Obeticholic acid as a second-line treatment for low phospholipid-associated cholelithiasis syndrome.

BACKGROUND: Low phospholipid-associated cholelithiasis (LPAC) syndrome is a rare genetic cause of hepatolithiasis. A pathogenic variant of the ABCB4 gene is reported in half of all patients. Ursodeoxycholic acid (UDCA) is the only drug approved. However, in some patients, UDCA fails to prevent recurrence of symptoms and complications. Experimental evidence suggests that agonists of the farnesoid-X receptor (FXR), the main transcription factor regulating ABCB4, may be beneficial in this context. AIM: To study the efficacy of obeticholic acid (OCA) in patients with LPAC syndrome with an inadequate response or intolerance to UDCA. METHODS: This was a retrospective study of patients with LPAC syndrome treated with OCA, a selective FXR agonist. RESULTS: We reviewed the records of five OCA-treated patients (4 women; median age 29; ABCB4 variant in 4; no hepatic fibrosis). All patients received OCA at an initial dose of 5 mg daily and then 10 mg daily for a median period of 36 months in combination with UDCA (4 patients) or as a monotherapy (one patient). There were no adverse effects reported. Four patients had improvement in their symptoms - three completely and one partially. One patient had no clinical benefit. Abnormalities of blood liver tests persisted in one patient despite resolution of symptoms. Radiological signs of hepatolithiasis persisted in three of the four patients who responded clinically to OCA. CONCLUSIONS: These preliminary observations suggest that OCA may have the potential to effectively treat LPAC syndrome in patients with inadequate response or intolerance to UDCA. Larger studies are needed to confirm these data.

Value of Music and Nitrous Oxide for Pain Control during Extracorporeal Shock Wave Lithotripsy (ESWL).

OBJECTIVES: To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients' subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz. RESULTS: Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group. CONCLUSIONS: The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high.

Silicotuberculosis with oesophagobronchial fistulas and broncholithiasis: a case report.

A 76-year-old woman was admitted to the hospital four times from November 2007 to June 2009. In this complex case, the patient had silicosis complicated by broncholithiasis, oesophagobronchial fistulas, and relapsed tuberculosis. She had worked as a stone crusher for 3 years and was exposed to a large amount of quartz dust. Barium oesophagography, gastroesophageal endoscopy, and biopsy suggested oesophageal-related chronic inflammation and ulceration, which may have caused the repeated oesophagobronchial fistulas. Bronchoscopy revealed a free broncholithiasis in the left mainstem bronchus. The patient was admitted a fourth time because of silicotuberculosis relapse. After 9 months of antituberculosis treatment, the patient recovered and was still clinically well at the time of this writing.

Silicotuberculosis with Esophagobronchial Fistula and Broncholithiasis.

A 69-year-old woman was admitted to hospital 4 times from November 2007 to June 2009. The patient had silicosis complicated by broncholithiasis, esophagobronchial fistula, and relapsed tuberculosis. She had worked as a stone crusher for 3 years and was exposed to a large amount of quartz dust. Barium esophagography, gastroesophageal endoscopy, and biopsy suggested esophageal-related chronic inflammation and ulcer, which probably caused the repeated esophagobronchial fistulas observed. Bronchoscopy revealed a free broncholithiasis in the left main bronchus. The patient was readmitted a fourth time, for the relapse of silicotuberculosis. After 9 months of antituberculous therapy, she was doing well until the recent last follow-up visit.

Effects of PDE5 Inhibitors and sGC Stimulators in a Rat Model of Artificial Ureteral Calculosis.

Urinary colics from calculosis are frequent and intense forms of pain whose current pharmacological treatment remains unsatisfactory. New and more effective drugs are needed to control symptoms and improve stone expulsion. Recent evidence suggested that the Nitric Oxide (NO) / cyclic guanosine monophosphate (cGMP)/phosphodiesterase type 5 (PDE5) system may contribute to ureteral motility influencing stone expulsion. We investigated if PDE5 inhibitors and sGC stimulators influence ureteral contractility, pain behaviour and stone expulsion in a rat model of ureteral calculosis. We investigated: a) the sex-specific PDE5 distribution in the rat ureter; b) the functional in vitro effects of vardenafil and sildenafil (PDE5 inhibitors) and BAY41-2272 (sGC stimulator) on induced ureteral contractility in rats and c) the in vivo effectiveness of vardenafil and BAY41-2272, alone and combined with ketoprofen, vs hyoscine-N-butylbromide alone or combined with ketoprofen, on behavioural pain indicators and stone expulsion in rats with artificial calculosis in one ureter. PDE5 was abundantly expressed in male and female rats' ureter. In vitro, both vardenafil and BAY41-2272 significantly relaxed pre-contracted ureteral strips. In vivo, all compounds significantly reduced number and global duration of "ureteral crises" and post-stone lumbar muscle hyperalgesia in calculosis rats. The highest level of reduction of the pain behaviour was observed with BAY41-2272 among all spasmolytics administered alone, and with the combination of ketoprofen with BAY41-2272. The percentage of stone expulsion was maximal in the ketoprofen+BAY41-2272 group. The NO/cGMP/PDE5 pathway is involved in the regulation of ureteral contractility and pain behaviour in urinary calculosis. PDE5 inhibitors and sGC stimulators could become a potent new option for treatment of urinary colic pain.

Broncholithiasis presenting as bronchiectasis and recurrent pneumonias.

A broncholith is defined as the presence of calcified material within a bronchus or within a cavity communicating with a bronchus. It is most frequently caused by Histoplasmosis or tuberculosis (TB) spp. Bronchial distortion, irritation and erosion by broncholiths can cause bronchiectasis, recurrent pneumonias and haemoptysis. We present a case of recurrent pneumonia due to a broncholith, which resolved conservatively with antibiotics. Owing to recurrent fevers and post obstructive pneumonias, a lobectomy or rigid bronchoscopic removal were considered but the patient was deemed not to be a candidate for general anaesthesia due to her comorbidities. Broncholiths are an uncommon cause of bronchiectasis and recurrent pneumonias. However, the wide range of symptoms and low clinical suspicion are the main reasons why a diagnosis can be delayed. Various treatment options are available and the choice of therapy should be made depending on the broncholith's size, mobility, location and local surgical expertise.

Hippuric acid as a significant regulator of supersaturation in calcium oxalate lithiasis: the physiological evidence.

At present, the clinical significance of existing physicochemical and biological evidence and especially the results we have obtained from our previous in vitro experiments have been analyzed, and we have come to the conclusion that hippuric acid (C6H5CONHCH2COOH) is a very active solvent of Calcium Oxalate (CaOX) in physiological solutions. Two types of experiments have been discussed: clinical laboratory analysis on the urine excretion of hippuric acid (HA) in patients with CaOX lithiasis and detailed measurements of the kinetics of the dissolution of CaOX calculi in artificial urine, containing various concentrations of HA. It turns out that the most probable value of the HA concentration in the control group is approximately ten times higher than the corresponding value in the group of the stone-formers. Our in vitro analytical measurements demonstrate even a possibility to dissolve CaOX stones in human urine, in which increased concentration of HA have been established. A conclusion can be that drowning out HA is a significant regulator of CaOX supersaturation and thus a regulation of CaOX stone formation in human urine. Discussions have arisen to use increased concentration of HA in urine both as a solubilizator of CaOX stones in the urinary tract and on the purpose of a prolonged metaphylactic treatment.

[Vitamin D and kidney diseases]. / Vitamine D et rein.

Calcitriol and analogs inhibit renin-angiotensin system, which has a pivotal role in glomerular and tubulo-interstitial damages and proteinuria, and inhibit NF-κB activation which is known to play an important role in renal diseases by promoting inflammation and fibrogenesis. Vitamin D presents interesting pleiotropic effects for the CKD patient (reduction of mortality, antiproteinuric effect and anti-inflammatory properties). "Native" vitamin D (cholecalciferol or ergocalciferol) administration in these patients also decrease parathyroid hormone levels. Native vitamin D administration in CKD patients is safe and does not lead to increased risk of vascular calcification, despite the known hypercalcemic and hyperphosphoremic properties of the molecule in its active form. Native vitamin D administration is not associated with an increased risk of renal stones, at pharmacological doses and without important concomitant administration of calcium salts. In the field of renal transplantation, experimental studies show that vitamin D analogs have a protective role against acute rejection but clinical studies remain mainly observational.

[Calculous pancreatitis].

Was shown current information on the diagnosis of pancreatic stones, their role in the development of calcificated (calculous) pancreatitis, as well as information on treatment of patients.

Epidermal growth factor receptor as a target for anti-proliferative treatment of proliferative cholangitis in hepatolithiasis.

BACKGROUND: In recent years, with a deeper understanding of pathologic changes in hepatolithiasis, more and more attention has been paid to the relationship of postoperative remnant proliferative cholangitis (PC) with stone recurrence and biliary restenosis, but effective management strategies have not yet been developed. Thus, the aim of this study was to determine whether epidermal growth factor receptor inhibitor (AG-1478) could inhibit hyperplasia and lithogenic potentiality of PC. METHODS: The PC animal model was established via retrograde insertion of a 5-0 nylon thread into the common bile duct through Vater's papilla. The common bile duct in the therapeutic group received a single intraluminal administration of AG-1478, followed by weekly intraperitoneal injections of AG-1478. Subsequently, influence of EGFR inhibitor on hyperplasia, apoptosis, and lithogenic potential of PC were evaluated via histology, expression changes of EGFR, BrdU, Ki-67, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Fas, mucin 5 AC, and collagen I. RESULTS: EGFR inhibitor AG-1478 was effective not only in inhibiting the mRNA and protein expression of EGFR, BrdU, and Ki-67, but also in increasing Fas mRNA expression and TUNEL-positive cells, as a result leading to the inhibition of hyperplasia of the biliary epithelium, submucosal gland, and collagen fibers in the diseased bile duct. Additionally, collagen I expression and fibrous thickness of the bile duct wall was significantly reduced, thereby reducing the incidence of biliary tract stricture secondary to PC. Also of note, treatment with AG-1478 could efficiently decrease the lithogenic potential of PC via inhibition of mucin 5AC expression and mucoglycoprotein secretion, hereby facilitating prevention of stone recurrence. CONCLUSION: EGFR antagonist AG-1478 had a potent anti-proliferative and anti-fibrotic effectiveness on PC and, therefore, holds promise as a candidate of PC treatment.

Long-term results of disodium etidronate treatment in pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease with alveolar microliths mainly composed of calcium phosphate. The gene responsible for the disease is SLC34A2, which encodes a type-IIb sodium phosphate cotransporter, has been described recently. Treatment of this disease is not clearly defined. Disodium etidronate is a member of bisphonates and it has been administered in these patients due to its inhibitory effect on the precipitation of hydroxyapatite microcrystals. Here, clinical and radiological improvement of two patients with PAM who were treated with disodium etidronate for 9 and 11 years, respectively, are presented. The pathogenetic mechanism of this treatment on the genetic basis of disease is discussed.

Enterolithiasis: An uncommon finding in abdominal tuberculosis.

Enterolithiasis, the formation of intestinal calculi due to stasis, is known to occur with abdominal tuberculosis. It has uncommonly been reported from India and only rarely in older children.

Broncholithiasis in a cat: clinical findings, long-term evolution and histopathological features.

A 14-year-old neutered male Persian cat was evaluated because of an acute exacerbation of a chronic cough of 2-3 years of duration. Physical examination was normal except for the auscultation of accentuated breath sounds and wheezes cranially on both sides of the chest. Complete blood count, biochemical parameters and urinalysis were normal. Thoracic radiographs showed a generalised nodular pattern with multiple mineral opacities. Oral prednisone and doxycycline were prescribed. Two weeks later, the frequency of the cough was significantly reduced. Terbutaline was recommended for relief of acute exacerbations. Three years later the cat was evaluated again due to a non-related disease that led to the euthanasia of the cat. Concerning its respiratory disease, the cat had experienced nearly asymptomatic periods of 3-6 weeks of duration punctuated by acute exacerbation periods of 7-10 days, during which terbutaline was useful to relieve the cough. Thoracic radiographs showed a mild increase in the size and extent of the pulmonary mineralisation. Histopathologically, mild bronchitis and bronchiectasis were evident, accompanied by calcified bronchial plugs and marked hyperplasia and hypertrophy of the seromucinous glands. Based on clinical and pathoanatomical findings, a final diagnosis of miliary broncholithiasis and bronchiectasis was made. Broncholithiasis should be considered in differential diagnosis of pulmonary mineralisation in cats. When no concomitant diseases are present, this rare disease appears to have a slowly progressive evolution that does not appear to carry a bad prognosis and may be satisfactorily managed with combinations of bronchodilators and corticosteroids.

Hepatolitiasis difusa: un desafío terapéutico / The difuse iintrahepathic lithiasis: detail the therapeutic

Antecedentes: La disminución de la morbilidad y mortalidad de la duodenopancreatectomía cefálica (DPC) en los últimos años permitió extender sus indicaciones a enfermedades benignas. Objetivos: Evaluar los resultados de la DPC en pacientes con enfermedades benignas en un centro de referencia de patología pancreática. Lugar de aplicación: Hospital público. Diseño: Retrospectivo. Población: Pacientes con diagnóstico anatomopatológico de enfermedad benigna (ausencia de carcinoma) en la pieza de resección de DPC. Método: Mediante un análisis retrospectivo de una base de datos prospectiva se evalúo la forma de presentación, el diagnóstico preoperatorio, la indicación quirúrgica, el tipo de cirugía y la morbilidad y mortalidad operatoria. Resultados: En el período 1993-2005 se realizaron 289 DPC, en 110 (38%) pacientes el diagnóstico histológico fue enfermedad benigna. La neoplasia quística (n=64) y la pancreatitis crónica (n=19) fueron las patologías más frecuentes (75,4%). Fueron sintomáticos 88 (81%) pacientes y asintomáticos los restantes. Las indicaciones quirúrgicas fueron el tratamiento de enfermedad benigna conocida (n=30) y la sospecha de malignidad (n=80). Se realizaron 74 DPC con preservación pilórica y 36 sin preservación pilórica. La morbilidad fue de 31,8% y la mortalidad de 0,9%. Conclusiones: Nuestra baja morbimortalidad justifica la DPC en el tratamiento de pacientes con enfermedades benignas en cabeza de páncreas y en pacientes con sospecha de malignidad.

A preliminary study of applying chemical biliary duct embolization to chemical hepatectomy in rats.

The high recurrence of hepatolithiasis, together with the high operative risk of hepatectomy for specially located stones, has not been settled effectively to date. Thus, this study was designed to investigate the feasibility of applying chemical biliary duct embolization (CBDE) to chemical hepatectomy in rats. As revealed in our results, the intrahepatic biliary ducts could be partially or completely occluded by both phenol and absolute ethanol. In addition, the embolization effect was greatly enhanced by further using cyanoacrylate. Also noteworthy is that CBDE resulted in massive death of hepatocytes, which were replaced by proliferated bile ductules and collagen. More importantly, the hepatocytes disappeared completely in the periphery of the embolized lobe where chemical hepatectomy was achieved. As for the comparison of embolic agents, the combination of phenol and cyanoacrylate exhibited even better fibrogenic effects than the combination of ethanol and cyanoacrylate. In conclusion, CBDE might be a promising approach for achieving the effects of chemical hepatectomy. The combination of phenol and cyanoacrylate potentially acted as a more effective agent for biliary duct embolization.

Hyperuricosuric calcium nephrolithiasis.

Since the findings of Yü and Gutman [1], the hyperuricosuric calcium stone former is a unique clinical entity. While an impressive number of clinical and epidemiologic studies implicate hyperuricosuria in calcium stone formation, the exact physicochemical mechanism by which uric acid affects calcium oxalate crystallization has not been proven. Allopurinol decreases stone recurrences and is the drug of choice for patients with isolated HCN.

Pulmonary alveolar microlithiasis in childhood: clinical and radiological follow-up.

This report describes a case of pulmonary alveolar microlithiasis that was diagnosed in an 8.5-year-old girl by high-resolution computed tomography (CT) and open lung biopsy. Presence of symptoms (productive cough, fever), their periodic occurrence (lasting up to 1 week), and comparatively long asymptomatic periods should be emphasized. Despite extensive X-ray abnormalities, tests of pulmonary interstitium involvement and exercise tests revealed normal results. A therapeutic regimen, including disodium etidronate, was administered for 18 months with no significant clinical or radiological improvement.

Pulmonary alveolar microlithiasis after Varicella zoster infection in a patient presenting with antiphospholipid syndrome and discoid lupus.

We present a case with diagnosis of pulmonary alveolar microlithiasis that illustrates the appearance of this rare chronic lung disease on conventional chest X-ray, high-resolution CT, and transbronchial lung biopsy. This is the first case reported which developed pulmonary alveolar microlithiasis after Varicella zoster infection in a patient with antiphospholipid antibodies and discoid lupus.