IS THERE A ROLE FOR BILIODIGESTIVE BYPASS SURGERY IN TREATING CHOLESTASIS IN ADVANCED PANCREATIC CANCER?

BACKGROUND: The unresectable pancreatic head tumors develop obstructive jaundice and cholestasis during follow-up. Cholestasis is associated with complications and treatment options are endoscopic stenting (ES) and biliary bypass surgery (BBS). AIMS: The aim of the current study was to compare the safety and efficacy of biliary bypass surgery (BBS) and endoscopic stenting (ES) for cholestasis in advanced pancreas cancer. METHODS: This is a retrospective cohort of patients with cholestasis and unresectable or metastatic pancreas cancer, treated with BBS or ES. Short and long-term outcomes were evaluated. We considered the need for hospital readmission due to biliary complications as treatment failure. RESULTS: A total of 93 patients (BBS=43; ES=50) were included in the study. BBS was associated with a higher demand for postoperative intensive care (37 vs.10%; p=0.002, p<0.050), longer intensive care unit stay (1.44 standard deviation±2.47 vs. 0.66±2.24 days; p=0.004, p<0.050), and longer length of hospital stay (7.95±2.99 vs. 4.29±5.50 days; p<0.001, p<0.050). BBS had a higher risk for procedure-related complications (23 vs. 8%; p=0.049, p<0.050). There was no difference in overall survival between BBS and ES (p=0.089, p>0.050). ES was independently associated with a higher risk for treatment failure than BBS on multivariate analysis (hazard ratio 3.97; p=0.009, p<0.050). CONCLUSIONS: BBS is associated with longer efficacy than ES for treating cholestasis in advanced pancreatic cancer. However, the BBS is associated with prolonged intensive care unit and hospital stays and higher demand for intensive care.

[Cholestasis, delirium and pulmonary nocardiosis in a man with systemic lupus erythematosus of late onset]. / Colestasis, delirium y nocardiosis pulmonar en un varón con lupus eritematoso sistémico de inicio tardío.

A case is presented of a 64-year-old male patient who was admitted because of delirium, jaundice, a pattern of cholestasis in the liver profile and a right lung mass in the context of a constitutional syndrome and weight loss in the last eight months. The lung mass was punctured and the culture of the obtained material developed white colonies, identified by mass spectrometry (MALDI-TOF) as Nocardia cyriacigeorgica. Regarding the clinical diagnosis, it was considered as systemic lupus erythematosus (SLE), on the basis of fulfilling 8 criteria according to SLICC 2012 group, and 24 points according to EULAR/ACR 2019. The liver biopsy showed a mixt cellular infiltrate in portal spaces, with absence of interphase hepatitis and presence of peripheral ductular reaction. These findings were interpreted as liver compromise relate to SLE. Delirium was also considered as a neurological manifestation related to SLE on the basis of ruling out other causes. After being treated with antibiotics and documenting a reduction in the size of the lung mass he received cyclophosphamide in intravenous pulses, achieving normalization of his liver profile and his state of consciousness, and a progressively weight recovering. A year after he was in good health. The report of this case is justified because of the rare presenting form of late onset SLE, as well as the concomitant pulmonary nocardiosis in the absence of previous immunosuppressant treatment.

Se presenta el caso de un varón de 64 años que fue internado por delirium asociado a ictericia con patrón de colestasis en el hepatograma, y una masa en el pulmón derecho en el contexto de pérdida de peso y síndrome constitucional de 8 meses de evolución. Se realizó punción de la masa pulmonar cuyo cultivo desarrolló colonias blanquecinas identificadas como Nocardia cyriacigeorgica por espectrometría de masas (MALDI-TOF MS). Se llegó al diagnóstico de lupus eritematosos sistémico (LES) por presentar 8 de los criterios de acuerdo con el grupo SLICC 2012 y 24 puntos de acuerdo a los criterios EULAR/ACR 2019. La biopsia hepática mostró leve y variable infiltrado inflamatorio mixto en espacios porta, con ausencia de hepatitis de interfase y presencia de reacción ductular periférica. Se interpretaron estos hallazgos como vinculados a hepatopatía por LES. El delirium fue interpretado como afectación neurológica por LES en base al descarte de otras enfermedades. Recibió tratamiento antibiótico y tras constatarse reducción del tamaño de la masa pulmonar se administraron pulsos de ciclofosfamida intravenosa. Evolucionó favorablemente, con normalización del hepatograma y el estado de conciencia, y recuperación del peso en forma progresiva. Al año se lo encontró en buen estado de salud. Justifica el reporte del caso la rara forma de presentación del LES de comienzo tardío, así como la nocardiosis pulmonar concomitante sin tratamiento inmunosupresor previo.

Dedicated cautery-enhanced tubular self-expandable metal stent for endoscopic ultrasound-guided hepaticogastrostomy: feasibility study.

BACKGROUND: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for biliary drainage in patients with obstructive pancreaticobiliary pathology when endoscopic retrograde cholangiopancreatography (ERCP) is not feasible. Despite its effectiveness, EUS-HGS is associated with a significant risk of adverse events. This study aimed to evaluate the feasibility and safety of a newly designed dedicated cautery-enhanced tubular self-expandable metal stent (SEMS) for EUS-HGS. METHODS: This multicenter prospective study included patients with malignant biliary obstruction in whom ERCP had failed because of tumor infiltration, inability to drain the intrahepatic ducts, or surgically altered anatomy. A dedicated cautery-enhanced tubular SEMS was used for EUS-HGS. Technical and clinical success rates, procedure times, and adverse events were evaluated. RESULTS: 20 patients underwent EUS-HGS with the dedicated stent. Technical and clinical success rates of 100% were achieved, with no reported severe adverse events or mortality. The median procedure time was 16 minutes. Recurrent biliary obstruction was observed in 1 patient. CONCLUSIONS: The dedicated cautery-enhanced tubular SEMS for EUS-HGS can simplify the procedure and enhance its safety and efficacy. This innovation shows promise for improving patient outcomes, although further studies are needed to validate these findings in a broader patient population.

Adjuvant Radiofrequency Ablation Along With Stenting Versus Stenting Alone for Biliary Tree Drainage in Patients With Malignant Biliary Strictures: A Systemic Review and Meta-analysis.

OBJECTIVE: This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer. METHODS: A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups. RESULTS: A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60-61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00-132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90-1.42). CONCLUSION: Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further.

A practical approach to the endoscopic management of biliary strictures after liver transplantation.

Biliary tract complications are an important cause of morbidity and mortality after liver transplantation (LT) occurring in 5% to 25% of patients. The most common biliary complication in LT recipients are strictures representing approximately half of these biliary adverse events. Bile duct strictures can be divided into anastomotic biliary strictures (ABS) and non-anastomotic biliary strictures (NABS) depending on their location in the biliary tree, being ABS the most encountered type. Several risk factors identified in previous studies can predispose to the development of ABS and NABS, especially those related to surgical techniques and donor characteristics. Magnetic resonance cholangiopancreatography (MRCP) is the recommended noninvasive imaging test for detecting post-LT biliary strictures, given its high sensitivity and specificity. Once the diagnosis of a biliary stricture after LT has been made, endoscopic retrograde cholangiopancreatography (ERCP) is the preferred initial therapy with good short and long-term results. Biliary sphincterotomy plus balloon dilation (BD) with placement of multiple plastic stents (MPS) has been the classic endoscopic approach for treating ABS, although fully-covered metallic stents (FCSEMS) have emerged as an alternative thanks to shorter total duration of stenting and fewer endoscopic procedures compared to MPS. In this review, we provide a practical update on the management of biliary strictures after LT, focusing our attention on the available evidence in the endoscopic therapy.

Clinical practice guideline on the use of single-operator cholangioscopy in the diagnosis of indeterminate biliary stricture and the treatment of difficult biliary stones.

BACKGROUND AND AIMS: Single-operator cholangioscopy (SOC) offer a diagnostic and therapeutic alternative with an improved optical resolution over conventional techniques; however, there are no standardized clinical practice guidelines for this technology. This evidence-based guideline from the Colombian Association of Digestive Endoscopy (ACED) intends to support patients, clinicians, and others in decisions about using in adults the SOC compared to endoscopic retrograde cholangiopancreatography (ERCP), to diagnose indeterminate biliary stricture and to manage difficult biliary stones. METHODS: ACED created a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. Universidad de los Andes and the Colombia Grading of Recommendations Assessment, Development and Evaluation (GRADE) Network supported the guideline-development process, updating and performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The GRADE approach was used, including GRADE Evidence-to-Decision frameworks. RESULTS: The panel agreed on one recommendation for adult patients with indeterminate biliary strictures and one for adult patients with difficult biliary stones when comparing SOC versus ERCP. CONCLUSION: For adult patients with indeterminate biliary strictures, the panel made a conditional recommendation for SOC with stricture pattern characterization over ERCP with brushing and/or biopsy for sensitivity, specificity, and procedure success rate outcomes. For the adult patients with difficult biliary stones the panel made conditional recommendation for SOC over ERCP with large-balloon dilation of papilla. Additional research is required on economic estimations of SOC and knowledge translation evaluations to implement SOC intervention in local contexts.

Síndrome colestásico como forma de presentación de linfoma no Hodgkin. Reporte de un caso pediátrico / Cholestatic syndrome as a presentation of non-Hodgkin lymphoma. A pediatric case report

La ictericia colestásica se debe a la alteración de la secreción de bilirrubina conjugada; es una de las posibles causas la alteración del flujo biliar por obstrucción de la vía biliar extrahepática. El linfoma es la tercera neoplasia más frecuente en pediatría, mientras que los tumores pancreáticos son poco frecuentes y, en su mayoría, lesiones benignas. Las manifestaciones clínicas de los tumores de localización retroperitoneal son poco específicas y suelen ser tardías, por lo que la sospecha clínica debe ser alta. El objetivo del siguiente trabajo es presentar el caso de un niño de 7 años con síndrome colestásico en el que se halló un tumor en la cabeza del páncreas que comprimía la vía biliar extrahepática. El diagnóstico del tumor fue linfoma no Hodgkin (LNH). Se destaca la infrecuencia de este tumor en esta localización en la edad pediátrica

Cholestatic jaundice is due to an alteration in conjugated bilirubin secretion; a possible cause is an altered bile flow resulting from an obstruction of the extrahepatic bile duct. A lymphoma is the third most common neoplasm in pediatrics, while pancreatic tumors are rare and mostly benign. The clinical manifestations of retroperitoneal tumors are not very specific and are usually late, so a high level of clinical suspicion is required. The objective of this study is to describe the case of a 7-year-old boy with cholestatic syndrome with a tumor in the head of the pancreas compressing the extrahepatic bile duct. The tumor diagnosis was non-Hodgkin lymphoma (NHL). It is worth noting that the presence of a tumor in this location in pediatric age is uncommon

Factors associated with cholestasis in newborns with gastroschisis.

OBJECTIVE: To describe the incidence and to analyze risk factors associated with cholestasis in neonates with gastroschisis. METHODS: This is a retrospective cohort study in a tertiary single center analyzing 181 newborns with gastroschisis between 2009 and 2020. The following risk factors associated with cholestasis were analyzed: gestational age, birth weight, type of gastroschisis, silo closure or immediate closure, days of parenteral nutrition, type of lipid emulsion, days of fasting, days to reach a full diet, days with central venous catheter, presence of infections, and outcomes. RESULTS: Among the 176 patients evaluated, 41 (23.3%) evolved with cholestasis. In the univariate analysis, low birth weight (p=0.023), prematurity (p<0.001), lipid emulsion with medium-chain triglycerides and long-chain triglycerides (p=0.001) and death (p<0.001) were associated with cholestasis. In the multivariate analysis, patients who received lipid emulsion with fish oil instead of medium chain triglycerides/long chain triglycerides (MCT/LCT) emulsion had a lower risk of cholestasis. CONCLUSIONS: Our study shows that lipid emulsion with fish oil is associated with a lower risk of cholestasis in neonates with gastroschisis. However, this is a retrospective study and a prospective study should be performed to confirm the results.

Cholestatic syndrome as a presentation of non-Hodgkin lymphoma. A pediatric case report. / Síndrome colestásico como forma de presentación de linfoma no Hodgkin. Reporte de un caso pediátrico.

Cholestatic jaundice is due to an alteration in conjugated bilirubin secretion; a possible cause is an al- tered bile flow resulting from an obstruction of the extrahepatic bile duct. A lymphoma is the third most common neoplasm in pediatrics, while pancreatic tumors are rare and mostly benign. The clinical mani- festations of retroperitoneal tumors are not very specific and are usually late, so a high level of clinical suspicion is required. The objective of this study is to describe the case of a 7-year-old boy with cholestatic syndrome with a tumor in the head of the pancreas compressing the extrahepatic bile duct. The tumor diagnosis was non-Hodgkin lymphoma (NHL). It is worth noting that the presence of a tumor in this location in pedia- tric age is uncommon.

La ictericia colestásica se debe a la alteración de la secreción de bilirrubina conjugada; es una de las posibles causas la alteración del flujo biliar por obstrucción de la vía biliar extrahepática. El linfoma es la tercera neoplasia más frecuente en pediatría, mientras que los tumores pancreáticos son poco frecuentes y, en su mayoría, lesiones benignas. Las manifestaciones clínicas de los tumores de localización retroperitoneal son poco específicas y suelen ser tardías, por lo que la sospecha clínica debe ser alta. El objetivo del siguiente trabajo es presentar el caso de un niño de 7 años con síndrome colestásico en el que se halló un tumor en la cabeza del páncreas que comprimía la vía biliar extrahepática. El diagnóstico del tumor fue linfoma no Hodgkin (LNH). Se destaca la infrecuencia de este tumor en esta localización en la edad pediátrica.

A Retrospective Multicentric Study of 34 Patients with Niemann-Pick Type C Disease and Early Liver Involvement in France.

OBJECTIVE: To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder. STUDY DESIGN: Patients with genetically confirmed NP-C (NPC1, n = 31; NPC2, n = 3) and liver involvement before age 6 months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining. RESULTS: At initial evaluation (median age, 17 days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68+ storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6 months of life, including 3 from liver involvement. In patients who survived beyond age 6 months (median follow-up, 6.1 years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients. CONCLUSIONS: Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.

Síndrome de Alagille, reporte de un caso y revisión de la literatura / Alagille Syndrome, case study and literature review / Sindrome de Alagille, relato de caso e revisão de literatura

El síndrome de Alagille es una patología poco frecuente, de herencia autosómica dominante. Se caracteriza por la presencia de colestasis crónica progresiva ocasionada por hipoplasia de las vías biliares; anomalías vertebrales, oculares y cardíacas, y fenotipo facial particular. Entre sus diagnósticos diferenciales se incluyen las infecciones, enfermedades endocrinometabólicas, atresia biliar y causas idiopáticas. El pronóstico de este síndrome es variable y depende de la entidad de la afectación hepática y los defectos cardiovasculares. El abordaje terapéutico suele ser interdisciplinario e individualizado, enfocado en el control sintomático, prevención de la malnutrición y el déficit de vitaminas liposolubles. Se presenta el caso de un lactante de 2 meses en el que se estudiaron las causas más frecuentes de colestasis y se llegó al diagnóstico de síndrome de Alagille. Se describe su abordaje terapéutico y seguimiento.

Alagille syndrome is an inherited autosomal dominant rare disease. It is characterized by the presence of progressive chronic cholestasis caused by hypoplasia of the bile ducts; vertebral, ocular and cardiac anomalies, and particular facial phenotype. Its differential diagnoses include infections, endocrine-metabolic diseases, biliary atresia and idiopathic causes. The prognosis of this syndrome is variable and depends on the degree of liver involvement and cardiovascular defects. The therapeutic approach is usually interdisciplinary and customized, focused on symptomatic control, prevention of malnutrition and fat-soluble vitamin deficiency. We present the case of a 2-month-old infant in whom the most frequent causes of cholestasis were studied and to whom Alagille Syndrome was diagnosed. We hereby describe its therapeutic approach and follow-up.

A síndrome de Alagille é uma doença rara, hereditária, autossômica e dominante. Caracteriza-se pela presença de colestase crônica progressiva causada por hipoplasia das vias biliares; anomalias vertebrais, oculares e cardíacas e fenótipo facial particular. Seus diagnósticos diferenciais incluem infecções, doenças endócrino-metabólicas, atresia biliar e causas idiopáticas. O prognóstico desta síndrome é variável e depende do grau de envolvimento hepático e defeitos cardiovasculares. A abordagem terapêutica geralmente é interdisciplinar e personalizada, focada no controle sintomático, prevenção da desnutrição e deficiência de vitaminas lipossolúveis. Apresentamos o caso de uma criança de 2 meses de idade em que foram estudadas as causas mais frequentes de colestase e a quem foi diagnosticada Síndrome de Alagille. Descrevemos a sua abordagem terapêutica e seguimento.

A single session of EUS directed transgastric ERCP and EUS FNB in a patient with RYGB, pancreatic head tumor and biliary obstruction.

The alteration of the gastrointestinal anatomy represents a challenge for the performance of endoscopic procedures in case of bile duct obstruction. Follow we present the technique used in a patient with altered anatomy and a mass in the head of the pancreas with obstruction of the bile duct through endoscopic ultrasound-guided trans gastric retrograde cholangiopancreatography.

Clinical value of preferred endoscopic ultrasound-guided antegrade surgery in the treatment of extrahepatic bile duct malignant obstruction.

OBJECTIVES: To explore the clinical value of preferred ultrasound endoscopic guided biliary drainage in patients with extrahepatic biliary obstruction with intrahepatic biliary ectasis. METHODS: A total of 58 patients with malignant obstruction and intrahepatic bile duct expansion, including 32 males, 26 females and median age 65 (58‒81) were selected. A prospective randomized controlled study was randomized into EUS-AG and ERCP-BD, with 28 patients in EUS-AG and 30 in ERCP-BD. The efficacy of the two treatments, operation success rate, operation time, the incidence of complications, hospitalization days, cost, unimpeded stent duration, and survival time were compared. RESULTS: 1) The surgical success rate in group EUS-AG was 100%, and in group, ERCP-BD was 96.67%. There was no statistical difference in surgical success rate in the two groups (p>0.05). 2) Average operating time in EUS-AG was (23.69±11.57) min, and in ERCP-BD was (36.75±17.69) min. The difference between the two groups has statistical significance (p<0.05). 3) The clinical symptoms of successful patients were significantly relieved. Compared with the preoperative procedure, the differences in group levels had statistical significance (p<0.05); TBIL, ALP, WBC and CRP levels, no statistical significance difference in groups (p>0.05). CONCLUSION: EUS-AG operation has short time, low incidence of complications, safe, effective, and can be used as the preferred treatment plan for patients with extrahepatic biliary duct malignant obstruction associated with intrahepatic biliary duct expansion; EUS-AG operation has more unique clinical advantages for patients with altered gastrointestinal anatomy or upper gastrointestinal obstruction.