the number of LNs from 1 to 6, we found that the minimum number of LNs that should be examined was four for stage Ⅰ, four or five for stage Ⅱ, and six for stage ⅢA disease. Therefore, for the entire cohort, the number of examined LNs should be at least six, which is exactly consistent with the American Joint Committee on Cancer criteria.CONCLUSION The examination of higher numbers of LNs is associated with improved survival after resection surgery for N0 GBC. The guidelines for GBC surgery, which recommend that six LNs be examined at least, are statistically valid and should be applied in clinical practice widely.

Rational therapeutic strategy for T2 gallbladder carcinoma based on tumor spread

AIM:To evaluate the adequacy of surgical treatment of T2 gallbladder carcinoma(GBCa)according to tumor spread in the subserosal layer. METHODS:A series of 84 patients with GBCa were treated at Saga University Hospital,Japan between April 1989 and October 2008.The tumor stage was graded according to the TNM staging for GBCa from the American Joint Committee on Cancer Manual 6th edition. Tumor staging revealed 30 patients with T2 tumors.T2 GBCa was divided into three groups histologically by the extent of tumor spread in the subserosal layer,using a score of ss minimum(ss min),ss medium(ss med)or ss massive(ss mas). RESULTS:For ss min GBCa,there was no positive pathological factor and patient survival was satisfactory with simple cholecystectomy,with or without extra-he- patic bile duct resection.For ss med GBCa,some pathological factors,h-inf(hepatic infiltration),ly(lymphatic invasion)and n(lymph node metastasis),were positive. For ss mas GBCa,there was a high incidence of positive pathological factors.The patient group with extra-hepatic bile duct resection with D2 lymph node dissection (BDR with D2)and those with S4a5 hepatectomy had significantly better survival rates.CONCLUSION:We suggest that radical surgery is not necessary for ss min GBCa,and partial hepatectomy and BDR are necessary for both ss med and ss mas GBCa.

Carcinoma in situ in a 7 mm gallbladder polyp: Time to change current practice?

Detection of polypoid lesions of the gallbladder is increasing in conjunction with better imaging modalities. Accepted management of these lesions depends on their size and symptomatology. Polyps that are symptomatic and/or greater than 10 mm are generally removed, while smaller, asymptomatic polyps simply monitored. Here, a case of carcinoma-in-situ is presented in a 7 mm gallbladder polyp. A 25-year-old woman, who had undergone a routine cholecystectomy, was found to have an incidental 7 mm polyp containing carcinoma in situ. She had few to no risk factors to alert to her condition. There are few reported cases of cancer transformation in gallbladder polyps smaller than 10 mm reported in the literature. The overwhelming consensus, barring significant risk factors for cancer being present, is that such lesions should be monitored until they become symptomatic or develop signs suspicious for malignancy. In our patient's case this could have led to the possibility of missing a neoplastic lesion, which could then have gone on to develop invasive cancer. As gallbladder carcinoma is an aggressive cancer, this may have led to a tragic outcome.

Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinoma

AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-fi ve patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m2) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m2) on day 1, and 2-3 h infusion of huachansu (20 mL/m2) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the fi rst, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response couldbe evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Non-hematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.

Comparative study of ROR2 and WNT5a expression in squamous/adenosquamous carcinoma and adenocarcinoma of the gallbladder

AIM To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS Poorly differentiated AC among AC patients aged >45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter >3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter = 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter >3 cm, TNM stage., lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass >= 3 cm, TNM stage. or., lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis.