Laparoscopic cholecystectomy based on Laennec approach via the cystic plate with lymphadenectomy in Calot's triangle for gallbladder neoplasms:Initial experience and technical details

Background:It is still challenging to define the exact stage of early gallbladder carcinoma with preoperative imaging.Generally,subserous gallbladder is dissected for the potential early gallbladder carcinoma,which may cause incomplete tumor resection or tumor spread especially for the patients with T2 stage.Here,we reported our experience and safety of Laennec approach via the cystic plate to dissect the whole gallbladder with lymphadenectomy in Calot's triangle for accurate diagnosis and stage in gallbladder neoplasms.Methods:The anatomical gap between Laennec capsule and the cystic plate serves as the landmark to dissect the whole gallbladder through Laennec approach.Laparoscopic cholecystectomy based on Laennec approach via the cystic plate,together with lymphadenectomy in Calot's triangle,was performed in 17 patients with gallbladder neoplasms.Results:All patients had less intraoperative bleeding,no gallbladder breakage,no bile leakage,and accurate intraoperative rapid pathological staging under the corresponding strategies.The duration of surgery was comparable to that of traditional laparoscopic cholecystectomy.Conclusion:Laparoscopic cholecystectomy based on Laennec approach via the cystic plate,together with lymphadenectomy in Calot's triangular is safe for gallbladder neoplasms.In the future,the prospective clinical trial is going on to confirm the feasibility and effectiveness of this approach.

Cholecystoenteric fistula in a patient with advanced gallbladder cancer: A case report and review of literature

BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue necrosis,perforation,and fistulogenesis.The most prevalent cause of CEF is chronic cholelithiasis,which rarely results from malignancy.Because the symptoms and laboratory findings associated with CEF are nonspecific,the condition is often misdiagnosed,pre-senting a challenge to the surgeon when detected intraoperatively.Therefore,a preoperative diagnosis of CEF is crucial.We present the case of a 57-year-old male with advanced gallbladder cancer(GBC)who arrived at the emergency room with persistent vomiting,abdominal pain,and diarrhea.An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second por-tion of the duodenum and transverse colon.We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula(CDF)or a cholecystocolonic fistula(CCF).He underwent multiple examinations,including esophagogastroduodenoscopy,an upper gastrointestinal series,colo-noscopy,and magnetic resonance cholangiopancreatography;the results of these tests con-firmed a diagnosis of synchronous CDF and CCF.The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon.His symptoms improved with supportive treatment while hospitalized.He initiated oral targeted therapy with lenvatinib for further anticancer treatment.CONCLUSION The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.

Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

Clinical relationship between MDR1 gene and gallbladder cancer

BACKGROUND: The most common mechanisms of mul- tidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene ex- pression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDR1 mRNA in primary gallbladder carcinoma, and analyze its clinical significance. METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 ca- ses of cholecystitis (archival paraffin-embedded tissues). RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05). The positive expression rate of P-gp and MDRlmRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin against Nevin , (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05). CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteris- tics , takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.

Fork head box M1 regulates vascular endothelial growth factor-A expression to promote the angiogenesis and tumor cell growth of gallbladder cancer

BACKGROUND Gallbladder cancer(GBC)is an aggressive type of biliary tract cancer that lacks effective therapeutic targets.Fork head box M1(FoxM1)is an emerging molecular target associated with tumor progression in GBC,and accumulating evidence suggests that vascular endothelial growth factor(VEGF)promotes various tumors by inducing neoangiogenesis.AIM To investigate the role of FoxM1 and the angiogenesis effects of VEGF-A in primary GBC.METHODS Using immunohistochemistry,we investigated FoxM1 and VEGF-A expression in GBC tissues,paracarcinoma tissues and cholecystitis tissues.Soft agar,cell invasion,migration and apoptosis assays were used to analyze the malignant phenotype influenced by FoxM1 in GBC.Kaplan-Meier survival analysis was performed to evaluate the impact of FoxM1 and VEGF-A expression in GBC patients.We investigated the relationship between FoxM1 and VEGF-A by regulating the level of FoxM1.Next,we performed MTT assays and Transwell invasion assays by knocking out or overexpressing VEGF-A to evaluate its function in GBC cells.The luciferase assay was used to reveal the relationship between FoxM1 and VEGF-A.BALB/c nude mice were used to establish the xenograft tumor model.RESULTS FoxM1 expression was higher in GBC tissues than in paracarcinoma tissues.Furthermore,the high expression of Foxm1 in GBC was significantly correlated with a malignant phenotype and worse overall survival.Meanwhile,high expression of FoxM1 influenced angiogenesis;high expression of FoxM1 combined with high expression of VEGF-A was related to poor prognosis.Attenuated FoxM1 significantly suppressed cell proliferation,transfer and invasion in vitro.Knockdown of FoxM1 in GBC cells reduced the expression of VEGF-A.Luciferase assay showed that FoxM1 was the transcription factor of VEGF-A,and knockdown VEGF-A in FoxM1 overexpressed cells could partly reverse the malignancy phenotype of GBC cells.In this study,we found that FoxM1 was involved in regulation of VEGF-A expression.CONCLUSION FoxM1 and VEGF-A overexpression were associated with the prognosis of GBC patients.FoxM1 regulated VEGF-A expression,which played an important role in the progression of GBC.

Preoperative lymphocyte to C-reactive protein ratio as a new prognostic indicator in patients with resectable gallbladder cancer

Background:Inflammation is often related to cancer,and several inflammatory scores have been established to predict the prognosis of various types of cancer.Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio(LCR)for predicting postoperative outcomes in patients with resectable gallbladder cancer(GBC).Methods:A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital,Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed.A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers.Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival.Results:Among the assessed variables,the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients(AUC:0.736).Decreased preoperative LCR was significantly associated with advanced tumor stage,including tumor invasion(P=0.018),lymph node metastasis(P=0.011)and TNM stage(P=0.022).A low preoperative LCR(cutoff threshold=145.5)was an independent risk factor for overall survival in patients with resectable GBC(P<0.001).Conclusions:The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.

Norcantharidin inhibits growth of human gallbladder carcinoma xenografted tumors in nude mice by inducing apoptosis and blocking the cell cycle in vivo

BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Box, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm(3), P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08+/-1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 and Bax proteins/mRNAs in the NCTD group compared with the control group. CONCLUSION: NCTD inhibits the growth of xenografted tumors of human gallbladder carcinoma in nude mice by inducing apoptosis and blocking the cell cycle in vivo.

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)

Influence of norcantharidin on proliferation,proliferation-related gene proteins prolifera-ting cell nuclear antigen and Ki-67 of human gallbladder carcinoma GBC-SD cells

BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and should be consi- dered for palliative treatment such as chemotherapy and ra- diotherapy. Unfortunately, reports of chemotherapy and radiotherapy for gallbladder carcinoma are disappointing. We investigated the influence of norcantharidin (NCTD) on proliferation, proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human gallbladder carci- noma were cultured by the cell culture technique. The ex- periment was divided into NCTD group and control group. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The streptavidin-biotin complex method was used to determine the expressions of prolifera- tion-related gene proteins PCNA and Ki-67 of human gall- bladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a dose- and time-dependent manner, with the IC50 value of 56.18 μg/ ml at 48 hours. After treatment with NCTD, the expression of PCNA (0.932 ±0.031 vs. 0.318 ±0.023, P<0.001) and Ki-67 (0.964 ±0.092 vs. 0.297 ±0.018, P<0.001) proteins were decreased significantly. CONCLUSION: NCTD inhibits the proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the expres- sion of their proliferation-related gene proteins PCNA and Ki-67.

Gallbladder sarcomatoid carcinoma:Seven case reports

BACKGROUND Gallbladder sarcomatoid carcinoma is a rare and aggressive tumor,and little is known about its clinical behavior,prognosis,and optimal treatment.CASE SUMMARY From 1997 to 2017,we collected seven cases of gallbladder sarcomatoid carcinoma at our institution.The median patient age was 68.5 years.Six(85.7%)patients were female.Overall,85.7%(6/7)of the tumors had a maximal diameter greater than 7 cm.Late TNM stage was associated with a significantly poor prognosis.All patients with advanced-stage(III/IV)disease died from metastases or disease progression shortly after surgery.One patient with stage IIIB disease who received adjuvant chemoradiotherapy(gemcitabine and capecitabine)achieved a progression-free survival(PFS)of 12 mo and overall survival of 15 mo,which might be the longest PFS reported among patients who ultimately experienced recurrence or metastasis.CONCLUSION Sarcomatoid carcinoma is a unique and aggressive gallbladder malignancy.Surgery is suggested as the first and only recognized treatment.There is a significant difference in prognosis between patients with early-stage and advanced-stage disease.Postoperative adjuvant therapy may bring survival benefits for locally advanced patients.Gemcitabine combined with fluorouracil and radiotherapy could be a potential strategy.

RESEARCH OF NUTRITIONAL AND IMMUNE STATUS IN PATIENTS WITH GALLBLADDER CARCINOMA RADICAL CHOLECYSTECTOMY

Objective To inquire the nutritional and immune status in patients with gallbladder carcinoma before and after radical cholecystectomy.Methods The nutritional and immune status in patients with gallbladder carcinoma were assessed in 1 week before surgery, and on 3rd day, 7th day, 14th day and 21st day after operation respectively.Results All of the nutritional parameters but the serum level of iron, TIBC and transfterrin recovered within 3 week after operation. Remarkable decrease of serum IgG, IgA, IgM and C 3, C 4 complement, IL 2, CD 4, CD 4/CD 8 ratio, and the remarkable increase of serum SIL 2R and CD 8( P <0.01) on 3rd day after operation.Conclusion Adequate iron should be supplemented after the radical cholecystectomy for gallbladder carcinoma in the third postoperative week. Radical cholecystectomy with complete resection of the tumor and removal of lymph nodes played the important roles in the recovery of immune function.

Fourier transform infrared spectroscopy of gallbladder carcinoma cell line

BACKGROUND: Fourier transform infrared (FT-IR) spectroscopy is a physical method applied to the study of cellular changes at the molecular level in various normal and diseased human tissues, including cancer. This study was undertaken to establish a cellular basis for the diagnosis of carcinoma tissue, using FT-IR spectroscopy to study a carcinoma cell line and investigating the specific spectral features of the cell line. METHODS: The FT-IR spectra of cultured gallbladder carcinoma cells (GBC-SD) smeared on a BaF(2) window were measured with a Nicolet Magna750-II FT-IR spectrometer. A comparative study was subsequently carried out between the spectra of cultured gallbladder carcinoma cells and those of corresponding carcinoma tissue. RESULTS: Several infrared spectral features were obtained, and the results suggest that the spectral features of the carcinoma cell line reflect those of carcinoma tissue, though the latter are more complex, probably due to the intrinsic complexity of the tissue. CONCLUSION: The diagnosis of carcinoma tissue by FTIR spectroscopy has a sufficient cellular basis.

AN IMMUNOHISTOCHEMICAL STUDY ON EXPRESSION OF CD44v6 PROTEIN IN HUMAN GALLBLADDER CARCINOMA

Objective To investigate the clinical significances of CD44v6 protein expression in human gallbladder carcinoma(GBC).Methods The immunohistochemical technique was used to detect the CD44v6 protein expression in 40 cases of GBC,12 cases of chronic cholecystitis,6 cases of adenoma and 4 cases of adenomyomatous hyperplasia.Results The positive rate of CD44v6 expression in gallbladder carcinoma and benign lesions was 72.5% and 0%,respectively( P <0.01),and it also correlated with the lymph node metastasis,pathologic differentiation and clinic staging,but there was no correlation among pathological types.Conclusion Detecting CD44v6 expression might be severed as an objective indicator for differential diagnosis,lymph node metastatic potency,tumor progress and prognosis in gallbladder carcinoma.

Associations between serum uric acid and hepatobiliary-pancreatic cancer:A cohort study

BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.

Textbook outcome in gallbladder carcinoma after curative-intent resection:a 10-year retrospective single-center study

Background:Textbook outcome(TO)can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement.We explored the factors associated with achieving a TO for gallbladder carcinoma(GBC)after curative-intent resection and analyzed the effect of adjuvant chemotherapy(ACT)on TO and non-TO patients.Methods:A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi’an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed.Multivariable logistic regression was used to investigate the factors associated with TO.Results:Among 540 patients with GBC who underwent curative-intent resection,223 patients(41.3%)achieved a TO.The incidence of TO ranged from 19.0%to 51.0%across the study period,with a slightly increasing trend over the study period.The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection(P=0.003).Age≤60 years(P=0.016),total bilirubin(TBIL)level≤34.1 mmol/L(P<0.001),well-differentiated tumor(P=0.008),no liver involvement(P<0.001),and T1-2 stage disease(P=0.006)were independently associated with achieving a TO for GBC after resection.Before and after propensity score matching(PSM),the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant;ACT improved the prognosis of patients in the non-TO group(P<0.05).Conclusion:Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection,and ACT can improve the prognosis of those with non-TO.

Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system

Hepatopancreatobiliary tumors are challenging to treat,and the advanced or metastatic forms have a very low 5-year survival rate.Several drug combinations have been tested,and new therapeutic approaches have been introduced in the last decades,including radiofrequency and heat based methods.Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant,tumoricidal,and chemoradiotherapy sensitizer effects.Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques.Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies.Hyperthermia in biliary cancers is a less investigated area.High local and overall responses to treatment,increased progression-free and overall survival,and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types.With the evolution of chemotherapeutic agents and the introduction of newer techniques,the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects.However,despite the many positive effects of hyperthermia,its use is still only known at the experimental level,and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.

Preoperative prediction of survival in resectable gallbladder cancer by a combined utilization of CA 19-9 and carcinoembryonic antigen

Background Currently,all frequently used staging systems in gallbladder cancer （GBC） are based on postoperative pathological examinations.In patients undergoing curative operation,there is no effective method to predict survival preoperatively.In this study,we explored whether a combined utilization of two tumor biomarkers,namely carbohydrate antigen 19-9 （CA 19-9） and carcinoembryonic antigen （CEA）,could give a preoperative prediction of survival in resectable GBC.Methods Seventy-three patients who underwent radical resection for GBC were included in this study.A retrospective analysis of clinical-pathological data was conducted.Results By multivariate analysis,CA 19-9 elevation （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 （group Ⅰ）,patients with elevation of CA 19-9 but without CEA （group Ⅱ）,and patients with nonelevations of either CA 19-9 or CEA （group Ⅲ）.The cumulative 5-year survival rates in groups Ⅰ,Ⅱ,and Ⅲ were 0,14.0％,and 42.8％,respectively （P ＜0.05）.Conclusions By a combined utilization of CA 19-9 and CEA,individualized prediction of survival is available in resectable GBC before operation.Extended radical operation brings the most prognostic benefits in patients with nonelevations of either CA 19-9 or CEA.However,if operation would be in a larger-scale destructive manner,careful consideration of surgical decisions should be made in patients with elevation of tumor biomarkers,especially CEA.

Expressions of farnesoid X receptor and myeloid cell leukemia sequence 1 protein are associated with poor prognosis in patients with gallbladder cancer

Background Farnesoid X receptor （FXR） regulates tumorigenesis, but its clinical significance in gallbladder cancer （GBC） remains unclear. This study investigated its clinical and prognostic significance in GBC patients, as well as its association with the anti-apoptotic protein, myeloid cell leukemia sequence 1 （MCL1） protein. Methods FXR and MCL1 expression in 42 primary GBC and 15 normal gallbladder tissues were analyzed by immunohistochemistry. The patients and samples were collected from Ren Ji Hospital from January 2005 to December 2010. Their association with clinicopathologic factors and prognosis, as well as the correlation between FXR and MCL1 protein expression were analyzed by statistical analyses. Results Compared with normal gallbladder tissues, FXR expression was decreased and MCL1 expression was increased in GBC, during progression of tumor node metastasis （TNM） stage. The Kaplan-Meier survival analysis showed that FXR low-expression and MCL1 over-expression were significantly associated with overall poor survival. Furthermore, multivariate analysis showed that FXR and MCL1 are both prognostic factors for GBC patients. FXR low-expression was significantly correlated with MCL1 over-expression. Conclusion FXR might be a new molecular marker to predict the prognosis of patients with GBC and a novel therapeutic target. Chin Med J 2014;127 （14）： 2637-2642

Vimentin significantly promoted gallbladder carcinoma metastasis

Background The precise molecular mechanisms underlying the gallbladder carcinoma （GBC） metastasis has not been fully elucidated. Methods In the present study, metastasis-associated proteins were identified by comparative proteomic analysis. The functional study of the candidate protein vimentin was further investigated. First, a pair of higher and lower metastatic sublines （termed GBC-SD/M3 and GBC-SD, respectively）, originated from the same parental cell line, was screened by spontaneous tumorigenicity and metastasis in vivo in animal study and further characterized by metastatic phenotypes analysis in vitro. Subsequently, a proteomic approach comprised two-dimensional gel electrophoresis analysis and mass spectroscopy was used to identify and compare the protein expression patterns between higher metastatic GBC-SD/M3 and lower metastatic GBC-SD cell lines. Then twenty-six proteins were identified. Results Among the 26 proteins identified, fourteen proteins were up-regulated and 12 proteins were down-regulated in GBC-SD/M3. Vimentin was identified and found to be overexpressed in GBC-SD/M3 as compared with GBC-SD. This result was further confirmed by quantitative PCR and Western blotting analysis. Furthermore, the cell migration and invasion potency of GBC-SD/M3 in vitro was remarkably suppressed after small interference RNA-mediated knockdown of vimentin. Moreover, immunoblot and immunohistochemical analysis on 12 human GBC specimens showed consistently increased vimentin expression in metastases compared with primary tumors. Conclusion Tumor vimentin level may reflect the pathological progression in some GBC and may be a useful marker for predicting tumor metastasis and a therapeutic target for the treatment of GBC patients with metastases.

Tumor biomarkers： help or mislead in the diagnosis of xanthogranulomatous cholecystitis？-analysis of serum CA 19-9,carcinoembryonic antigen, and CA 12-5

Background Xanthogranulomatous cholecystitis （XGC） is a rare type of gallbladder inflammation.Unlike other cholecystitis,it can be easily misdiagnosed as gallbladder cancer based on radiological images.In response to misdiagnosis,extended surgical treatments are inappropriately given to patients,which is not beneficial to their health and/or recovery.In this study,we set out to determine whether tumor biomarkers can help to avoid misdiagnosis in patients with XGC.Methods Between January 2005 and January 2012,a total of 37 preoperative patients at Sir Run Run Shaw Hospital were suspicious of having gallbladder cancer and was pathologically confirmed to be XGC after surgical operations.Before operations,all patients received a tumor biomarker test to verify diagnosis,which included serum CA 19-9,carcinoembryonic antigen （CEA）,and CA 12-5.Results A measured amount （54.05％） of cases （20 in 37） had at least one elevation over the thresholds of CA 19-9 （37 IU/L）,CEA （5 ng/ml）,and CA 12-5 （35 IU/L）,which increased the suspicion of malignancy and consequently enhanced the difficulty to make right diagnosis of XGC as benign.45.95％ of cases （17 in 37） had an elevation in CA 19-9.2.70％of cases （one in 37） had an elevation in CEA and 24.32％ of cases （nine in 37） had an elevation in CA 12-5.Analysis with Fisher＇s exact test discovered that the presence of common bile duct stone was a contributor to elevations of CA19-9 in patients with XGC.However,even in cases without common bile duct stones,42.86％ of patients （nine in 21） had elevations of at least one tumor biomarker.Among them,26.09％ of patients （six in 21） had elevations of CA 19-9,with the maximum of 536.29 IU/L.Conclusions The elevations of tumor biomarkers in XGC were frequent,suggesting their inabilities to clarify the disease＇s nature,especially when there was a suspicion of gallbladder cancer.Intraoperative frozen pathology of gallbladder might be a possible solution.However,it is against the en bloc surgical principle and has the potential to cause tumor cell spreading.More research should be conducted,such as the discovery of a novel biomarker,so that XGC can less likely be misdiagnosed as malignancy until the final pathological judgment.