Sphincter of Oddi dysfunction and bile duct microlithiasis in acute idiopathic pancreatitis

Although there are numerous causes of acute panc-reatitis, an etiology cannot always be found. Two potential etiologies, microlithiasis and sphincter of Oddi dysfunction, are discussed in this review. Gallbladder microlithiasis, missed on transcutaneous ultrasound, is reported as the cause of idiopathic acute pancreatitis in a wide frequency range of 6%-80%. The best diagnostic technique for gallbladder microlithiasis is endoscopic ultrasound although biliary crystal analysis and empiric cholecystectomy remain as reasonable options. In contrast, in patients who are post-cholecystectomy, bile duct microlithiasis does not appear to have a role in the pathogenesis of acute pancreatitis. Sphincter of Oddi dysfunction is present in 30%-65% of patients with idiopathic acute recurrent pancreatitis in whom other diagnoses have been excluded. It is unclear if this sphincter dysfunction was the original etiology of the first episode of pancreatitis although it appears to have a causative role in recurring episodes since sphincter ablation decreases the frequency of recurrent attacks. Unfortunately, this conclusion is primarily based on small retrospective case series; larger prospective studies of the outcome of pancreatic sphincterotomy for SOD-associated acute pancreatitis are sorely needed. Another problem with this diagnosis and its treatment is the concern over potential procedure related complications from endoscopic retrograde cholangiopancreatography (ERCP), manometry and pancreatic sphincterotomy. For these reasons, patients should have recurrent acute pancreatitis, not a single episode, and have a careful informed consent before assessment of the sphincter of Oddi is undertaken.

Biliary microlithiasis,sludge,crystals, microcrystallization,and usefulness of assessment of nucleation time

BACKGROUND:The process of microcrystallization,its sequel and the assessment of nucleation time is ignored.This systematic review aimed to highlight the importance of biliary microlithiasis,sludge,and crystals,and their association with gallstones,unexplained biliary pain,idiopathic pancreatitis, and sphincter of Oddi dysfunction.DATA SOURCES:Three reviewers performed a literature search of the PubMed database.Key words used were'biliary microlithiasis','biliary sludge','bile crystals','cholesterol crystallisation','bile microscopy','microcrystal formation of bile','cholesterol monohydrate crystals','nucleation time of cholesterol','gallstone formation','sphincter of Oddi dysfunction'and'idiopathic pancreatitis'.Additional articles were sourced from references within the studies from the PubMed search.RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease,7%to 79%with idiopathic pancreatitis,83%with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function.Overall,the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a specificity of 100%.In idiopathic pancreatitis,the presence of microcrystals ranges from 47%to 90%.A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100%for cholesterol gallstone disease.CONCLUSIONS:Biliary crystals are associated with gallstone disease,idiopathic pancreatitis,sphincter of Oddi dysfunction, unexplained biliary pain,and post-cholecystectomy biliary pain.Pathways of cholesterol super-saturation,crystallisation, and gallstone formation have been described with scientificsupport.Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.

A rare diagnosis:testicular dysgenesis with carcinoma in situ detected in a patient with ultrasonic microlithiasis

A rare case is presented where a dysgenetic testis with microinvasive carcinoma in situ （CIS, also known as intratubular germ cell neoplasm of unclassified type [IGCNU] and testicular intraepithelial neoplasia [TIN]） with microinvasion to rete testis and the interstitial tissue was found in a 32-year-old man presenting with mild scrotal pain and ultrasonic testicular microlithiasis. Knowledge of the association of ultrasound and CIS is important to diagnose patients at the stage prior to development of an overt germ cell tumor. The patient had three of four disorders considered symptoms of the testicular dysgenesis syndrome （TDS）： a dysgenetic left testicle with CIS, a mild left-sided cryptorchidism （high positioned scrotal hypotrophic testis） and a slightly reduced semen quality. Therefore, it should be kept in mind that a patient with one TDS symptom may harbour the other, even CIS or testicular cancer. Accordingly, patients with one TDS symptom ought to be examined for the presence of the others, and if more that one is present, extra concern is warranted.

Single-lung transplantation for pulmonary alveolar microlithiasis: A case report

BACKGROUND Pulmonary alveolar microlithiasis(PAM)is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths.Currently,effective therapeutics for PAM are not available,and the only treatment for end-stage lung disease is lung transplantation(LuTx).Further,there are few reports that focus on LuTx for the treatment of PAM,and the follow-up reports of postoperative imaging are even rarer.CASE SUMMARY A 52-year-old man presented to Shanghai Pulmonary Hospital in 2017 after experiencing shortness of breath and exacerbation.The patient was diagnosed with PAM and referred for single-LuTx(SLuTx)on March 14,2018.Preoperative imaging results from a chest X-ray demonstrated bilateral,diffuse,symmetrical,sandstorm-like radiopaque micronodules,and pneumothorax and a computed tomography scan revealed minute,calcified military nodules in both lungs.We performed a left SLuTx,and intraoperative pathology was consistent with PAM.One week after surgery,a chest X-ray revealed slight exudation of the left lung,and one month later,the left transplanted lung exhibited good dilation,mild pulmonary perfusion injury with local infection,and left pleural effusion.Fiberoptic bronchoscopy revealed left hyperplastic granulation at the left bronchial anastomosis.Multiple sputum cultures suggested the presence of Klebsiella pneumoniae and Acinetobacter baumannii.The last follow-up was conducted in April 2019;the patient recovered well.CONCLUSION This case presents the imaging findings of a patient with PAM before and after LuTx and confirms the effectiveness of LuTx for the treatment of this disease.

Update on diagnosis and treatment of pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis(PAM)(MIM265100)is a rare disease characterized by the diffuse deposit of microlithiasis in alveolar spaces.PAM could occur worldwide with high prevalence in Asia and Europe.Familial occurrence indicates its autosomal recessive trait and the SLC34A2 gene was identified as the responsible gene for the disease.In spite of the versatile mutation sites in patients from other countries,exon 7and exon 8 might be the most liable gene in Chinese and Japanese patients.Most mutations caused the premature termination of proteins and produced truncated proteins,leading to the blocking of the recycling and degrading of outdated surfactant which is full of phospholipids.The most outstanding clinical feature of PAM is the discrepancy between the paucity of symptoms and the degree of pulmonary involvement.Diagnosis is easy to establish based on typical chest radiograph image and nuclear medicine improves its early diagnosis and active evaluation.Pathology of the unique intra-alveolar lamellar microliths gives strong support for diagnosis.No effective treatment is considered valid currently.However,lung transplantation is effective for advanced-stage patients,and long term treatment of disodium etidronate seems promising.

Correlation of testicular reproductive tumor related genes in semen of patients with testicular microlithiasis

Objective:To investigate the expression of testicular tumor-related genes in the semen of patients with microlithiasis,as well as the semen concentration in patients with microlithiasis.Methods:Retrospective analysis of 2018/6-2019/6 male in our hospital clinic examination of patients with testicular color to exceed,semen specimen were collected,30 patients with testicular micro stone disease group of 15 cases,control group in 15 cases,the process of semen automatic analyzer to detect sperm concentration,by rt-pcr and Western Blot respectively detect testicular cancer related gene(KITLG KIT ligand(gene),SPRY4(sprouty RTK signaling 4)antagonist)mRNA and protein expression.Results:The semen concentration(17.31±0.92)×10-6/ml in the microstone group was lower than that in the control group(29.26±1.57)×10-6/ml.The mRNA expression of semen(KITLG,SPRY4)in the microstone group was higher than that in the control group,and the difference was statistically significant.The protein expression of semen(KITLG,SPRY4)in the microstone group was higher than that in the control group,and the difference was statistically significant.Conclusion:The semen concentration of testicular microlithiasis decreased,but the expression of seminal testicular tumor genes(KITLG,SPRY4)increased.

Pulmonary alveolar microlithiasis： an interesting case report with systematic review of Indian literature

Pulmonary alveolar microlithiasis is a rare disease characterized by intra-alveolar presence of microliths. This study reports an interesting case of pulmonary alveolar microlithiasis and provides a systematic review of cases reported from India. A 23-year-old female presented with a history of cough, wheeze, chest pain, and episodic wheeze for five months. Pulmonary function tests demonstrated an obstructive pattern, and chest X- ray showed fine micronodular opacities predominantly involving the middle and lower zones of both lungs. Transbronchial lung biopsy revealed the diagnosis. She responded well to inhaled steroid therapy. A systematic review of literature was performed and identified 73 cases of pulmonary alveolar microlithiasis reported from India. The mean （SD） age of the patients was 28.8 （14.9） years, with an almost equal male：female ratio. Many patients were asymptomatic at presentation. Breathlessness and cough were the most common symptoms, and the disease progressed into respiratory failure associated with cor pulmonale. About one-third of the cases were initially misdiagnosed and treated as pulmonary tuberculosis. Extra-pulmonary manifestations and co- morbidities were also evident in our series. This systematic review helps to determine epidemiological and clinical characteristics of pulmonary alveolar microlithiasis. Further research is needed to elucidate the etiopathogenesis, diagnosis, and therapeutic options, which are beneficial in developing and identifying cost- effective treatment for pulmonary alveolar microlithiasis.

Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis

Testicular microlithiasis （TM） is one of the symptoms of testicular dysgenesis syndrome （TDS）. TM is particularly interesting as an informative marker of testicular germ cell tumors （TGCTs）. KIT ligand gene （KITLG）, BCL2 antagonist/killer 1 （BAK1）, and sprouty RTK signaling antagonist 4 （SPRY4） genes are associated with a high risk of TGCTs, whereas bone morphogenetic protein 7 gene （BMP7）, transforming growth factor beta receptor 3 gene （TGFBR3）, and homeobox D cluster genes （HOXD） are related to TDS. Using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis, we investigated allele and genotype frequencies for KITLG （rs995030, rs1508595）, SPRY4 （rs4624820, rs6897876）, BAK1 （rs210138）, BMP7 （rs388286）, TGFBR3 （rs12082710）, and HOXD （rs17198432） in 142 TGCT patients, 137 TM patients, and 153 fertile men （control group）. We found significant differences in the KITLG GG_rs995030 genotype in TM （P= 0.01） and TGCT patients （P = 0.0005） compared with the control. We also revealed strong associations between KITLGrs1508595 and TM （G allele, P = 0.003; GG genotype, P= 0.01） and between KITLG_rs1508595 and TGCTs （G allele, P-- 0.0001; GG genotype, P = 0.0007）. Moreover, there was a significant difference in BMP7_rs388286 between the TGCT group and the control （T allele, P = 0.00004; TT genotype, P = 0.00006） and between the TM group and the control （T allele, P= 0.04）. HOXDalso demonstrated a strong association with TGCTs （rs17198432 A allele, P = 0.0001; AA genotype, P = 0.001）. Furthermore, significant differences were found between the TGCT group and the control in the BAK1_rs210138 G allele （P= 0.03） and the GG genotype （P= 0.01）. KITLG and BMP7genes, associated with the development of TGCTs, may also be related to TM. In summary, the KITLG GG_rs995030, GG_rs1508595, BMP7 TT_rs388286, HOXD AA_rs17198432, and BAK1 GG_rs210138 genotypes were associated with a high risk of TGCT development.

Similarities and differences between biliary sludge and microlithiasis: Their clinical and pathophysiological significances

The terms biliary sludge and cholesterol microlithiasis(hereafter referred to as microlithiasis)were originated from different diagnostic techniques and may represent different stages of cholesterol gall-stone disease.Although the pathogenesis of biliary sludge and microlithiasis may be similar,micro-lithiasis could be preceded by biliary sludge,followed by persistent precipitation and aggregation of solid cholesterol crystals,and eventually,gallstone formation.Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis,including total parenteral nutrition,rapid weight loss,pregnancy,organ transplantation,administration of certain medications,and a variety of acute and chronic illnesses.Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40%of patients,a cyclic pattern of disappearing and reappearing in about 40%,and progression to gallstones in nearly 20%.Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones,it is still a matter of controversy whether micro-lithiasis could eventually evolve to cholesterol gallstones.Biliary sludge and microlithiasis are asymp-tomatic in the vast majority of patients;however,they can cause biliary colic,acute cholecystitis,and acute pancreatitis.Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis.Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population.Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge.Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis.Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.

Incidence characteristics of testicular microlithiasis and its association with risk of primary testicular tumors in children: a systematic review and meta-analysis

Background To systematically evaluate the incidence characteristics of testicular microlithiasis(TM)in children and its association with primary testicular tumors(PTT).Methods A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA)statement.A priori protocol was registered in the PROSPERO database(CRD42018111119),and a literature search of all relevant studies published until February 2019 was performed.Prospective,retrospective cohort,or cross-sectional studies containing ultrasonography(US)data on the incidence of TM or the association between TM and PTT were eligible for inclusion.Results Of the 102 identified articles,18 studies involving 58,195 children were included in the final analysis.The overall incidence of TM in children with additional risk factors for FTT was 2.1%.In children,the proportion of left TM in unilateral cases was 55.7%,the frequency of bilateral TM was 69.0%,and proportion of classic TM was 71.8%[95%confidence interval(Cl)62.4-81.1%,P=0.0,72=0.0%].About 93.5%of TM remained unchanged,and newly detected PTT rate was very low(4/296)during follow-up.The overall risk ratio of TM in children with a concurrent diagnosis of PTT was 15.46(95%Cl 6.93-34.47,P<0.00001).Conclusions The incidence of TM in children is highly variable.Nonetheless,TM is usually bilateral,of the classic type,and remains stable or unchanged at follow-up.Pediatric patients with TM and contributing factors for PTT have an increased risk for PTT;however,there is no evidence to support mandatory US surveillance of children with TM.

Machine learning-based decision tool for selecting patients with idiopathic acute pancreatitis for endosonography to exclude a biliary aetiology

BACKGROUND Biliary microlithiasis/sludge is detected in approximately 30%of patients with idiopathic acute pancreatitis(IAP).As recurrent biliary pancreatitis can be prevented,the underlying aetiology of IAP should be established.AIM To develop a machine learning(ML)based decision tool for the use of endosonography(EUS)in pancreatitis patients to detect sludge and microlithiasis.METHODS We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed AP admitted to our tertiary care hospital between 2015 and 2020.Patients who did not receive EUS as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded.We trained supervised ML classifiers using H_(2)O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge.The predictor model was further validated in two independent retrospective cohorts from two tertiary care centers(117 patients).RESULTS Twenty-eight categorized patients’variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84[95%confidence interval(CI):0.791-0.9185],positive predictive value of 0.84,and negative predictive value of 0.80 in the identification cohort(218 patients).In the validation cohort,the robustness of the prediction model was confirmed with an accuracy of 0.76(95%CI:0.673-0.8347),positive predictive value of 0.76,and negative predictive value of 0.78(117 patients).CONCLUSION We present a robust and validated ML-based predictor model consisting of routinely recorded parameters at admission that can predict biliary sludge and microlithiasis as the cause of AP.

Role of endoscopic ultrasound in idiopathic pancreatitis

Recurrent acute pancreatitis(RAP) is defined based on the occurrence of two or more episodes of acute pancreatitis. The initial evaluation fails to detect the cause of RAP in 10%-30% of patients, whose condition is classified as idiopathic RAP(IRAP). Idiopathic acute pancreatitis(IAP) is a diagnostic challenge for gastroenterologists. In view of associated morbidity and mortality, it is important to determine the aetiology of pancreatitis to provide early treatment and prevent recurrence. Endoscopic ultrasound(EUS) is an investigation of choice for imaging of pancreas and biliary tract. In view of high diagnostic accuracy and safety of EUS, a EUS based management strategy appears to be a reasonable approach for evaluation of patients with a single/recurrent idiopathic pancreatitis. The most common diagnoses by EUS in IAP is biliary tract disease. The present review aims to discuss the role of EUS in the clinical management and diagnosis of patients with IAP. It elaborates the diagnostic approach to IAP in relation to EUS and other different modalities. Controversial issues in IAP like when to perform EUS, whether to perform after first episode or recurrent episodes, comparison among different investigations and the latest evidence significance are detailed.

Utility of endoscopic ultrasound in pancreatitis:A review

The close proximity of the endoscopic ultrasound probe to the pancreas results in superior spatial resolution compared to CT scan and MRI. In addition, endoscopic ultrasound (EUS) is a minimally invasive procedure that does not share the relatively high complication rate of ERCP. Due to these advantages, EUS has evolved into an important technique to assess pancreatobiliary disease. This review will discuss the role of EUS in patients with pancreatitis. The indications can be divided into acute pancreatitis and chronic pancreatitis. In acute pancreatitis, EUS is used to determine the etiology; in suspected chronic pancreatitis it is helpful to establish the diagnosis. Lastly, this review will discuss biliary pancreatitis with suspicion for persistent choledocholithiasis.