Advanced Gallbladder Carcinoma Research Articles

94P First-line chemotherapy plus immunotherapy versus chemotherapy alone for advanced gallbladder carcinoma

94P First-line chemotherapy plus immunotherapy versus chemotherapy alone for advanced gallbladder carcinoma

Metastatic lymph node ratio as an important prognostic factor in advanced gallbladder carcinoma with at least 6 lymph nodes retrieved

BackgroundThe metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined.MethodsFrom January 2007 to January 2018, 144 advanced GBC patients (T2–4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS).ResultsThe optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195–2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463–0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148–2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589–0.892) were independent prognostic factors for GBC (all P<0.05).ConclusionsLNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

Sister Mary Joseph nodule can be the only clinical sign of advanced gallbladder carcinoma

Sister Mary Joseph nodule can be the only clinical sign of advanced gallbladder carcinoma

HER2/ERBB2 overexpression in advanced gallbladder carcinoma: comprehensive evaluation by immunocytochemistry and fluorescence in situ hybridisation on fine-needle aspiration cytology samples

AimsAdvanced gallbladder carcinoma (AGBC) carries a poor prognosis with dismal survival. There are no data regarding HER2/ERBB2 expression in AGBC. This study evaluated the overexpression of HER2/ERBB2 in cytological aspirates...

Single-cell transcriptome analysis revealed the immune profile of PD-1 blockade in gallbladder carcinoma liver metastasis.

Gallbladder carcinoma is the most common cancer of the biliary tract, and the immune checkpoint blockade showed promising efficacy in the treatment of advanced gallbladder carcinoma. However, the underlying mechanisms remain unknown. Single-cell RNA sequencing was used to reveal immune cell dynamics in an anti-PD-1 responder with gallbladder carcinoma liver metastases. Gene set variation analysis, pseudotime analysis, single-cell regulatory network inference and clustering analysis, and CellChat analysis were used to identify the functions of each cell cluster. Immunohistochemistry and multicolored immunohistochemistry analysis were applied to confirm the intratumoral cell types, and the prognostic value of CXCL13+CD8+T cells in patients with gallbladder carcinoma liver metastases with immunotherapy was evaluated. Four biliary tract carcinoma and 3 immunotherapy bulk RNA-seq datasets were analyzed to investigate the prognostic value of CXCL13+CD8+T cells and SPP1+TAMs. A total of 19,648 high-quality single-cell transcriptome data were obtained from liver metastasis before and after aPD-1 therapy. We discovered improved cytotoxic activity in CD8+T cells and enhanced proinflammatory phenotypes in myeloid cells. The identified SPP1+TAMs were related to poor prognosis. The increased effector/memory T cells represented characteristics similar to exhausted T cells in transitory status after aPD-1therapy, which may play a crucial role in the antitumor immune response. We further revealed that CXCL13+T cells in a high subtype of biliary tract carcinoma were characterized as a 'hot tumor' profile with high immune scores, correlated to the immunostimulatory context with favorable survival, and can predict effective responses to immunotherapy. Our study provided an overview of immune cell dynamics in gallbladder carcinoma liver metastases after aPD-1 treatment and highlighted the importance of CXCL13+T cells in biliary tract carcinoma and effective responses to immunotherapy, which would advance the understanding and treatment of the disease.

Current status and progress in laparoscopic surgery for gallbladder carcinoma.

Gallbladder carcinoma (GBC) is the most common biliary tract malignancy associated with a concealed onset, high invasiveness and poor prognosis. Radical surgery remains the only curative treatment for GBC, and the optimal extent of surgery depends on the tumor stage. Radical resection can be achieved by simple cholecystectomy for Tis and T1a GBC. However, whether simple cholecystectomy or extended cholecystectomy, including regional lymph node dissection and hepatectomy, is the standard surgical extent for T1b GBC remains controversial. Extended cholecystectomy should be performed for T2 and some T3 GBC without distant metastasis. Secondary radical surgery is essential for incidental gall-bladder cancer diagnosed after cholecystectomy. For locally advanced GBC, hepatopancreatoduodenectomy may achieve R0 resection and improve long-term survival outcomes, but the extremely high risk of the surgery limits its implementation. Laparoscopic surgery has been widely used in the treatment of gastrointestinal malignancies. GBC was once regarded as a contraindication of laparoscopic surgery. However, with improvements in surgical instruments and skills, studies have shown that laparoscopic surgery will not result in a poorer prognosis for selected patients with GBC compared with open surgery. Moreover, laparoscopic surgery is associated with enhanced recovery after surgery since it is minimally invasive.

High predictive ability of apparent diffusion coefficient value for wall-invasion pattern of advanced gallbladder carcinoma.

The wall-invasion pattern classification of advanced gallbladder carcinoma (GBC) has been reported. However, its association with clinical findings remains unclear. We aimed to clarify relationships between clinicopathological characteristics, prognosis, and apparent diffusion coefficient (ADC) values of advanced GBC based on the wall-invasion pattern. We reviewed the data of 37 patients who had undergone advanced GBC cholecystectomy at our institution between 2009 and 2021. Clinicopathological findings, prognosis, and ADC values were retrospectively analyzed. Based on the wall-invasion pattern, patients were classified into infiltrative growth (IG) type (n = 22) and destructive growth (DG) type (n = 15). In the DG-type, the incidence of venous invasion (P = 0.027), neural invasion (P = 0.008), and lymph node metastasis (P = 0.047) was significantly higher than in the IG-type, and recurrent-free survival (RFS) was significantly shorter (P = 0.015); the median RFS was 11.4months (95% confidence interval, 6.3-16.5months) in the DG-type and not reached in the IG-type. The ADC value in the DG-type was significantly lower than in the IG-type (median, 1.19 × 10-3 mm2/s vs. 1.86 × 10-3 mm2/s, P < 0.001). The area under the receiver operating characteristic curve for the ADC values to differentiate wall-invasion patterns was 0.95 (95% confidence interval, 0.87-1.00). The optimal cutoff ADC value was 1.45 × 10-3 mm2/s (sensitivity, 92.9%; specificity, 90.9%). The wall-invasion pattern of advanced GBC is associated with its aggressiveness and prognosis, and can be predicted by ADC values with high accuracy.

18P Trastuzumab in HER2-amplified or overexpressed gallbladder cancer: Experience from an Indian cancer center

The prognosis of advanced gall bladder carcinoma (GBC) remains poor despite the addition of newer targeted therapies. HER2 is a potential therapeutic target expressed in up to 20% GBC. We present an analysis of advanced or metastatic HER2-amplified or overexpressed GBC treated with trastuzumab and chemotherapy from an Indian cancer center.

Giant Fibrous Polyp of the Gallbladder Showing a Periphery-Dominant Contrast Enhancement: How to Differentiate It From Early Carcinoma

Although polyp size and stalk diameter are significant for the differential diagnosis of a gallbladder polyp, it is necessary to catch genuine polyp characteristics to differentiate a giant fibrous polyp from gallbladder carcinoma (GBC). This case report analyses the images and their correlation with the pathology. Transabdominal sonography revealed gallstones and a giant pedunculated gallbladder polyp measuring 32 × 18 × 14 mm with a thick stalk. The polyp lacked a hyperechoic surface line and was not delineated by either a deep hypoechoic area or a conically thickened outermost hyperechoic layer. Contrast-enhanced ultrasonography (CEUS) depicted a periphery-dominant enhancement, during the post vascular phase. A noncontrast computed tomogram (CT) did not demonstrate a gallbladder mass; meanwhile, a dynamic study revealed an enhanced polyp showing a periphery-dominant enhancement. Hence, without diagnostic findings suggestive of an obvious advanced GBC or excluding an early GBC, a full-thickness laparoscopic cholecystectomy was performed. The histopathology demonstrated a fibrous polyp with a thick stalk. In conclusion, a giant gallbladder polyp with a thick stalk showing a periphery-dominant contrast enhancement could suggest a fibrous polyp.

Extended Cholecystectomy with Reconstruction of Right Hepatic Artery for Carcinoma Gallbladder: A Case Report

The role of vascular reconstruction in surgical resection of advanced carcinoma gall bladder remains unclear, with scarce available literature. Evaluating the benefit of curable resection against the risk of increased postoperative morbidity remains a fine balancing act. Here, we report a case of a 45-year-old male who presented with obstructive jaundice and significant weight loss over 3 months. CECT showed bilateral IHBRD with patent primary confluence and an enhancing polypoidal mass in the proximal CBD of size 11 x 12 mm, in continuity with asymmetric mural thickening of GB neck. Fat planes with vascular structures were seen to be preserved. Possibilities of carcinoma gall bladder or cholangiocarcinoma were considered. Patient underwent ERCP and stenting of the right ductal system for resolution of jaundice. Extended cholecystectomy with extrahepatic bile duct resection and Roux-En-Y hepaticojejunostomy was performed. Intraoperatively, right hepatic artery was found involved with tumor; therefore, a 1 cm segment of the artery was resected and end to end anastomosis was done. Finally, a diagnosis of adenocarcinoma of gallbladder with positive liver resection margin (R1 resection) was made on histopathological examination. The resected right hepatic artery margins, however, were found to be free of tumor. Post-operative course remained uneventful, with no vascular complications. Patient received adjuvant chemoradiotherapy. He remains symptom free at 10 months post-surgery. Our case highlights that right hepatic artery reconstruction can be done in advanced carcinoma gallbladder with low surgical risk and that it remains a viable option for achieving curative resection.

Associating Portal Vein Embolization with Extended Resection Doesn’t Improve Outcomes in Surgical Management of Locally Advanced Gall Bladder Carcinoma

Introduction: Portal vein embolization(PVE) is established as a safe and effective method to increase the size of the future liver remnant(FLR) in cholangiocarcinoma, hepatocellular carcinoma and colorectal cancer liver metastasis. Results in gallbladder carcinoma(CaGB) have not been assessed comprehensively. We evaluated the outcome of PVE in patients with locally advanced CaGB.

Plasma-derived candidate biomarkers for detection of gallbladder carcinoma

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

Concomitant endoscopic biliary, duodenal and colonic stent placement for advanced carcinoma of gall bladder

Concomitant endoscopic biliary, duodenal and colonic stent placement for advanced carcinoma of gall bladder

Neoadjuvant Chemotherapy for Advanced Gallbladder Cancer: Do We have Enough Evidence? A Systematic Review.

BackgroundRecently for advanced gallbladder carcinoma, neoadjuvant chemotherapy has emerged as an important strategy in place of adjuvant chemotherapy with the hope that it will help to improve the resectability and survival.Aim and objectiveThe goal was to conduct a systematic review of published publications on the benefits of neoadjuvant chemotherapy for advanced gallbladder cancer treatment.Materials and methodsThis systematic review followed the Meta-analysis Of Observational Studies in Epidemiology standards. The clinical benefit rate of neoadjuvant chemotherapy, curative resectability rate, and R0 resection were the major outcomes of interest. The secondary outcomes of interest were overall and disease-free survival.ResultsSix published papers were included (n = 420). One-hundred and twenty-eight cases (30.47%) despite receiving neoadjuvant chemotherapy had disease progression. Although 67.38% of patients (283 of 420) in this systematic review showed good response to the neoadjuvant chemotherapy, just 51.66% (217 of 420 cases) were operated, out of which only 171 cases were deemed to be feasible for surgical resection and had curative resection. Out of the cases that underwent curative surgery, 91.81% had R0 resection (157 out of 171 patients). The overall survival rate was found to be 18.5–50.1 months for patients in whom curative surgery was done and 5.0–10.8 months for nonsurgery patients.ConclusionNo sufficient data exist to advocate the regular use of neoadjuvant chemotherapy in advanced gallbladder carcinoma, as data showed that only 1/3 of patients benefited and had a R0 resection. Further research should be the randomized controlled trials to further quantify the benefit of neoadjuvant chemotherapy in advanced gallbladder carcinoma.How to cite this articleNaveed S, Qari H, Thau CM, et al. Neoadjuvant Chemotherapy for Advanced Gallbladder Cancer: Do We have Enough Evidence? A Systematic Review. Euroasian J Hepato-Gastroenterol 2021;11(2):87–94.

The State of Immunotherapy in Hepatobiliary Cancers.

Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.

Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation.

BackgroundLong non-coding RNAs (lncRNAs) have been reported to play critical roles in human tumours, including gallbladder carcinoma (GBC). However, their biological functions and molecular mechanisms in tumorigenesis and progression remain largely unknown.MethodsQuantitative polymerase chain reaction (qPCR) was used to verify the expression of lncRNA myosin light chain kinase antisense RNA 1 (MYLK-AS1) in 120 pairs of GBC tissues and paired adjacent non-tumour tissues, as well as in six different GBC cell lines (NOZ, EH-GB1, OCUG-1, GBC-SD, SGC-996 and QBC-939). Cell counting kit 8 was applied to explore cell proliferation and drug sensitivity assays. The target miRNAs (miR) of MYLK-AS1 and downstream target genes were predicted using Starbase 3.0 software and confirmed by double luciferase reporting test. The expression of proteins was assessed using Western blot assay.ResultsHere, we demonstrated that MYLK-AS1 was significantly upregulated and correlated with a poor prognosis and poor clinical characteristics in GBC. Furthermore, the forced expression of MYLK-AS1 significantly promoted GBC cell proliferation and resistance to gemcitabine in vitro. Mechanistically, MYLK-AS1 functioned as an efficient miR-217 sponge, thereby releasing the inhibition of enhancer of zeste 2 polycomb repressive complex 2 (EZH2) subunit expression. MYLK-AS1 promoted GBC cell proliferation and resistance to gemcitabine by upregulating EZH2 expression, and EZH2 was confirmed as a direct target of miR-217.DiscussionOur results confirmed that the chemoresistant driver MYLK-AS1 might be a promising candidate as a therapeutic target for the treatment of advanced GBC.

A case report of iodine-125 seed placement during operation for the treatment of advanced gallbladder carcinoma with septic shock*

Abstract This case report describes a patient with advanced gallbladder cancer who developed septic shock associated with iodine-125 (125I) seed implantation. The treatment process is described to provide a clinical reference for similar cases. A 52-year-old woman with recurrence of advanced gallbladder cancer underwent 125I seed implantation and developed postoperative sepsis with septic shock. The blood culture suggested infection with Aeromonas caviae and Enterococcus faecalis. Vancomycin and imipenem were immediately administered according to the drug sensitivity results, along with immunoglobulin therapy and vasoactive drugs. The patient’s condition gradually stabilized after comprehensive treatment. Sepsis with septic shock is a rare but potentially fatal complication of 125I seed implantation. Timely administration of broad-spectrum antibiotics, immunoglobulin therapy, and vasoactive drugs is very important to stabilize the patient’s condition. Our treatment of this patient can serve as a reference for clinicians to manage this complication in similar cases.

Outcome of radical surgery for gallbladder carcinoma according to TNM stage: implications for adjuvant therapeutic strategies.

Outcomes following surgery for advanced gallbladder carcinoma remain unsatisfactory. This study aimed to determine the surgical outcome and effectiveness of adjuvant chemotherapy according to TNM stage in patients with gallbladder carcinoma. A total of 200 patients undergoing surgery for gallbladder carcinoma were enrolled. Clinicopathological data were evaluated and surgical outcomes were compared between patients with and without adjuvant chemotherapy according to TNM stage. The 5-year overall survival (OS) after resection for patients with stage I (n= 27), IIA (n = 18), IIB (n = 28), IIIA (n = 25), IIIB (n = 43), IVA (n = 7), and IVB (n = 52) disease was 90.8%, 94.4%, 73.6%, 33.7%, 57.7%, 14.3%, and 11.8%, respectively (p < 0.001). R0 resection was performed in all patients with stage I or II disease, in 89.7% of those with stage III disease, and 69.5% of those with stage IV disease. For patients with stage III disease, adjuvant chemotherapy was associated with improved OS (5-year OS, 60.9% vs. 41.1%; p = 0.028) and was an independent prognostic factor (hazard ratio, 2.045; p = 0.039). For patients with stage IV disease, adjuvant chemotherapy appeared to affect OS (5-year OS, 25.1% vs. 5.3%; p = 0.041); R0 resection (hazard ratio, 1.882; p = 0.040) was the only independent prognostic factor. TNM stage clearly predicts survival after resection of gallbladder carcinoma. R0 resection with adjuvant chemotherapy is recommended for long-term survival in the multimodal management of patients with stage III or IV gallbladder carcinoma.

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

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

Meso-hepatectomy in a Locally Advanced Carcinoma Gallbladder in 21st Century: Is it Justified?

Introduction: Based on the 2017 systematic review and meta-analysis meso-hepatectomy appears to be safe and comparable in both peri-operative and long term outcomes while comparing patients undergoing extended hepatectomy. Majority included hepatocellular carcinomas(>95%), cholangiocarcinomas but none have carcinoma(ca) gallbladder(gb). Right extended hepatectomy after biliary drainage and portal vein embolisation is the treatment modality for advanced ca gb. It is common in low socioeconomic strata of India(South Asia). Majority(90%) of them don't achieve R0 resection due to disease progression and procedural complications. Chemotherapy can't be given unless bilirubin< 5. The main difference between cholangiocarcinoma and ca gb is that cholangiocarcinoma spreads along ducts but ca gb infiltrates locallly. Hence meso-hepatectomy is not an inferior oncologic surgery in advanced ca gb. Methods: 30 year old male presented with jaundice, weight loss. Scan showed gall bladder mass with hilar block and right hepatic artery(RHA) involvement. Maximum bilirubin was 24. He underwent biliary drainage and bilirubin came down to 14. Ultrasound doppler showed RHA block with good intra-hepatic flow. He underwent meso-hepatectomy with RHA excision and hepaticojejunostomy to right posterior sectoral duct and left duct. Blood loss was 1 litre with a duration of 10 hour. Post operatively neither there was liver failure nor bile leak. Histopathology report was T4N2Mx(ductal margins negative). He completed adjuvant chemotherapy and on follow up of 18 months found to have segment 6 metastasis and still on chemotherapy without jaundice. Conclusion: Meso-hepatectomy is a safer onco-surgical alternative to extended hepatectomy in selected cases of advanced gall bladder cancers.