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.

Global, regional, and national burden of gallbladder and biliary diseases from 1990 to 2019

BACKGROUND Gallbladder and biliary diseases(GABDs)are a major public health issue.AIM To analysis the cause-specific incidence,prevalence,and years lived with disability(YLDs)and its temporal trends of GABDs at the global,regional,and national level.Data on GABD were available from the Global Burden of Disease study 2019.METHODS The estimated annual percentage change(EAPC)was used to quantify temporal trend in GABD age-standardized incidence rates(ASIRs),age-standardized prevalence rate(ASPR),and age-standardized YLD rate(ASYR)by region,sex.We analyzed the relationship between the GABD burden and country development level using the human development index(HDI).RESULTS In 2019,the incident cases of GABD were 52003772,with an ASIR of 63432/100000 population.Globally,the number of incident cases and ASIR of GABD increased 97%and 58.9%between 1990 and 2019.Although,the ASPR and ASYR decreased from 1990 to 2019,the number of prevalent and YLDs cases increased.The highest ASIR was observed in Italy,and the highest ASPR and ASYR was observed in United Kingdom.The highest burden of GABD was found in low-SDI region,and the burden in female was significantly higher than males.A generally negative correlation(ρ=-0.24,P<0.05)of GABD with the EAPC and human development index(HDI)(in 2021)were observed for ASIR.What’s more,no correlation in ASPR(ρ=-0.06,P=0.39)and ASYR(ρ=-0.07,P=0.36)of GABD with the EAPC and HDI(in 2021)were observed,respectively.CONCLUSION GABD remain a major global public health challenge;however,the burden of GABD varies geographically.Globally,the number of incident cases and ASIR of GABD increased between 1990 and 2019.The results of our study provide insight into the global disease burden of GABD and may assist policymakers in formulating effective policies to mitigate modifiable risk factors.

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.

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

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

Imaging-based algorithmic approach to gallbladder wall thickening

Gallbladder(GB) wall thickening is a frequent finding caused by a spectrum of conditions. It is observed in many extracholecystic as well as intrinsic GB conditions. GB wall thickening can either be diffuse or focal. Diffuse wall thickening is a secondary occurrence in both extrinsic and intrinsic pathologies of GB, whereas, focal wall thickening is mostly associated with intrinsic GB pathologies. In the absence of specific clinical features, accurate etiological diagnosis can be challenging. The survival rate in GB carcinoma(GBC) can be improved if it is diagnosed at an early stage, especially when the tumor is confined to the wall. The pattern of wall thickening in GBC is often confused with benign diseases, especially chronic cholecystitis, xanthogranulomatous cholecystitis, and adenomyomatosis. Early recognition and differentiation of these conditions can improve the prognosis. In this minireview, the authors describe the patterns of abnormalities on various imaging modalities(conventional as well as advanced) for the diagnosis of GB wall thickening. This paper also illustrates an algorithmic approach for the etiological diagnosis of GB wall thickening and suggests a formatted reporting for GB wall abnormalities.

Gallbladder cancer:Historical treatment and new management options

Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with minimally invasive techniques,the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease.Although the treatment remains mostly surgical,newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease.We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.

Expression of pituitary adenylate cyclase-activating polypeptide 1 and 2 receptor mRNA in gallbladder tissue of patients with gallstone or gallbladder polyps

AIM： To detect the expression of pituitary adenylate cyclase-activating polypeptide receptor i （VPCAPrR） and VPCAP2-R mRNA in gallbladder tissues of patients with gallstone or gallbladder polyps. METHODS： The expression of VPCAP1-R and VPCAP2-R mRNA in gallbladder tissues was detected in 25 patients with gallstone, 8 patients with gallbladder polyps and 7 donors of liver transplantation by reverse transcription polymerase chain reaction （RT-PCR）. RESULTS： The VPCAP2-R mRNA expression level in the control group （1.09±0.58） was lower than that in the gallbladder polyp group （1.64±0.56） and the gallstone group （1.55±0.45） （P〈0.05） while the VPCAP1-R mRNA expression level in the control group （1.15 ±0.23） was not apparently different from that in the gallbladder polyp group （1.28±0.56） and the gallstone group （1.27± 0.38）. CONCLUSION： The abnormal expression of VPCAP2-R mRNA in gallbladder tissue may play a role in the formation of gallbladder stone and gallbladder polyps.

Diagnosis of Tumor-Like Polypoid Lesions of Gallbladder by Serum Proteomic Fingerprint

Objective： To search the specific serum proteins in tumor-like polypoid lesions of the gallbladder（PLG） patients. Methods： Surface enhanced laser desorption/ionization time of flight mass spectrometry （SELDI-TOF-MS） technique and WCX Magnetic Beads were used to detect the serum proteomic fingerprint of 23 patients with tumor-like PLG, 21 patients with non tumor-like PLG and 26 normal persons. Biomarker Wizard and Biomarker Patterns Software were used in combination to analyze the data. Results： In the preliminary screening, 22 representative specific proteins for tumor-like PLG were found. Seven specific proteins showed increased expression and 15 specific proteins showed decreased expression in the tumor-like PLG patients. Three specific proteins are selected for the diagnosis of the tumor-like PLG.. Conclusion： SELDI-TOF-MS technique can be used to select specific proteins for tumor-like PLG patients, which may be useful for the diagnosis of the tumor-like PLG and the differential diagnosis with the non tumor-like PLG.

The effect of cholecystectomy on the risk of colorectal cancer:A systematic review and meta-analysis

Objective:Some studies have found that cholecystectomy may increase the risk of colorectal cancer(CRC),while others have reached inconsistent conclusions.We thus performed a systematic review and meta-analysis to assess the incidence rate of CRC after cholecystectomy for patients with gallstones or gallbladder diseases,and whether the geographical location of the patients affected the results.Methods:We systematically searched PubMed,Embase,and Cochrane for studies reporting changes in the incidence rate of CRC after cholecystectomy published before January 12,2023.Our main endpoint wasthe occurrence of CRC Data were extracted and pooled,and the relative risk(RR)and 95%confidence interval(CI)were calculated.We assessed pooled data using a random-effects model.Results:In total,477 articles were identifled,and 6 articles were eligible,including 7 studies thatincluded 797,917 participants.Overall,the summarized research results showed that the risk of CRC was reduced in patients with gallbladder diseases who underwent cholecystectomy(RR:0.80,95%C:0.65 to0.99,p=0.040;I^(2)=85.0%).In the subgroup analysis based on different geographical locations,chole-cystectomy was not associated with the nisk of CRC in the Western population(RR:0.90,95%C:0.65 to 1.25.p=0.522;I^(2)=86.5%),but there was a negative corelation between cholecystectomy and the risk of CRC(RR:0,66,95%Cl:0.60 to 0,73,p=0.000)in the Chinese population Conclusions:Our findings support that for patients with gallstones or gallbladder diseases,the incidence of CRC after cholecystectomy is lower than that of patients who do not undergo cholecystectomy.

Mirizzi syndrome:History,current knowledge and proposal of a simplified classification

Chronic complications of symptomatic gallstone disease, such as Mirizzi syndrome, are rare in Western developed countries with an incidence of less than 1% a year. The importance and implications of this condition are related to their associated and potentially serious surgical complications such as bile duct injury, and to its modern management when encountered during laparoscopic cholecystectomy. The pathophysiological process leading to the subtypes of Mirizzi syndrome has been explained by means of a pressure ulcer caused by an impacted gallstone at the gallbladder infundibulum, leading to an inflammatory response causing first external obstruction of the bile duct, and eventually eroding into the bile duct and evolving to a cholecystocholedochal or cholecystohepatic fistula. This article reviews the life of Pablo Luis Mirizzi, describes the earlier and later descriptions of Mirizzi syndrome, discusses the pathophysiological process leading to the development of these uncommon fistulas, reviews the current diagnostic modalities and surgical approaches and finally proposes a simplified classification for Mirizzi syndrome intended to standardize the reports on this condition and to eventually develop a consensual surgical approach to this unexpected and seriously dangerous condition.

Cholecystoenteric fistula with and without gallstone ileus: A case series

Background: A cholecystoenteric stula (CEF) is an uncommon complication of gallstone disease. The aim of this study was to present our experience of a series of patients with CEF, presenting with or without gallstone ileus, along with their surgical outcomes. Methods: From 2015 to 2018, 3245 consecutive patients underwent cholecystectomy for gallbladder disease at our institution, of which 15 were diagnosed with a CEF. All electronic medical records were retrospectively reviewed. Results: Fifteen patients presented with CEF. Ten patients presented cholecystoduodenal stula, four pa- tients cholecystocolonic, and one patient cholecystogastric counterparts. Twelve patients were female. The median patient age was 61 years (range 33 86 years). Five patients presented with gallstone ileus treated by laparotomy and enterolithotomy. In ten patients, a laparoscopic approach was attempted, but conversion to open surgery was necessary for eight of them. The median operative time was 140 min (range 60 240 min), and the median operative blood loss was 50 mL (range 10600mL). The procedure-related morbidity and mortality rates were 13.3% and 6.7%, respectively. Conclusions: There is no consensus on the best treatment modality for a CEF, as the treatment outcome is mostly dependent on the surgeon’s expertise and the patient’s condition. Not all CEFs are accompanied by gallstone ileus. For such case, the main purpose is to resolve the intestinal obstruction and, unless necessary, avoidance of the gallbladder area.

Health-related quality of life outcomes after cholecystectomy

Gallbladder diseases are very common in developed countries. Complicated gallstone disease represents the most frequent of biliary disorders for which surgery is regularly advocated. As regards, cholecystectomy represents a common abdominal surgical intervention; it can be performed as either an elective intervention or emergency surgery, in the case of gangrene, perforation, peritonitis or sepsis. Nowadays, the laparoscopic approach is preferred over open laparotomy. Globally, numerous cholecystectomies are performed daily; however, little evidence exists regarding assessment of post-surgical quality of life (QOL) following these interventions. To assess post-cholecystectomy QOL, in fact, documentation of high quality care has been subject to extended discussions, and the use of patientreported outcome satisfaction for quality improvement has been advocated for several years. However, there has been little research published regarding QOL out-comes following cholecystectomy; in addition, much of the current literature lacks systematic data on patientcentered outcomes. Then, although several tools have been used to measure QOL after cholecystectomy, diffi culty remains in selecting meaningful parameters in order to obtain reproducible data to reflect postoperative QOL. The aim of this study was to review the impact of surgery for gallbladder diseases on QOL. This review includes Medline searches of current literature on QOL following cholecystectomy. Most studies demonstrated that symptomatic patients profi ted more from surgery than patients receiving an elective intervention. Thus, the gain in QOL depends on the general conditions before surgery, and patients without symptoms profi t less or may even have a reduction in QOL.

Double-blind randomized sham controlled trial of intraperitoneal bupivacaine during emergency laparoscopic cholecystectomy

BACKGROUND: Intraperitoneal local anesthesia (IPLA) during elective laparoscopic cholecystectomy (el-LC) decreases post-operative pain. None of the studies have explored the efficacy of IPLA at emergency laparoscopic cholecystectomy (em-LC). A longer operative duration, the greater frequency of washing, and the inflammation associated with cholecystitis or pancreatitis are a few reasons why it cannot be assumed that a benefit in pain scores will be seen in em-LC with IPLA. This study was undertaken to assess the efficacy of IPLA in patients undergoing em-LC. METHODS: Double-blind randomized sham controlled trial was conducted of 41 consecutive subjects undergoing em-LC. IPLA was delivered by a combination of injection to the diaphragmatic and topical wash over the liver and gallbladder with bupivacaine or saline. The primary outcome was visual analogue scale pain scores until discharge. Secondary outcomes included pain scores in theatre recovery and analgesic consumption. RESULTS: One patient had a procedure converted to open and was excluded. There was no significant difference in pain scores in the ward or theatre recovery. Analgesic use, respiratory rate, oxygen saturation, duration to ambulation, eating, satisfaction scores, and time to discharge were comparable between the two groups. CONCLUSIONS: IPLA during em-LC does not influence postoperative pain. Other modalities of analgesia should be explored for decreasing the interval between diagnosis of acute admission and em-LC.

ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones

AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.

Risk Prediction Model of Gallbladder Disease in Shanghai Middle-Aged and Elderly People Based on Neural Networks

This paper discusses the risk factors related to gallbladder disease in Shanghai,improves the accuracy of risk prediction,and provides a theoretical basis for scientific diagnosis and universality of gallbladder disease.We selected 3462 data of middle-aged and elderly health check-up patients in a general hospital in Shanghai,and divided into gallbladder disease group according to color doppler ultrasound diagnosis results.Single-factor analysis screened out 8 important risk factors,which were used as an analysis variable of multi-layer perceptron neural network and binary logistic regression to construct the prediction model of gallbladder disease.The prediction accuracy of the multi-layer perceptron neural network risk prediction model is 76%.The area under the receiver operating characteristic curve(AUC)is 0.82,the maximum Youden index is 0.44,the sensitivity is 79.51,and the specificity is 64.23.The prediction accuracy of the multi-layer perceptron neural network model is better than that of the binary logistic regression prediction model.The overall prediction accuracy of the binary logistic regression prediction model is 75.60%,the AUC is 0.81,the maximum Youden index is 0.42,the sensitivity is 74.48,and the specificity is 57.60.In the objective risk prediction of gallbladder disease in middle-aged and elderly people in Shanghai,the risk prediction model based on the multi-layer perceptron neural network has a better prediction performance than the binary logistic regression model,which provides a theoretical basis for preventive treatment and intervention.