Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer.

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Ponicidin inhibited gallbladder cancer proliferation and metastasis by decreasing MAGEB2 expression through FOXO4.

BACKGROUND: Gallbladder cancer (GBC) is the most aggressively malignant tumor in the bile duct system. The prognosis for patients with GBC is extremely poor. Ponicidin is a diterpenoid compound extracted and purified from the traditional Chinese herb Rabdosia rubescens, and showed promising anti-cancer effects in a variety of tumors. However, Ponicidin has not been investigated in GBC. METHODS: CCK-8, colony formation assay and EdU-488 DNA synthesis assay were performed to investigate the effect of Ponicidin on GBC cells proliferation. Cell invasion and migration assays and wound-healing assay were used to explore the effect of Ponicidin on invasion and migration ability of GBC cells. mRNA-seq was adopted to explore the underlying mechanisms. Western blot and immunohistochemical staining were conducted to detect the protein level. CHIP assay and dual-luciferase assay were used to validate binding motif. Nude mouse model of GBC was used to assess the anti-tumor effect and safety of Ponicidin. RESULTS: Ponicidin inhibited the proliferation and cell invasion and migration of GBC cells in vitro. Moreover, Ponicidin exerted anti-tumor effects by down-regulating the expression of MAGEB2. Mechanically, Ponicidin upregulated the FOXO4 expression and promoted it to accumulate in nucleus to inhibit the transcript of MAGEB2. Furthermore, Ponicidin suppressed tumor growth in the nude mouse model of GBC with excellent safety. CONCLUSION: Ponicidin may be a promising agent for the treatment of GBC effectively and safely.

Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway.

CONTEXT: Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. Isoalantolactone (IAL), an active sesquiterpene lactone compound isolated from the roots of Inula helenium L. (Asteraceae), has antitumour effects. OBJECTIVE: This study investigates the effects of IAL on GBC. MATERIALS AND METHODS: In vitro, NOZ and GBC-SD cells were treated with IAL (0, 10, 20 and 40 µM) for 24 h. The DMSO-treated cells were selected as a control. Cell proliferation, migration, invasion and apoptosis were measured by the CCK-8 assay, transwell assay, flow cytometry and western blot. In vivo, subcutaneous tumour xenografts were constructed by injecting nude mice (BALB/C) with 5 × 106 NOZ cells. Mice were divided into the control group (equal amount of DMSO), the IAL group (10 mg/kg/day) and the IAL + Ro 67-7476 group (IAL, 10 mg/kg/day; Ro 67-7476, 4 mg/kg/day). The study duration was 30 days. RESULTS: Compared with the DMSO group, cell proliferation of NOZ (IC50 15.98 µM) and GBC-SD (IC50 20.22 µM) was inhibited by about 70% in the IAL 40 µM group. Migration and invasion were suppressed by about 80%. Cell apoptosis rate was increased about three-fold. The phosphorylation level of ERK was decreased to 30-35%. Tumour volume and weight (about 80% reduction) were suppressed by IAL in vivo. Moreover, the effects of IAL were abolished by Ro 67-7476 in vitro and in vivo. DISCUSSION AND CONCLUSIONS: Our findings indicate that IAL could inhibit GBC progression in vitro and in vivo by inhibiting the ERK signalling pathway.

Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017-2019.

BACKGROUND: The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. METHODS: Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. RESULTS: There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50-65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100-100); 61% (95% CI: 45-83); 30% (95% CI: 21-43); and 9% (95% CI: 6-13) for stages I-IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39-64), compared to 29% (95% CI: 22-38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6-14) in patients who were palliated (N = 107) (p = <0.0001). CONCLUSION: The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III-IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required.

Feasibility for SERS-based discrimination of gallbladder cancer from polyp by indirect recognition of components in bile.

The aqueous solution extracted from raw bile juice is composed primarily of bile salts, with lower levels of bilirubin and its derivatives. Among them, the bilirubin and bilirubin-derived metabolites are the only surface-enhanced Raman scattering (SERS)-active components. An analytical scheme indirectly responsive and able to utilize all bile components, including SERS-inactive bile salts, was explored for SERS-based discrimination of gallbladder (GB) polyp and GB cancer. Initially, the surface of a SERS substrate (Au nanodendrite on Ni foil (AuND@NiF)) was covered with an alkanethiol molecule to generate a SERS signal and attract bile components by mutual interaction. For more effective recognition of bile components, 4 independent substrates covered with 4 different alkanethiols with various functional groups (SH(CH2)2CH3, SH(CH2)2NH2, SH(CH2)2COOH, and SH(CH2)2OH) were prepared. The SERS peaks of each substrate clearly varied on interaction with pure bile components as well as aqueous bile samples, and the SERS peaks in each substrate were individually characteristic. When the principal component (PC) scores of spectra obtained using the SH(CH2)2CH3- and SH(CH2)2OH-covered substrates were combined, the k-Nearest Neighbor-based discrimination accuracy was 100%, superior to those (90.6-96.9%) using individual substrates. The use of complementary bile component-induced spectral information provided by the two substrates was responsible for accurate discrimination. On the other hand, when bare AuND@NiF recognizing only SERS-active bilirubin derivatives was used, discrimination was unsatisfactory (accuracy: 75.0%).

Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy. METHODS: Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis. RESULTS: The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis. CONCLUSION: The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.

The efficacy and safety of 5-fluorouracil based adjuvant therapy in resected biliary tract cancer: A systematic review and meta-analysis.

OBJECTIVES: The adjuvant therapy (AT) for biliary tract cancer (BTC) patients after surgery has always been controversial. More therapeutic regimens and high-quality evidence were needed to evaluate AT's survival benefit further. Thus, this study was performed to investigate the efficacy and safety of the 5-fluorouracil (5-FU) regimen in resected BTC patients. METHODS: PubMed, Cochrane Library, Web of Science, and the Embase were systematically searched from inception to Feb.3, 2021, for eligible studies. The pooled analyses were performed using Review Manager, Stata, and SPSS software. RESULTS: A total of 9 trials involving 1339 participants were included in the meta-analysis. Resected BTC patients could significantly benefit from a 5-FU regimen (HR:0.51, 95%CI, 0.38-0.69, P<0.0001), regardless of gallbladder carcinoma (GBC) or cholangiocarcinoma (CCA). Moreover, both adjuvant chemotherapy (HR:0.61, 95%CI, 0.47-0.79, P=0.0003) and chemoradiotherapy (HR:0.35, 95%CI, 0.14-0.83, P=0.02) could significantly improve clinical survival of resected BTC patients than the surgery alone group. In the subgroup analyses, patients with node-positive (P=0.02) or vascular invasion disease (P=0.002) could better benefit from postoperative AT. CONCLUSION: This study provides the latest evidence to support the 5-FU regimen in resected BTC patients regardless of GBC or CCA. Furthermore, high-risk patients are more likely to benefit from it, such as node-positive or vascular invasion disease.

Recognition of potential therapeutic role of 2-hydroxy-3-methylanthraquinones in the treatment of gallbladder carcinoma: A proteomics analysis.

Gallbladder carcinoma (GBC), with early metastasis and high recurrence rates, is an enormous threat to health. As an anthraquinones monomer of traditional Chinese medicine Hedyotis diffusa, 2-hydroxy-3-methylanthraquinone (HMA) has been reported to inhibit the growth of several cancers. But in our preliminary study, HMA could only weakly induce GBC cell apoptosis. To explore other possible mechanism underlying the inhibition effect of HMA on GBC, this proteomics analysis was performed. A proteomics analysis was performed on one GBC cell line bought from the China Life Science Cell Bank. Several computational techniques were merged to develop analysis for those differently expressed proteins. A comparative protein-protein interaction network analysis was carried out among the differently expressed proteins to identify the proteins potentially inhibiting GBC. Thus, a GO and KEGG analysis was performed to identify the signaling pathways underlying a potential therapeutic role for HMA. A total of 285 proteins were affected by HMA, including 187 upregulated and 98 downregulated. The subcellular localization of differently expressed proteins were identified, including 142 in nuclear, 67 in cytoplasm, 67 in extracellular matrix, 46 in plasma membrane, 13 in mitochondrion, 3 in lysosome, and 1 in cytoskeleton. HMA could regulate EGFR, FN1, PLG, PLAUR, LAMA3, HRG, THBS1, PLAT, KNG1, ENAM, SERPINE1, ECM1, interleukin-8, and trypsin in GBC. Most of the regulated proteins involve in cell migration. Pathways including PI3K-Akt, Wnt, HIF-1, focal adhesion, microRNAs were regulated by HMA. HMA was shown to be an inhibition agent for GBC development, and this analysis would contribute to the development of new anti-GBC drugs.

Massive cerebral air embolism following percutaneous transhepatic biliary drainage: A case report.

RATIONALE: Cerebral air embolism from portal venous gas rarely occurs due to invasive procedures (e.g., endoscopic procedures, liver biopsy, or percutaneous transhepatic biliary drainage) that disrupt the gastrointestinal or hepatobiliary structures. Here, we report a rare case of fatal cerebral air embolism following a series of percutaneous transhepatic biliary drainage tube insertions. PATIENT CONCERNS: A 50-year-old woman with a history of cholecystectomy, liver wedge resection, and hepaticojejunostomy for gallbladder cancer presented with altered mental status 1 week after percutaneous transhepatic biliary drainage tube placement. DIAGNOSES: Extensive cerebral air embolism and acute cerebral infarction. INTERVENTIONS: Brain computed tomography and magnetic resonance imaging, hyperbaric oxygen therapy, medical therapy. OUTCOMES: Despite the use of hyperbaric oxygen therapy and medical treatment including vasopressors, the patient eventually died due to massive systemic air embolism. LESSONS: To date, there have been no reports of cerebral air embolism due to percutaneous transhepatic biliary drainage with pronounced radiologic images. We reviewed previously reported fatal cases associated with endoscopic hepatobiliary procedures and assessed the possible mechanisms and potential causes of air embolism.

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy Combined with Radical Surgery and Capecitabine on Stage III Gallbladder Cancer.

Purpose: The aim of the study was to investigate the effect of hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) combined with radical surgery and capecitabine on stage III gallbladder cancer. Method: Seventy-eight patients with stage III gallbladder cancer treated in our hospital between December 2015 and April 2019 were retrospectively enrolled. Depending on the treatment approach, the patients were divided into the control group (radical surgery and capecitabine) and the HIPEC group (hyperthermic intraperitoneal perfusion chemotherapy combined with radical surgery and capecitabine). The patients were followed up by outpatient or through telephone until April 1, 2020. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using the Kaplan-Meier method and parallel log-rank test. Results: There were 43 cases in the control group and 35 cases in the HIPEC group. There were no significant differences in operation time, lymph node metastasis, microvascular infiltration, and nerve invasion; there was no significant difference in postoperative complications between the two groups (P > 0.05). The average hospitalization time of the HIPEC group was 23.0 ± 6.9 days, which was longer than the 20.0 ± 5.8 days of the control group (P < 0.05). The body temperatures of HIPEC group patients at 0 h and 6 h after operation were higher than those of patients in the control group (P < 0.05); however, the body temperature of the two groups gradually became the same at 12-24 h after operation. There was no liver and kidney damage in the two groups after surgery. The platelets in the HIPEC group were less than those in the control group (P < 0.05). The median survival time of HIPEC was 19.2 months, which was longer than 15.3 months in the control group. The 1-year survival rates of the two groups were 91.43% vs. 76.71%, and the 2-year survival rates were 26.29% vs. 17.53%, respectively (P < 0.05). Conclusion: HIPEC combined with radical surgery and capecitabine for stage III gallbladder cancer can effectively prolong survival time without increasing surgery-related complications.

A review of anti-tumour effects of ginsenoside in gastrointestinal cancer.

OBJECTIVES: Gastrointestinal cancer, one of the major causes of cancer-related deaths in the world, refers to malignant conditions of the gastrointestinal (GI) tract and other organs. Although conventional therapy has been successful to some extent in cancer treatment, drug resistance and cancer recurrence still limit the therapeutic efficacy. There is increasing evidence indicating that ginsenoside, as a kind of high nutritional value and widely used traditional Chinese medicine, could contribute to the promotion of treatment in GI cancer, which deserves further investigation. KEY FINDINGS: Based on previous studies, the possible mechanisms mainly include regulation of autophagy, apoptosis, proliferation, migration and angiogenesis. However, no studies recently have conducted a more in-depth review of the anti-cancer effects of ginsenoside in GI cancer. SUMMARY: Therefore, this review will summarise and analyse the latest developments in the anti-tumour effects of ginsenosides in GI cancer, thus may promote further research of the anti-tumour efficacy of ginsenoside.

Undertreatment of Gallbladder Cancer: A Nationwide Analysis.

BACKGROUND: Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer. METHODS: Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004-2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan-Meier and Cox proportional hazard methods. RESULTS: The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p < 0.0001), private insurance (41.6% vs 27.1%; p < 0.0001), academic centers (50.4% vs 29.7%; p < 0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p = 0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p = 0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p < 0.0001), negative margins on final pathology (90.1% vs 72.6%; p < 0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p < 0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p < 0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p = 0.0004). CONCLUSIONS: Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.

Protocol for a gallbladder cancer registry study in China: the Chinese Research Group of Gallbladder Cancer (CRGGC) study.

INTRODUCTION: Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population. METHODS AND ANALYSIS: The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers. ETHICS AND DISSEMINATION: The protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019-085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04140552, Pre-results.

Risk factors for gallbladder cancer development in northern India: A gallstones-matched, case-control study.

Background & objectives: A high incidence of gallbladder cancer (GBC) is observed in northern India. This study was aimed to identify the factors involved in developing GBC in this region. Methods: A gallstones-matched, case-control study was conducted in northern India. Ninety nine patients with GBC and gallstones (33 men and 66 women, mean age of 51.4 yr) comprised the case group, while 99 patients with cholelithiasis (40 men and 59 women, mean age of 45.7 yr) comprised the control group. All participants were interviewed to complete 183 questionnaire items that included 105 food items. Potential risk factors were identified using a multivariate analysis adjusted for age and sex. Significant risk factors were identified using a stepwise logistic-regression analysis. Results: Age (≥50 yr), education (illiterate), socioeconomic status (≤below poverty line), bowel habits (≤once a day), hypertension history, hypotensive drug use, non-vegetarian diet, use of firewood for cooking, tap water drinking, hand pump water drinking and high consumption of coffee and sweets were identified as the potential risk factors. In women, factors included menarche (<13 yr), number of pregnancies (≥3 pregnancies) and parity (≥3 babies). Of these factors, age, education, bowel habits, tap water drinking and multiple pregnancy and/or multiparity were identified as significant risk factors, whereas a high consumption of coffee and sweets or hypotensive drug use and/or hypertension history were protective factors. Interpretation & conclusions: Poor bowel habits and drinking unsafe water appear to be the main risk factors for developing GBC. These are, however, modifiable factors which are capable of decreasing the risk of GBC in the north Indian population.

Primary Hepatoid Adenocarcinoma of Gallbladder With MB21D2/GALNT12/ARID2 Mutations: A Case Report.

Background: Primary hepatoid adenocarcinoma of the gallbladder is a relatively rare type of extrahepatic adenocarcinoma. The genetic changes involved in this type of adenocarcinoma were unexplained so far. We reported a rare case of primary hepatoid adenocarcinoma of gallbladder with Mab-21 domain containing 2 (MB21D2), polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12), and AT-rich interaction domain 2 (ARID2) mutations, which was confirmed after surgical resection pathologically. Case Summary: A 69-year-old female with distention of hypogastrium and constipation received enema treatment, but ineffectively. No abnormalities were found on relevant physical examination. Then, the CT and MRI demonstrated a 3.3-4-cm soft tissue mass shadow in the neck of the gallbladder. The primary lesions consisted of two components: high-grade intraepithelial neoplasia of glands and hepatoid glands microscopically after laparoscope cholecystectomy. Immunohistochemical staining showed the sameness and difference of the two areas. Furthermore, tumor mutational burden (TMB) shows that the MB21D2, GALNT12, and ARID2 genes were mutated. Conclusion: This is the first report of primary hepatoid adenocarcinoma of the gallbladder with MB21D2, GALNT12, and ARID2 mutations. This will provide a theoretical basis for genetic changes in rare tumors.

Oroxylin A Exerts Its Antitumor Effects in Human Gallbladder Cancer via Inhibition of the PTEN/PI3K/AKT Signaling Pathway.

Gallbladder carcinoma (GBC) is one of the most common carcinomas of the biliary tract and is associated with aggressive malignancy and poor prognosis. Current therapeutic strategies, including surgery, radiotherapy, and chemotherapy, are not sufficient for the treatment of GBC, and new therapeutic strategies are urgently needed. The antitumor effects of oroxylin A (OrA), a natural flavonoid extracted from the dried roots of medicinal plants such as Scutellariae species (Radix Scutellariae), have been widely reported in various cancers. In this study, we first evaluated the antitumor activity and the underlying mechanism of action of OrA on GBC cells in vitro. Our results revealed that OrA significantly attenuated the proliferation, migration, and invasion of GBC cells, simultaneously promoting their apoptosis. Suppression of the phosphate on and tension homology deleted chromosome ten (PTEN)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway was found to be the underlying mechanism involved in the antitumor activity of OrA. In addition, experiments using a tumor xenograft mouse model confirmed the antitumor effects of OrA in vivo. Taken together, our findings indicate that OrA could be a potential antitumor agent for the prospective treatment of GBC.

Outcomes of Gallbladder Polyps and Their Association With Gallbladder Cancer in a 20-Year Cohort.

Importance: Gallbladder polyps (GP) are found in more than 4% of adult abdominal ultrasonographs. Their growth pattern and association with gallbladder cancer (GBC) are poorly defined. Objective: To determine the growth pattern of GPs and their association with GBC. Design, Setting, and Participants: This cohort study included 622 227 adult members (ie, aged 18 years or older) of Kaiser Permanente Northern California, an integrated health care delivery system, enrolled between January 1, 1995, and December 31, 2014. The GBC cohort comprised a total of 365 adults with GBC and prior ultrasonography, and the GP cohort comprised 35 970 adults with GPs present on ultrasonography. Data analysis was performed from March 2016 to November 2019. Exposures: Gallbladder polyps (quantitative size, <6 mm, 6 to <10 mm, and ≥10 mm or qualitative size [ie, tiny, small, moderate, and large]). Main Outcomes and Measures: For the GBC cohort, proportion of patients with GBC with polyps identified on preceding ultrasonograph. For the GP cohort, rates of GBC among those with polyps according to size and rate of GP growth of at least 2 mm over time. Results: The GBC cohort comprised 365 individuals (267 [73.1%] women; 173 [47.4%] white patients; median [interquartile range] age, 71 [61-79] years). After excluding 14 patients who did not have evaluation of polyp size, the final GP cohort comprised 35 856 adults, with 18 645 (52.0%) women, a median (interquartile range) age 50 (40-60) years, and 15 573 (43.3%) white patients. Gallbladder polyps were found in 22 patients (6.0%) in the GBC cohort and in 35 870 of 622 227 adults (5.8%) who underwent abdominal ultrasonography. Of these, 19 (0.053%) were diagnosed with GBC, similar to those without GP (316 of 586 357 [0.054%]). The unadjusted GBC rate per 100 000 person-years was 11.3 (95% CI, 6.2-16.3) overall and increased with polyp size, from 1.3 (95% CI, 0-4.0) with initial size of less than 6 mm (n = 17 531) to 128.2 (95% CI, 39.4-217.0) with initial size of 10 mm or larger (n = 2055). In those observed for at least 1 year, the rate was 3.6 (95% CI, 0.7-6.5) per 100 000 person-years. In 6359 patients with evaluable follow-up, unadjusted cumulative probabilities of polyp growth of at least 2 mm at 10 years were 66.2% (95% CI, 62.3%-70.0%) in polyps initially less than 6 mm and 52.9% (95% CI, 47.1%-59.0%) in polyps initially 6 mm to less than 10 mm. Conclusions and Relevance: In this study, GBC rates were low and similar among patients with and without GPs. Growth of 2 mm or more appeared to be part of GP natural history. The results call into question the strategy of proactively following GP to detect GBC.