Early host immune responses in a human organoid-derived gallbladder monolayer to Salmonella Typhi strains from patients with acute and chronic infections: a comparative analysis.

Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly. Interestingly, if not antibiotic-treated, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma. Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients would differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer model, and S. Typhi strains derived from acutely and chronically infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate host mitogen-activated protein kinase (MAPK) and S6 transcription factors. These variations might be attributed to differential cytokine signaling, predominantly via TNF-α and IL-6 production and appear to be influenced by the duration the isolate was subjected to selective pressures in the gallbladder. These findings represent a significant leap in understanding the complexities behind chronic S. Typhi infections in the gallbladder and may uncover potential intervention targets.

Cytomorphology of metastatic dedifferentiated/undifferentiated melanoma to the gallbladder: A case report and review of literature.

Dedifferentiated/undifferentiated melanoma (DM/UM) is a distinct subtype of malignant melanoma that tends to lose all melanocytic markers of differentiation. DM/UM pose major diagnostic challenges as they could be easily confused with UM sarcoma or carcinoma, thus necessitating the use of molecular studies such as Next Generation Sequencing (NGS) for detecting melanoma-compatible mutations to confirm such diagnosis. The capability of performing NGS molecular studies on small biopsy material with confirmation of adequacy via rapid on-site evaluation (ROSE) has tremendous value in diagnosing DM/UM. Herein, we present the first reported case of metastatic DM/UM to the gall bladder arising in a 60-year-old female with a prior history of right knee melanoma. We also shed light on the cytomorphology of DM/UM, review the literature on such a challenging entity, and emphasize the crucial role of molecular testing in their diagnosis.

Gallbladder's Adenocarcinoma With Enteroblastic Differentiation Revealed by 18 F-FDG PET/CT.

ABSTRACT: Gallbladder's adenocarcinoma with enteroblastic differentiation (GAED) is extremely rare. A 43-year-old woman complained of pain in the right upper abdomen, and enhanced CT showed a cystic and solid mixed mass in the hepatic hilar region. Adenocarcinoma with enteroblastic differentiation was pathologically identified. 18 F-FDG PET/CT revealed a lesion in the gallbladder neck with increased FDG uptake, accompanied by a cystic and solid mixed mass in the hepatic hilar region with liver and lymph node metastases. Gallbladder biopsy was also carried out, and GAED was confirmed. 18 F-FDG PET/CT may assist in the evaluation of GAED and guide biopsy.

Adenomyomas of the Gallbladder: An Analysis of Frequency, Clinicopathologic Associations, and Relationship to Carcinoma of a Malformative Lesion.

CONTEXT.­: The nature and associations of gallbladder (GB) "adenomyoma" (AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs. OBJECTIVE.­: To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM. DESIGN.­: Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM. RESULTS.­: Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio = 1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat-type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma arose from AM (invasion was confined to AM, and dysplasia was predominantly in AM). CONCLUSIONS.­: AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component (ie, the name "adeno-myoma" is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flat-type high-grade dysplasia or carcinoma in situ, and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.

Diagnostic performance and safety of endoscopic ultrasound-guided fine-needle aspiration/biopsy for gallbladder lesions.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy (EUS-FNA/FNB) is not fully established as a pathological sampling tool for gallbladder lesions due to limited evidence. We therefore aimed to clarify the effectiveness and safety of this procedure in a large-population cohort. METHODS: This study retrospectively evaluated the diagnostic yield of EUS-FNA/FNB for accurately differentiating between benign and malignant gallbladder lesions. Puncture targets included the gallbladder mass, lymph node, and liver mass. Adverse events and factors associated with diagnostic accuracy were analyzed as well. RESULTS: In 187 patients with gallbladder lesions undergoing EUS-FNA/FNB, 18 benign lesions and 169 malignant lesions were identified. Overall sampling adequacy was 98% (184/187). The diagnostic accuracy of EUS-FNA/FNB was 97% (182/187), sensitivity was 97% (164/169), and specificity was 100% (18/18). A single postprocedural complication (minor bleeding) was recorded in one patient. In the 169 cases of malignancy, 203 sites were punctured for pathological sampling of the primary mass (n = 94), lymph node (n = 79), and metastatic liver mass (n = 30). No significant difference was found for diagnostic accuracy among the puncture sites (P = 0.70). In cases having specimens obtained from the primary mass, the accuracy of those targeting liver invasion sites was significantly higher than that of other sites (98% vs. 83%, P < 0.01). CONCLUSION: EUS-FNA/FNB demonstrated clinical usefulness and safety for the pathological diagnosis of gallbladder lesions, with high diagnostic yield and a low incidence of adverse events. Targeting the site of liver infiltration may improve the diagnostic rate of EUS-FNA/FNB in the primary mass.

Risk stratification model for incidentally detected gallbladder polyps: A multicentre study.

PURPOSE: We aimed to develop a 4-level risk stratification model using a scoring system based on conventional ultrasound to improve the diagnosis of gallbladder polyp. METHOD: Patients with histopathologically confirmed gallbladder polyps were consecutively recruited from three medical centres. Conventional ultrasound findings and clinical characteristics were acquired prior to cholecystectomy. Risk factors for neoplastic and malignant polyps were used to build a risk stratification system via interobserver agreement and multivariate logistic regression analysis. The model was retrospectively trained using 264 pre-surgical samples and prospectively validated using 106 pre-surgical samples. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and malignant polyp rate. RESULTS: In total, 370 patients (mean age, 51.68 ± 14.41 years, 156 men) were enrolled in this study. Size (≥12 mm), shape (oblate or round), single, vascularity, gallbladder stone or sludge were considered risk factors for neoplastic polyps. Size (≥14 mm), shape (oblate), single, disrupted gallbladder wall, and gallbladder stone or sludge were risk factors for malignant polyps (all p < 0.05). In the scoring system, the sensitivity, specificity, and AUC of score ≥ 9 in diagnosing neoplastic polyps were 0.766, 0.788, and 0.876 respectively; and the sensitivity, specificity, and AUC of score ≥ 15 in diagnosing malignant polyps were 0.844, 0.926, and 0.949 respectively. In our model, the malignancy rates at the four levels were 0 % (0/24), 1.28 % (2/156), 9.26 % (5/54), and 70.37 % (38/54), respectively. CONCLUSIONS: The 4-level risk stratification model based on conventional ultrasound imaging showed excellent performance in classifying gallbladder polyps.

Decoding the Conundrum: Navigating Intra-operatively Encountered Suspicious Gallbladder Wall Thickening with Laparoscopic Transhepatic Needle Decompression and Beyond Cystic Plate Cholecystectomy.

BACKGROUND: Suspicious gallbladder wall thickening encountered during laparoscopic cholecystectomy poses challenges in its management. This study aims to address this problem by proposing a technique that involves laparoscopic transhepatic needle decompression and modified cystic plate cholecystectomy. METHODS: In this report, we describe the case of a 36-year-old female with symptomatic gallstone disease and ultrasound findings of a well-distended gallbladder with a uniform wall thickness. Diagnostic laparoscopy revealed a distended, tense gallbladder with suspicious areas of thickness. Transhepatic aspiration was performed for gallbladder decompression, followed by modified cystic plate cholecystectomy with preservation of the thin rim of liver tissue over the cystic plate. The gallbladder was removed in a specimen bag, and final histopathology showed a hyalinized gallbladder wall with calcification and pyloric gland metaplasia, with liver tissue adhered to the gallbladder wall (Video). RESULTS: The proposed technique aimed to minimize the risk of bile spillage and violation of oncological planes while maintaining surgical integrity. It offers a middle path between standard and extended cholecystectomy, reducing the chance of over- or under-treatment. This approach ensures patient safety, minimizes the need for conversion to open surgery, and preserves the tumour-tissue interface. CONCLUSION: Intraoperatively encountered suspicious gallbladder wall thickening can be effectively managed with laparoscopic transhepatic needle decompression and modified cystic plate cholecystectomy.

Intraoperative hypertensive crisis in a dog with functional paraganglioma of the gall bladder.

A 15-year-old spayed female mongrel presented with anorexia and an abdominal mass. The mass originated from the gall bladder and was surgically resected along with divisionectomy of the central hepatic division. Paroxysmal hypertension and tachycardia were noted during manipulation of the mass. Following resection, arterial blood pressure decreased significantly. Histopathological analysis confirmed a diagnosis of neuroendocrine neoplasm. Immunohistochemical staining for synaptophysin and chromogranin A yielded diffuse and strong positive results, while gastrin was positive in only 10% of the cells. The preoperative elevated concentrations of catecholamine in the urinalysis showed a marked decrease after surgery. Based on these findings, the tumour was diagnosed as a functional paraganglioma of the gall bladder. The patient has undergone regular thoracic radiographs and ultrasound examinations and, until 431 days after surgery, has shown no signs of metastases or recurrences. Based on our literature search, we report the first case of functional paraganglioma of the gall bladder in a dog.

Imaging update on gallbladder adenomyomatosis and its mimics.

Radiologists across many imaging modalities commonly encounter gallbladder adenomyomatosis. The classic imaging appearances of gallbladder adenomyomatosis are well described and confirm benignity. However, in clinical practice, adenomyomatosis can be challenging to differentiate from other gallbladder pathologies that require cholecystectomy. In this article, we describe the common and uncommon appearances of gallbladder adenomyomatosis on multimodality imaging, helping differentiate adenomyomatosis from non-benign gallbladder abnormalities. Accurately differentiating adenomyomatosis from its mimics provides the surgical team with important clinical and surgical management information, improving patient outcomes.

Ultrasound-guided percutaneous microwave ablation of gallbladder polyps: A case report.

RATIONALE: Gallbladder polyps are a general term for localized lesions in which the gallbladder wall protrudes into the gallbladder cavity, and benign lesions are common. Although current guidelines recommend cholecystectomy for gallbladder polyps ≥ 10 mm in size, the probability of finding cancer in postoperative pathological specimens is low. We should avoid unnecessary cholecystectomy and treat polyps with gallbladder preservation. Microwave ablation is safe and effective for the treatment of solid lesions, and can inactivates polyps while preserving gallbladder. Hence, we report a case of ultrasound-guided percutaneous microwave ablation of gallbladder polyps. PATIENT CONCERNS: A 72-year-old female patient had previously diagnosed a gallbladder polyp, but it was not taken seriously. Recently, the patient had occasional right upper abdominal discomfort and a desire to preserve gallbladder. DIAGNOSES: Ultrasound showed a medium hyperechoic papillary protrusion in the gallbladder without echo behind, and the changed position did not move. Contrast-enhanced ultrasound (CEUS) showed no malignant signs. The diagnosis was a gallbladder polyp. INTERVENTIONS: The bile is drained and the drainage tube is fixed under real-time ultrasound guidance, then the gallbladder cavity is flushed and filled. Saline was injected between the serous and mucosal layers of the gallbladder to form an "edema band" to protect the gallbladder wall. Then, ultrasound-guided biopsy of gallbladder polyps was performed and sent for histological examination. Finally, the microwave needle was inserted into the target area under real-time ultrasonic guidance, and ablation was performed for 3 minutes (20 W). Postoperative CEUS: No significant enhancement was observed in the lesion. OUTCOMES: Within 6 months of follow-up, the patient's gallbladder systolic function was normal, and there was no discomfort and no recurrence. The lesion reduction rate reached 100% at 1 week after surgery. LESSONS: Ultrasound guided percutaneous microwave ablation of gallbladder polyps not only preserves the gallbladder but also inactivates the polyps without affecting the systolic function of the gallbladder, which provides a new idea for the treatment of gallbladder polyps.

The risk and predictors of gallbladder cancer in patients with gallbladder polyps: A retrospective cohort study with an insight into confounding by indication.

BACKGROUND AND AIM: We aimed to determine the risk and predictors of gallbladder cancer in all individuals with gallbladder polyps (GP) including those who did not have cholecystectomy. METHODS: The STROCSS guideline was followed to conduct a retrospective cohort study. All individuals with GP between 2010 and 2019 were followed up to determine the risk and predictors of gallbladder cancer. The primary outcomes were gallbladder cancer and gallbladder dysplasia, and the secondary outcomes included polyp growth rate and polyp disappearance rate. Binary logistic regression analysis and receiver operating characteristic curve analysis were conducted to evaluate the outcomes. RESULTS: Analysis of 438 patients showed risk of gallbladder cancer was 0.7% in all polyps (0% in polyps < 10 mm; 5.9% in polyps ≥ 10 mm). The risk of gallbladder dysplasia or cancer was 1.1% in all polyps (0% in polyps < 10 mm; 10% in polyps ≥ 10 mm). The polyp size (P = 0.0001) was predictor of cancer; however, patient's age (P = 0.1085), number of polyps (P = 0.9983), symptomatic polyps (P = 0.3267), and change in size (P = 0.9012) were not. Size of 21 mm was cut-off for risk of cancer (area under the curve [AUC]: 0.995, P < 0.001) and 11.8 mm for risk of dysplasia or cancer (AUC: 0.986, P < 0.001). The mean polyp growth rate was 0.3 mm/year and polyp disappearance rate was 16%. CONCLUSIONS: The GP size remains the only predictor of malignant changes regardless of patient's age, patient's symptoms and number of polyps. The polyp growth rate is unremarkable, and a significant proportion disappears during follow-up. We changed our follow-up protocol with reduced number of scans and early discharge policy.

An incidental traditional serrated adenoma of the gallbladder: A case report.

Serrated lesions outside the low digestive tract are scarce, with only two traditional serrated adenomas (TSA) reported in the gallbladder, with limited information about the serrated pathway outside the colon. Our case was an incidental finding in a patient undergoing surgery to treat a cholecystitis, when a polypoid lesion was observed. The epithelium formed gland structures with ectopic crypts, serrated slits and eosinophilic cytoplasm. MUC4 and MUC5A were positive, but mismatch repair proteins (MSI) retained nuclear staining. BRAF showed a not mutated profile and NRAS/KRAS was inconclusive due to the absence of remaining tissue. MSI and CpG island (CIMP), the most common genetic hallmarks of the serrated pathway, have been proven in gallbladder carcinomas, although serrated polyps are not recognized as premalignant precursors. Hereby we report one TSA of the gallbladder without the usual genetic drivers. A larger evidence is needed to improve the diagnosis and management.

Circulating Tumor Cells are an Independent Risk Factor for Poor Prognosis in Patients with Gallbladder Adenocarcinoma.

BACKGROUND: The study aimed to evaluate the prognostic impact of circulating tumor cells (CTCs) in patients with gallbladder adenocarcinoma after resection. MATERIALS AND METHODS: Between January 2018 and January 2021, 101 consecutive patients with gallbladder adenocarcinoma were included. CTCs were detected and enumerated using the CanPatrol® technique. The follow-up period ended in January 2023. The cancer-specific survival (CSS) and disease-free survival (DFS) were calculated using log-rank and Cox regression analyses. RESULTS: CTCs were detected positively in 61.54% (8/13) of the patients in the non-operation group and 13.64% (12/88) in the operation group. In the operation group, the median CSS for CTCs-positive and CTCs-negative patients was 5.0 and 9.5 months (P < 0.001), respectively, and DFS was 2.8 and 5.0 months at stage III (P < 0.001), respectively. In the non-operation group, the median CSS for CTCs-positive and CTCs-negative patients was 3.5 and 6.5 months (P = 0.0031), respectively. The median CSS for CTCs-positive patients in the operation group was similar to that in the non-operation group (P = 0.67). Multivariate analyses showed that positive CTCs was an independent risk factor for poor CSS (HR 0.066, 95% CI 0.021-0.206, P < 0.001) as well as lymph infiltration (HR 0.320, 95% CI 0.110-0.930, P = 0.036), without R0 curative resection (HR 7.520, 95% CI 2.100-26.931, P = 0.002), and without adjuvant chemotherapy (HR 7.730, 95% CI 2.416-24.731, P < 0.001). CONCLUSION: Positive CTCs was an independent predictor of poor prognosis after resection in patients with gallbladder adenocarcinoma. Preoperative detection of CTCs may play an important guiding role in formulating treatment strategies for these patients.

Clinicopathologic characterization of gallbladder graft-versus-host disease in the pediatric population.

Graft-versus-host disease (GVHD) is a common and important complication of allogenic hematopoietic cell transplantation. The cardinal histologic feature of GVHD in the gastrointestinal tract is the presence of apoptotic bodies. To date, no study has evaluated the pathologic characteristics of gallbladder GVHD (GB-GVHD). In this study, we sought to describe their clinicopathologic features in a cohort of pediatric patients and compared them to a control group composed of 10 and 15 recent cases of acute and chronic cholecystitis, respectively. A total of 6 GB-GVHD cases were included, 5 cholecystectomies and 1 autopsy case(s), presenting in 2 boys and 4 girls, with a mean age of 6.7 years (1.5-18.6). The median days post-transplant to presentation was 261 (40-699), and all cases had GVHD involving other organs. GB-GVHD compared to the control groups was significantly associated with a younger age (P = .019), presence of apoptotic bodies and higher number of apoptotic bodies in 10 continuous mucosal folds and in 100 and 500 epithelial cells (all P < .001), and increased number of intraepithelial lymphocytes per 100 epithelial cells (P < .001). All patients were treated for GVHD with half of them achieving treatment response. Besides the autopsy case, all patients are alive with a median follow-up time of 45 months (4-212). The cause of death for the autopsy case was sepsis due to Pseudomonas aeruginosa. In our experience, the presence of both increased apoptotic bodies and intraepithelial lymphocytes in the gallbladder of hematopoietic cell transplantation patients should raise concern for GB-GVHD.