Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

AIM： To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS： Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power （×200） fields with the highest lymphatic vessel density （LVD）, termed ＂hot spots＂; were identified for each layer （mucosa, muscle layer, and perimuscular connective tissue）. In individual hot spots, the LVD and relative lymphatic vessel area （LVA） were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses. RESULTS： In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2, 35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively. Thus, both the LVD and LVA differed significantly （P 〈 0.001 and P 〈 0.001, respectively; KruskaI-Wallis test） among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most （98 of 108） of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer. CONCLUSION： The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 （tumor invading the perimuscular connective tissue） or more advanced gallbladder carcinoma.

An Alternative Approach to Sending All Gallbladders for Histology Following Cholecystectomy?

Background: The question of a selective approach to sending all gallbladders for histology following cholecystectomy has been postulated in many journals but as yet no guidelines have been published in light of such concern. This project will attempt to analyse and address the controversy surrounding sending all gallbladders for histology following cholecystectomy. Objective: To ascertain whether there is a feasible and safe alternative to sending all gallbladders to histology following cholecystectomy and to challenge such a hypothesis. Design: Retrospective study. Methods: Analysis of gallbladder pathology reports, patient medical records and computerised test results from cholecystectomies done in the last 5 years within the Lancashire Teaching Hospital Trust. Results: The alternative selective method based on pre-operative investigations and intra-operative macroscopic detail is shown to be significant (P < 0.05). Conclusion: The results from this study show that there is safe and efficient way of selecting which gallbladders are sent for histology based on age, pre-surgical suspicion and intra-operative macroscopic abnormalities.

Use of endoscopic ultrasound-guided gallbladder drainage as a rescue approach in cases of unsuccessful biliary drainage

This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.

New trends in diagnosis and management of gallbladder carcinoma

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

Heterotopic pancreas in the gallbladder:A case report

BACKGROUND Heterotopic pancreas(HP)refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas.HP occurs mostly in the stomach,duodenum,and colon,and rarely in the gallbladder.CASE SUMMARY A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years.An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder.The patient underwent a laparoscopic cholecystectomy,and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder.The patient had a favorable recovery and was discharged on postoperative day 3.She did not report any symptoms or complications at the 6-mo postoperative follow-up.Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy.CONCLUSION This case provides more information about HP in the gallbladder,a rare occurrence.

Natural history of asymptomatic gallbladder stones in clinic without beds:A long-term prognosis over 10 years

BACKGROUND Several studies have explored the long-term prognosis of patients with asymp-tomatic gallbladder stones.These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases.AIM To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities.METHODS We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022.When symptoms developed,patients were transferred to hospitals where appropriate treatment was possible.We investigated the asymptomatic and survival periods during the follow-up.RESULTS Among the 237 patients,214(90.3%)remained asymptomatic,with a mean asymptomatic period of 3898.9279±46.871 d(50-4111 d,10.7 years on average).Biliary complications developed in 23 patients(9.7%),with a mean survival period of 4010.0285±31.2788 d(53-4112 d,10.9 years on average).No patient died of biliary complications.CONCLUSION The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable.When the condition became symptomatic,the patients were transferred to hospitals with beds that could address it;thus,no deaths related to biliary complications were reported.This finding suggests that follow-up care in clinics without beds is possible.

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

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

Duplicated gallbladder with acute cholecystitis:a case of unusual presentation and diagnostic challenges

Anomalies in the gallbladder can lead to misidentifying anatomical structures,heightening the risk of complications in laparoscopic and open cholecystectomy procedures.Failure to recognize these variations increases the chances of iatrogenic bile duct injuries and other complications.

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

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

Radical cholecystectomy without liver resection for peritoneal side early incidental gallbladder cancer

Gallbladder cancer(GBC)is a rare disease with a poor prognosis.Simple cholecystectomy may be an adequate treatment only for very early disease(Tis,T1a),whereas reoperation is recommended for more advanced disease(T1b and T2).Radical cholecystectomy should have two fundamental objectives:To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes.However,recent studies have shown that compared with lymph node dissection alone,liver resection does not improve survival outcomes.The oncological roles of lymphadenectomy and liver resection is distinct.Therefore,for patients with incidental GBC without liver invasion,hepatic resection is not always mandatory.

Defining failure of endoluminal biliary drainage in the era of endoscopic ultrasound and lumen apposing metal stents

The role of endoscopy in pathologies of the bile duct and gallbladder has seen notable advancements over the past two decades.With advancements in stent technology,such as the development of lumen-apposing metal stents,and adoption of endoscopic ultrasound and electrosurgical principles in therapeutic endoscopy,what was once considered endoscopic failure has transformed into failure of an approach that could be salvaged by a second-or third-line endoscopic strategy.Incorporation of these advancements in routine patient care will require formal training and multidisciplinary acceptance of established techniques and collaboration for advancement of experimental techniques to generate robust evidence that can be utilized to serve patients to the best of our ability.

Use of indocyanine green fluorescence for triple gallbladder cholecystectomy: A case report

Triple gallbladder is a rare anatomical anomaly resulting from impaired embryological regression of the biliary tract during the 5th week of gestation.1 This entitywas first described by Huber during an autopsy in 1752,2 and the first clinical case was published by Boni et al in 1958.3 Since then,only 22 cases have been reported in the literature.4,5 The low incidence of this biliary tract anomaly and the nonspecific clinical presentation,usually biliary colic or cholecystitis,make a challenging clinical diagnosis.Multimodal imaging examination is required for confirmed diagnosis.

Endoscopic diagnosis and management of gallbladder carcinoma in minimally invasive era:New needs,new models

Gallbladder cancer(GBC)is a rare and lethal malignancy;however,it represents the most common type of biliary tract cancer.Patients with GBC are often diagnosed at an advanced stage,thus,unfortunately,losing the opportunity for curative surgical intervention.This situation leads to lower quality of life and higher mortality rates.In recent years,the rapid development of endoscopic equipment and techniques has provided new avenues and possibilities for the early and minimally invasive diagnosis and treatment of GBC.This editorial comments on the article by Pavlidis et al.Building upon their work,we explore the new needs and corresponding models for managing GBC from the endoscopic diagnosis and treatment perspective.

Current considerations for the surgical management of gallbladder adenomas

Gallbladder adenomas are rare lesions(0.5%)associated with potential malignant transformation,particularly with gallbladder adenomas that are≥1 cm in size.Early detection and management are crucial for preventing lethal carcinoma de-velopment.These polyps can often be distinguished from the more often nonneo-plastic cholesterol pseudopolyps(5%-10%),which are benign.Ultrasonography is the first-line tool for initial diagnosis and follow-up when indicated.The question is whether cholecystectomy is always necessary for all adenomas.The manage-ment of gallbladder adenomas is determined according to the size of the tumor,the growth rate of the tumor,the patient’s symptoms and whether risk factors for malignancy are present.Adenomas≥1 cm in size,an age>50 years and a familial history of gallbladder carcinoma are indications for immediate laparoscopic chole-cystectomy.Otherwise,ultrasound follow-up is indicated.For adenomas 6-9 mm in size,the absence of≥2 mm growth at 6 months,one year,and two years,as well as an adenoma sized<5 mm without existing risk factors indicates that no further surveillance is required.However,it would be preferable to individualize the management in doubtful cases.Novel interventional modalities for preserving the gallbladder need further evaluation,especially to determine the long-term outcomes.

Gallbladder carcinosarcoma with a poor prognosis: A case report

BACKGROUND Carcinosarcoma of the gallbladder is a rare malignant tumor with a very poor prognosis.To date,only approximately 100 patients have been reported in the English literature.The prognosis of this tumor type is poor,the preoperative diagnosis is difficult,and there is a possibility of a misdiagnosis.We present an unsuccessful case of carcinosarcoma of the gallbladder with a preoperative misdiagnosis and rapid early postoperative recurrence.Therefore,we have a deeper understanding of the poor prognosis of gallbladder carcinosarcoma(GBC)patients.CASE SUMMARY The patient is a 65-year-old male.He was admitted to the hospital because of right upper abdomen distending pain and discomfort for half a month.Abdominal magnetic resonance imaging revealed a polycystic mass in the right lobe of the liver and the fossa of the gallbladder.After admission,the patient was diagnosed with a liver abscess,which was treated by abscess puncture drainage.Obviously,this treatment was unsuccessful.Hepatectomy and cholecystectomy were performed one month after the puncture.Postoperative pathologic examination revealed carcinosarcoma of the gallbladder,and the resected specimen contained two tumor components.One month after surgery,the patient's tumor recurred in situ and started to compress the duodenum,resulting in duodenal obstruction and bleeding.The treatment was not effective.The patient died of gastrointestinal hemorrhage and hypovolemic shock.CONCLUSION Carcinosarcoma of the gallbladder is a rare malignant tumor that is easily misdiagnosed preoperatively and has a poor prognosis.

Cracking the silent gallstone code:Wait or operate?

The widespread availability of abdominal ultrasound has revealed the common occurrence of asymptomatic gallstones.While the treatment for symptomatic gallstones is clear,the benefits of minimally invasive laparoscopic cholecystectomy have sparked debate about the best approach to managing silent gallstones.The potential for asymptomatic gallstones to become symptomatic or lead to complications complicates the decision-making process regarding surgical intervention,as it's uncertain when or which patients might develop complications.Consequently,risk stratification appears to play a critical role in guiding decisions about silent gallstones.However,there is no definitive evidence to direct management,and a consensus-based on high-quality evidence is yet to be established.

Risk factors and survival prediction model establishment for prognosis in patients with radical resection of gallbladder cancer

BACKGROUND Gallbladder cancer(GBC)is the most common malignant tumor of the biliary system,and is often undetected until advanced stages,making curative surgery unfeasible for many patients.Curative surgery remains the only option for long-term survival.Accurate postsurgical prognosis is crucial for effective treatment planning.tumor-node-metastasis staging,which focuses on tumor infiltration,lymph node metastasis,and distant metastasis,limits the accuracy of prognosis.Nomograms offer a more comprehensive and personalized approach by visually analyzing a broader range of prognostic factors,enhancing the precision of treatment planning for patients with GBC.AIM A retrospective study analyzed the clinical and pathological data of 93 patients who underwent radical surgery for GBC at Peking University People's Hospital from January 2015 to December 2020.Kaplan-Meier analysis was used to calculate the 1-,2-and 3-year survival rates.The log-rank test was used to evaluate factors impacting prognosis,with survival curves plotted for significant variables.Single-factor analysis revealed statistically significant differences,and multivariate Cox regression identified independent prognostic factors.A nomogram was developed and validated with receiver operating characteristic curves and calibration curves.Among 93 patients who underwent radical surgery for GBC,30 patients survived,accounting for 32.26%of the sample,with a median survival time of 38 months.The 1-year,2-year,and 3-year survival rates were 83.87%,68.82%,and 53.57%,respectively.Univariate analysis revealed that carbohydrate antigen 19-9 expre-ssion,T stage,lymph node metastasis,histological differentiation,surgical margins,and invasion of the liver,ex-trahepatic bile duct,nerves,and vessels(P≤0.001)significantly impacted patient prognosis after curative surgery.Multivariate Cox regression identified lymph node metastasis(P=0.03),histological differentiation(P<0.05),nerve invasion(P=0.036),and extrahepatic bile duct invasion(P=0.014)as independent risk factors.A nomogram model with a concordance index of 0.838 was developed.Internal validation confirmed the model's consistency in predicting the 1-year,2-year,and 3-year survival rates.CONCLUSION Lymph node metastasis,tumor differentiation,extrahepatic bile duct invasion,and perineural invasion are independent risk factors.A nomogram based on these factors can be used to personalize and improve treatment strategies.

Benefits of endoscopic gallbladder stenting following percutaneous transhepatic gallbladder drainage

BACKGROUND Endoscopic transpapillary gallbladder drainage is challenging because of the complexity of the procedure and high incidence of adverse events(AEs).To overcome these problems,endoscopic gallbladder stenting(EGBS)after percutaneous transhepatic gallbladder drainage(PTGBD)can be effective,as it mitigates inflammation and adhesion.AIM To examine the benefits of EGBS after PTGBD to assess its efficacy and impact on AEs.METHODS We retrospectively analyzed data from 35 patients who underwent EGBS after PTGBD at a single center between January 2016 and December 2023.The primary outcomes were technical success and AEs,and the rate of recurrent cholecystitis was evaluated.In addition,the reasons for the failure of the procedure were identified.RESULTS Among the 35 patients,the technical success rate was 77.1%and the final contrast of the cystic duct was successful in 97.1%of patients.The incidence of early AEs was relatively low(11.4%),with no instances of cystic duct perforation.The rate of recurrent cholecystitis was 3.7%,and no other biliary events were observed.CONCLUSION EGBS after PTGBD may be significantly beneficial,with a substantial success rate and minimal AEs in both short-and long-term follow-ups.

Formation and rupture of liver hematomas caused by intrahepatic gallbladder perforation:A case report and review of literature

BACKGROUND Gallbladder perforation is a serious complication of acute cholecystitis.Such perforation is a rare but life-threatening situation that can lead to the formation and rupture of liver hematomas.Here,we report a case of a ruptured intrahepatic hematoma caused by intrahepatic gallbladder perforation,and we present a literature review.CASE SUMMARY A 70-year-old male was admitted to the hospital with a complaint of right upper quadrant abdominal pain,flustering and dizziness.The preoperative diagnosis was a ruptured malignant liver tumor,and the patient’s medical images and increased level of carbohydrate antigen-199 suggested that the gallbladder had been invaded.However,the tumor was proven to be a liver hematoma secondary to gallbladder perforation after surgery.The patient was discharged uneventfully on the fifteenth postoperative day.CONCLUSION Intrahepatic gallbladder perforation is difficult to diagnose preoperatively.Radiological examinations play a crucial role in the diagnosis but only for partial cases.Early diagnosis and appropriate surgery are key to managing this rare condition.

Spilled gallstone mimicking intra-abdominal seeding of gallbladder adenocarcinoma: A case report

BACKGROUND Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status.The gallstones may sometime be spilled into the peritoneal cavity,resulting in intra-abdominal ab-scess if the gallstones were not retrieved.The diagnosis of intra-abdominal ab-scess caused by unretrieved gallstone can usually be correctly identified in the routine imaging studies,such as abdominal ultrasonography or computed tomo-graphy(CT).Here we present a case of abscess formation from unretrieved gall-stone following laparoscopic cholecystectomy,which mimics the imaging findings of metastatic gallbladder ade-nocarcinoma.CASE SUMMARY This case described a 78-year-old man who received laparoscopic cholecystectomy and gallbladder adenocarcinoma was diagnosed after surgery.After adjuvant chemotherapy,the following up abdominal CT showed several small nodules at right upper abdomen and peritoneal carcinomatosis is considered.Repeated laparoscopic surgery for the excision of seeding tumor was conducted and the pathological diagnosis of the nodules and mass was inflammatory tissues and gallbladder stone.CONCLUSION Spilled gallstones are a common complication during laparoscopic cholecystectomy and some gallstones fail to be retrieved due to the size or the restricted view of laparoscopic surgery.For spilled gall bladder stones,surgeons may consider regular computerized tomography follow-up,and if necessary,laparoscopic examination can be used as a means of confirming the diagnostic and treatment.