Clinical Outcomes of EUS-Guided Choledochoduodenostomy for Biliary Drainage in Unresectable Pancreatic Cancer: A Case Series.

Introduction. Pancreatic ductal adenocarcinoma (PDA) is associated with poor prognosis and 98% loss-of-life expectancy. 80% of patients with PDA are unfit for radical surgery. In those cases, emphasis is set on management of cancer-related symptoms, among which obstructive jaundice is most common. Endoscopic ultrasound-guided biliary drainage (EUS-BD) emerges as a valid alternative to the well-accepted methods for treatment of biliary obstruction. Patient Selection. Five consecutive patients with unresectable pancreatic malignancy, were subjected to EUS-BD, particularly EUS-guided choledochoduodenostomy (EUS-CDS). Ethics. Oral and written informed consent was obtained in all cases prior procedure. Technique. EUS-guided puncture of the common bile duct was performed, followed by advancement of a guidewire to the intrahepatic bile ducts. After dilation of the fistulous tract with a cystotome, a fully covered self-expandable metal stent was inserted below the hepatic confluence and extending at least 3 cm in the duodenum. Technical and clinical success was achieved in four patients without adverse events. In one patient procedure failed due to dislocation of the guidewire, with consequent biliary leakage requiring urgent surgery. Recovery was uneventful with no further clinical sequelae and there was no mortality associated with procedure. Discussion. Introduced in 2001, EUS-guided biliary drainage has become an accepted option for treatment of obstructive jaundice. According to recent guidelines published by European Society of Gastrointestinal Endoscopy (ESGE) in 2022, EUS-CDS is a preferred modality to percutaneous transhepatic biliary drainage (PTBD) and surgery in patients with failed ERCP, with comparable efficiency and better safety profile, which is supported by our experience with the procedure. Conclusions. Our case series suggests that EUS-CDS is an excellent option for palliative management of malignant distal biliary obstruction, emphasizes on the importance of adequate technique and experience for the technical success, and urges the need for future research on establishing the best choice for guidewire and dilation device.

Unique case of abdominal aortic aneurysm causing obstructive jaundice and duodenal obstruction.

Obstruction of the duodenum by an abdominal aortic aneurysm (AAA) (aortoduodenal syndrome) has rarely been reported. It presents with symptoms of upper gastrointestinal (GI) tract obstruction. Obstructive jaundice caused by an AAA is also extremely rare and requires high clinical suspicion. We present a unique case with informed consent of an elderly gentleman who presented with both rare presentations over a course of few months. After extensive literature search, we have found case reports of patients showing either of the two unusual presentations, but none were found to show them together.

Lockdown period during SARS COVID-19 endemic outbreak in Taiwan did not cause an increase of the complications nor mortality of patients received endoscopic retrograde cholangiopancreatography: A single-center retrospective study.

BACKGROUND: Coronavirus disease 2019, known as a widespread, aerosol spreading disease, has affected >549 000 000 people since 2019. During the lockdown period, dramatic reduction of elective endoscopic procedures, including endoscopic retrograde cholangiopancreatography, had been reported worldwide, leading to delayed diagnosis and treatment. Nevertheless, whether patients' hospital stays and complication rate of endoscopic retrograde cholangiopancreatography (ERCP) during the lockdown period were influenced by the pandemic still remains controversial. METHODS: Patients who diagnosed with obstructive jaundice and acute cholangitis in the lockdown period, May 16 to July 26, 2021, were compared to the same prepandemic period in 2019. RESULTS: A total of 204 patients in 2019 and 168 patients in 2021 were diagnosed with acute biliary cholangitis or obstructive jaundice, and 82 of the patients in 2019 and 77 patients in 2021 underwent ERCP ( p = 0.274). Patients whose quick Sequential Organ Failure Assessment (qSOFA) score was ≥ 2 occurred more during the lockdown period than during the normal period (24/77, 31.1% vs 12/82, 14.6%; p = 0.013). The initial laboratory data, including, total bilirubin (4.12 in 2021 vs 3.08 mg/dL in 2019; p = 0.014), gamma-glutamyl transferase (378 in 2021 vs 261 U/L in 2019; p = 0.009), and alkaline phosphatase (254 in 2021 vs 174 U/L in 2019; p = 0.002) were higher during the lockdown period compared to 2019. Hospital stay was statistically significant longer in the lockdown period (11 days [7.00-22.00] in 2021 vs 8 days in 2019 [6.00-12.00]; p value = 0.02). Multivariate analysis showed that qSOFA ≥ 2 (hazard ratio [HR] = 3.837, 95% confidence interval [CI] = 1.471-10.003; p = 0.006), and malignant etiology (HR = 2.932, 95% CI = 1.271-6.765; p = 0.012) were the statistically significant factors for a prolonged hospital stay, which was defined as hospital stay >21 days. ERCP-related complications and mortality rate were not statistically different between the two periods. CONCLUSION: Patients from May 16 to July 26, 2021, the lockdown period, had longer hospital stays and higher biliary tract enzyme levels, which indicated more severe disease. Nevertheless, ERCP could be safely and successfully performed even during the medical level 3 alert lockdown period without causing an increase in procedure-related complications and mortality.

A novel pathogenesis concept of biliary atresia approached by combined molecular strategies.

Cholestatic jaundice is one of the most common neonatal conditions. BA, a correctable cholangiopathy, presents with cholestatic jaundice within the first weeks of life. The inflammation of bile ducts leads to progressive fibrosclerosis involving biliary trees, followed by cirrhosis and liver failure. With the use of modern molecular studies, this research aimed to define a novel pathogenesis by exploring variations. We performed genetic discovery by using supervised and unsupervised approaches. Ultimately, a combination of genetic variations and survival data was analyzed to strengthen the novel concept in this study. In this study, coding regions were explored to identify rare deleterious variants within genes from the first analysis together with gene sets reported in PFIC, and diseases with hyperbilirubinemia. Our unsupervised prioritization was primarily designed to identify novel causal genes from nonsynonymous variants derived by three biostatistical algorithms: enrichment analysis, burden test, and trio study. Survival analysis was integratively evaluated with a combination of identified causal genes. The individuals with identified variants from the supervised approach were frequently related to the severity of cirrhosis and poor postoperative outcome. In the unsupervised approach, nonsynonymous variants were enriched. Cilium and muscle related pathways had a significant correlation. CCDC8 was statistically significant gene in which six cases carried mutations identified through burden analysis. Individuals who carried variants in corresponding genes and significant pathways had significantly lower native-liver survival than individuals in whom none of these variants were identified (log-rank p value 0.016). This study explored genetic variations by multiple strategies. Different pathways of cholestatic diseases have been found to be associated with BA. Therefore, BA may be characterized as a shared sequela of many cholestatic disorders. Susceptibility in those pathways suggested an association with BA and strengthened this proposed novel hypothesis. The results emphasized the consequences of many disruptive pathophysiologies.

The Protective Effect of Sulodexide on Acute Lung Injury Induced by a Murine Model of Obstructive Jaundice.

Introduction: The effect of sulodexide (SLX) on obstructive jaundice- (OJ-) induced acute lung injury (ALI) in rats was examined in this study. Methods: In this study, 48 rats were randomly assigned to one of six groups: sham, OJ, OJ+saline, OJ+SLX (0.5 mg/ml/d), OJ+SLX (1 mg/ml/d), and OJ+SLX (2 mg/ml/d). The pathological lung injury was assessed by histological analysis and lung injury grading. ELISA kits were used to evaluate the expression of IL-6, IL-1, TNF-α, and syndecan-1 (SDC-1) in bronchoalveolar lavage fluids (BALFs). Commercial assay kits were performed to evaluate malondialdehyde (MDA) production and catalase (CAT) activity in lung tissues. The apoptosis was assessed by TUNEL assay. The lung microvascular permeability was investigated using Evans blue leakage, lung wet/dry weight (W/D) ratio, and lung permeability index (LPI). SDC-1, claudin-5, ZO-1, and VE cadherin expression levels in lung tissues were measured using Western blot. Results: The OJ-induced ALI rats showed severe lung injury. The value of IL-6, IL-1ß, TNF-α, and SDC-1 in BALFs was remarkedly increased in the OJ group. MDA content, apoptotic area, apoptotic molecules, and SDC-1 level were all higher in the OJ group's lung tissues than in the sham group. CAT activity, Evans blue leakage, W/D ratio, LPI, and expression of claudin-5, ZO-1, and VE cadherin were all lower in the OJ group compared to the sham group. The degenerative alterations in lung tissue improved after 7 days of treatment with 2 mg/ml SLX. The BALFs had lower amounts of IL-6, IL-1, TNF-α, and SDC-1. The SLX therapy reduced MDA levels while restoring CAT activity. In lung tissues, SLX reduced apoptotic area and SDC-1 expression. SLX reduced lung microvascular permeability by raising the expression of Claudin-5, ZO-1, and VE-cadherin in lung tissue when compared to the OJ group. Conclusion: The results suggested that SLX attenuates OJ-induced ALI in rats by protecting the pulmonary microvascular endothelial barrier.

Concomitant methimazole-induced agranulocytosis and cholestatic jaundice in a young woman.

A woman in her 30s presented to the emergency department with new-onset sore throat and fever. She had recently been diagnosed with Graves' disease 3 months prior. As a result, she was initiated on atenolol and methimazole for management. Her methimazole dosing had been stable at 15 mg daily for the month prior to presentation. Investigation revealed severe neutropenia and jaundice. She was found to have concomitant agranulocytosis and cholestatic jaundice secondary to methimazole.Methimazole was discontinued on admission and the patient received granulocyte colony-stimulating factor for an absolute neutrophil count (ANC) of zero. She was placed on broad-spectrum antibiotics and intravenous steroids for epiglottic and supraglottic oedema noted on bedside laryngoscopy. ANC and bilirubin improved over a 2-week hospital course. She was discharged on a temporary regimen of propranolol, dexamethasone and potassium iodide until she was able to undergo successful thyroidectomy for definitive management of Graves' disease outpatient.

[SURGICAL PALLIATION FOR PANCREATIC CANCER].

INTRODUCTION: Pancreatic cancer (PC) is the 11th most common malignancy worldwide, however, entailing a mortality in excess of 90% within 5 years from diagnosis, it is the 4th most fatal malignant disease. PC is commonly diagnosed at an advanced stage, in which curative resection is no longer possible. Even patients who present with potentially curable disease will have upward of 30% recurrence of their disease within the first year. Thus, palliative therapy has paramount importance in patient management. The purpose of palliative care in these patients is to relieve symptoms and improve quality of life. This article reviews the current state of invasive palliation techniques for advanced PC, which are commonly directed towards three main symptoms: gastric/duodenal obstruction, obstructive jaundice, and epigastric pain. We describe the pros and cons of the different techniques, along with current front-line technology advancements. Endoscopic stenting is highly efficient in patients with gastric/duodenal obstruction or obstructive jaundice, with a generally low complication rate, short hospitalization and sustained quality of life. Bypass surgery should be considered in patients with a long-anticipated life expectancy, following higher rates of long-term stent failure, or when endoscopic stent procedure is not possible or has failed. When treating abdominal pain, celiac plexus neurolysis is considered as the first-line treatment. Pancreatic cancer is a complex and commonly lethal disease strongly affecting patient quality of life. It is important to consider the specific patient's personal characteristics and disease status when planning their palliative care.

Effects of preoperative biliary drainage methods and time to postoperative complications after biliary drainage in periampullary tumors.

OBJECTIVE: To compare postoperative morbidity and mortality results in patients with and without endoscopic and percutaneous transhepatic biliary drainage due to obstructive jaundice caused by a periampullary tumor and to examine the effect of intervals until surgery on postoperative morbidity and mortality in patients who underwent preoperative biliary drainage (BD). METHODS: Patients were divided into 3 groups according to their BD status. Group1, no biliary drainage (NBD), Group2, Endoscopic biliary drainage (EBD), Group3, Percutaneous transhepatic biliary drainage (PBD). Patients who underwent biliary drainage before pancreaticoduodenectomy (PD) were divided into 3 intervals according to the time interval between drainage and surgery: Short interval; patients undergoing surgery in 21 days and <, Medium interval; between 22-42 days, Long interval; 43 days and >. Groups and intervals were compared in terms of postoperative morbidity and mortality. RESULTS: Of the 122 patients who underwent PD, 76 (62.3%) were male, and 46 (37.7%) were female. Within these patients, 47 (38.52%) had NPD, 42 (34.42%) had EBD, and 33 (27.05%) had PBD. The rate of postoperative Grade B and C fistula was higher in the groups that underwent preoperative drainage compared to the group without preoperative drainage (p = 0.007). CONCLUSION: It was determined that the postoperative complication rate was lower in patients who did not undergo BD compared to patients who underwent biliary drainage. Besides, the endoscopic drainage method was observed to be associated with fewer complications than the percutaneous transhepatic drainage method. KEY WORDS: Preoperative biliary drainage, Pancreaticoduodenectomy, Periampullary tumors, Post procedure complication, Timing.

Imaging in Pediatric Obstructive Jaundice.

Cholestatic jaundice characterized by elevated conjugated bilirubin can be due to multitude of factors in neonates and childhood. Extrahepatic biliary atresia (EHBA), choledochal cyst, neonatal hepatitis, cytomegalovirus (CMV), and biliary plug are some of the common causes in neonate and early infancy. Causes in late infancy and childhood comprises viral hepatitis, choledochal cyst, cholelithiasis, worm infestation, and biliary compression secondary to extrinsic causes (node, collection, tumor). Some serious disorders like biliary atresia must be considered with the emphasis on early diagnosis of treatable causes. In the modern era, with multiple diagnostic modalities available including high-resolution ultrasonography, magnetic resonance imaging (MRI), CT scan, and nuclear imaging [hepatobiliary iminodiacetic acid (HIDA) scan], rapid diagnosis can be made in many surgically treatable cases. The authors will discuss the imaging modality available with advantages, disadvantages, and common indications of each modality, and overview of obstructive jaundice discussing the wide spectrum of causes in neonates and late childhood. Combining available knowledge with careful and meticulous search can help narrow down the diagnosis and initiate prompt treatment.

Transarterial chemoembolization for hepatocellular carcinoma with vascular invasion.

Although the global guidelines only recommend systemic therapy for hepatocellular carcinoma with vascular invasion, various treatments are performed for it. Among them, transarterial chemoembolization (TACE) is the most frequent option; however, standard techniques have not been established. Conventional TACE (cTACE) has also been frequently performed for tumors invading the portal vein (PVTT), hepatic vein (HVTT), and bile duct (BDTT). In cTACE for PVTT, selective catheterization into the tumor-feeder is essential to avoid adverse effects. However, if it is unsuccessful, injection of embolic agents under balloon occlusion of the hepatic artery can improve the therapeutic effects and avoid hepatic infarction. When marked arterioportal shunts are demonstrated, embolization with gelatin sponge particles soaked with a chemotherapeutic solution is another option. Arteriovenous shunts accompanied by HVTT may cause systemic embolization due to migration of embolic agents, and occlusion of a shunt-draining hepatic vein using a balloon catheter can reduce the risk. BDTT is often accompanied by obstructive jaundice; therefore, endoscopic or percutaneous biliary drainage is required when the serum total bilirubin concentration is ≥3 mg dl-1. TACE should be performed as selectively as possible and attention should also be paid to the risk of obstructive jaundice and/or pancreatitis caused by sloughing of necrotized BDTT.

Towards standardization of management of gallbladder carcinoma with obstructive jaundice: Analysis of 113 cases over 10 years at a single institution.

BACKGROUND: Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways. METHODS: Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS). RESULTS: Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%. CONCLUSION: Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.

The pathogenesis of renal injury in obstructive jaundice: A review of underlying mechanisms, inducible agents and therapeutic strategies.

Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfunctions caused by OJ-induced kidney injury as OJKI. However, the etiology of OJKI is still not fully clear, and research studies on how OJKI becomes a facilitated factor of OJ are limited. This article reviews the underlying pathological mechanism from five aspects, including metabolisms of bile acids, hemodynamic disturbances, oxidative stress, inflammation and the organic transporter system. Some nephrotoxic drugs and measures that can enhance or reduce the renal function with potential intervention in perioperative periods to alleviate the incidence of OJKI were also described. Furthermore, a more in-depth study on the pathogenesis of OJKI from multiple aspects for exploring more targeted treatment measures were further put forward, which may provide new methods for the prevention and treatment of clinical OJKI and improve the prognosis.

Guía de práctica clínica en atresia de las vías biliares / Clinical practice guidelines in biliary atresia

Basada en la mejor evidencia científica disponible, se presenta la guía de práctica clínica en atresia de vías biliares, la cual se define como una obstrucción progresiva de las vías biliares intra- o extrahepáticas en recién nacidos y lactantes pequeños y causa ictericia colestásica grave y cirrosis hepática. Es una enfermedad poco frecuente, de etiología desconocida, con mayor incidencia en países asiáticos. Clínicamente se expresa por ictericia obstructiva, acolia, coluria y hepatoesplenomegalia. Los complementarios expresan una hiperbilirrubinemia directa con aumento de las enzimas hepáticas, y el diagnóstico se confirma en nuestro hospital con la colangiografía, generalmente en el curso de una laparoscopía. El tratamiento es quirúrgico y consiste en la portoenterostomía de Kasai, con mejores resultados en cuanto al drenaje biliar si se realiza antes de los 60 días de vida, así como el trasplante hepático. La enfermedad tiene un curso progresivo hacia la cirrosis hepática en etapas tempranas de la vida, sobre todo si no se realiza el diagnóstico y tratamiento quirúrgico precozmente, con implicaciones en la supervivencia y calidad de vida de estos pacientes. Por tanto, referir precozmente al paciente con sospecha de atresia de vías biliares a un centro especializado es la piedra angular de la actitud médica. La presente guía de práctica clínica pretende ofrecer las herramientas técnicas estandarizadas para mejorar los resultados a los pacientes con esta enfermedad, así como contribuir con la docencia y las investigaciones(AU)

Based on the best scientific evidence available, it is presented the clinical practice guidelines on biliary atresia. This disease is defined as a progressive obstruction of the intra and/or extrahepatic bile ducts in newborns and young infants, causing severe cholestatic jaundice and cirrhosis of the liver. It is a rare disease of unknown etiology, with a higher incidence in Asian countries. It is clinically expressed by obstructive jaundice, acholia, choluria and hepatosplenomegaly. Laboratory tests show a direct hyperbilirubin and elevated liver enzymes, and in our hospital, the diagnosis is confirmed by a cholangiography, usually during a laparoscopy procedure. It has surgical treatment and it involves a Kasai portoenterostomy, with better results regarding biliary drainage if it is performed before 60 days of life, as well as liver transplant. This condition has a progressive course towards liver cirrhosis in early stages of life, mainly if the diagnosis and surgical treatment are not made timely, with implications for the survival and quality of life of these patients. Therefore, early referral of the patient with suspected biliary atresia to a specialized center is the cornerstone of the medical attitude. This clinical practice guidelines aims to offer standardized technical tools to improve the outcome for patients with this disease, as well as to contribute to teaching and research(AU)

An electron microscopy study of liver and kidney damage in an experimental model of obstructive jaundice.

With this experimental study we investigated the consequences of ligation of the common bile duct (CBD) on hepatic cells and on the renal ultrastructure by electron microscopy and also determine the effects after liberation of the ductus joint in order to clarify the mechanisms of renal failure commonly observed in cholestatic liver disease. The study was conducted on 53 Wistar albino rats divided into 4 subgroups. In the comparison group (sham) we proceeded to the simple laparotomy. After preparation of the common bile duct of all the rats of the four groups, and ligation of the duct at the level of the distal third, eight rats in each group were sacrificed on the 3rd, 7th, 10th and 14th day after surgery, taking blood samples to measure the serum levels of ALP and bilirubin, and liver and renal tissue samples for histological evaluation. In four rats of each group the common bile duct was unligated at the same deadlines to obtain free drainage of the bile for a week. At the end of this week, the rats were sacrificed by collecting blood and liver and kidney tissue samples. RESULTS: after CBD ligation in both groups, the ALP value, total and direct bilurubin levels were proportionally increased. After duct release, bilurubin levels decreased significantly. In group II, while large lipid granules were observed to indicate oxidative damage, mitochondrial swelling and crystals were observed after duct liberation. Areas of glycogen and normal mitochondria were observed in group IV. After duct release in this group, increases in Ito granules, lipid granules and normal mitochondria were observed, which may reflect the evolution of hepatic regeneration. When renal tissue was examined in group II, fusion processes in the feet, thickening of the basement membrane and mesengium were observed, and mitochondrial crystals were observed in renal tissue as well as in the liver after duct release. Damage in group III and group IV was increased parallel to prolongation of jaundice and after loosening persistent damage with mitochondrial crystals. CONCLUSION: Ultrastructural changes in rat liver tissue in conditions of obstructive jaundice may be reversible after restoration of drainage. On the other hand, ultrastructural changes in renal tissue in cases of prolonged jaundice are irreversible even if the internal drainage is restored. KEY WORDS: Bile Duct, Liver, Kidney, Obstructive Jaundice.

Yinchenhao decoction attenuates obstructive jaundice-induced liver injury and hepatocyte apoptosis by suppressing protein kinase RNA-like endoplasmic reticulum kinase-induced pathway.

BACKGROUND: Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes, and leads to apoptosis. Apoptosis is very important in regulating the homeostasis of the hepatobiliary system. Endoplasmic reticulum (ER) stress is one of the signaling pathways that induce apoptosis. Moreover, the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-induced apoptotic pathway is the main way; but its role in liver injury remains unclear. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that alleviates liver injury and apoptosis, yet its mechanism is unknown. We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice (OJ). AIM: To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein (CHOP)-growth arrest and DNA damage-inducible protein 34 (GADD34) pathway and B cell lymphoma/leukemia-2 related X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) ratio. METHODS: For in vivo experiments, 30 rats were divided into three groups: control group, OJ model group, and YCHD-treated group. Blood was collected to detect the indicators of liver function, and liver tissues were used for histological analysis. For in vitro experiments, 30 rats were divided into three groups: G1, G2, and G3. The rats in group G1 had their bile duct exposed without ligation, the rats in group G2 underwent total bile duct ligation, and the rats in group G3 were given a gavage of YCHD. According to the serum pharmacology, serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells. Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) assay was used to detect BRL-3A hepatocyte apoptosis. Alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in the medium were detected. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to detect protein and gene expression levels of PERK, CHOP, GADD34, Bax, and Bcl-2 in the liver tissues and BRL-3A cells. RESULTS: Biochemical assays and haematoxylin and eosin staining suggested severe liver function injury and liver tissue structure damage in the OJ model group. The TUNEL assay showed that massive BRL-3A rat hepatocyte apoptosis was induced by OJ. Elevated ALT and AST levels in the medium also demonstrated that hepatocytes could be destroyed by OJ. Western blot or qRT-PCR analyses showed that the protein and mRNA expression levels of PERK, CHOP, and GADD34 were significantly increased both in the rat liver tissue and BRL-3A rat hepatocytes by OJ. The Bax and Bcl-2 levels were increased, and the Bax/Bcl-2 ratio was also increased. When YCHD was used, the PERK, CHOP, GADD34, and Bax levels quickly decreased, while the Bcl-2 levels increased, and the Bax/Bcl-2 ratio decreased. CONCLUSION: OJ-induced liver injury and hepatocyte apoptosis are associated with the activation of the PERK-CHOP-GADD34 pathway and increased Bax/Bcl-2 ratio. YCHD can attenuate these changes.

Dexmedetomidine Attenuates Lung Injury in Obstructive Jaundice Rats Through PI3K/Akt/HIF-1α Signaling Pathway.

BACKGROUND: Obstructive jaundice (OJ) could seriously affect the biochemical and immune functions in the body. Up to now, there are still poor evidences about the role of dexmedetomidine in OJ. METHODS: Male Wistar rats were divided into four groups: Sham operation group (Sham group, n = 10), obstructive jaundice group (OJ group, n = 10), OJ + dexmedetomidine group (D group, n = 10), OJ+ dexmedetomidine +LY294002 group (DL group, n = 10). The expressions of phospho-Akt(p-Akt), HIF-1α(hypoxia inducible factor-1α), Akt mRNA, HIF-1αmRNA, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in different groups were evaluated. RESULTS: The lung injury score was decreased in OJ group compared with that in DL group. The expression of the HIF-1α protein, p-Akt protein, Akt mRNA, and HIF-1α mRNA in OJ group were significantly increased (p <0.05) (vs. S group). Meanwhile, these protein molecular were significantly higher in the D group than that in OJ group (p <0.05). However, the mRNA expressions of these molecular in OJ group were significantly lower than that in D group (p <0.05). The concentrations of IL-6 and TNF-α in OJ group and D group was significantly up-regulated compared with that in S group (p <0.05). Meanwhile, IL-6 and TNF-α concentrations were significantly up-regulated in DL group compared with that in group D (p <0.05). The concentrations of IL-6 and TNF-α were significantly decreased in the D group and DL group compared with that in OJ group (p <0.05). CONCLUSION: Dexmedetomidine can attenuate lung injury in obstructive jaundice rats through PI3K/Akt/HIF-1α signaling pathway. Meanwhile, dexmedetomidine can reduce the concentrations of IL-6 and TNF-α in obstructive jaundice rats.

[Systemic membrane-destabilizing distress syndrome in surgery: concept, pathogenesis, diagnosis]. / Sistemnyi membranodestabiliziruiushchii distress-sindrom v khirurgii: poniatie, patogenez, diagnostika.

AIM: To justify the concept of systemic membrane-destabilizing distress syndrome in surgery via analysis of phospholipid bilayer of cell membranes of various organs in urgent surgical abdominal diseases. MATERIAL AND METHODS: Experimental research on dogs (n=90) included modeling of peritonitis, pancreatitis, intestinal obstruction, obstructive jaundice, and post-hemorrhagic anemia. Clinical and laboratory studies were performed in patients (n=119) with acute peritonitis, severe pancreatitis, intestinal obstruction, post-hemorrhagic anemia, acute cholecystitis, gastrointestinal bleeding, benign mechanical jaundice. Lipid profile in tissues and blood cells was determined by extraction, fractionation and densitometry. Moreover, we assessed intensity of lipid peroxidation and phospholipase activity, endogenous intoxication, functional state of organs and blood cells. RESULTS: It was revealed that all above-mentioned acute abdominal diseases are followed by significant changes of lipid bilayer and dysfunction of tissues in target organs, blood cells and other organs (liver, kidney, colon and small intestine, heart, lungs, spleen, brain). Changes of phospholipid bilayer are correlated with severity and course of the disease. These data were used to determine a new complex in surgery - systemic membrane-destabilizing distress syndrome. Its concept, pathogenesis, and diagnosis are presented. It was analyzed its role in development and progression of dysregulation pathology and thanatogenesis. Evidence of its importance in the pathogenesis of surgical aggression was obtained.

Combined treatment of nonresectable cholangiocarcinoma complicated by obstructive jaundice.

BACKGROUND: The five-year survival rate for successful surgical treatment of cholangiocellular cancer is only 20-40%, and in the case of an unresectable tumor, the life expectancy does not usually exceed 6 months. Survival decreases with the presence of jaundice, due to the spread of the tumor process along the bile ducts, leading to their obstruction. We report outcomes of patients with nonresectable bile duct carcinoma complicated by obstructive jaundice treated with Photodynamic Therapy (PDT). METHODS: Combined diagnosis and treatment included percutaneous cholangiostomy, intraductal video fluorescence diagnostics, photodynamic therapy, and bile duct stenting. All patients were treated at the Sechenov University Oncology Center in Moscow. The results of treatment of 33 patients have been presented. The intraductal diagnosis of malignant bile duct lesions was performed after cholangiostomy using the endovideofluorescence module for minimally invasive surgery and endoscopy. With the use of this method, it is the first time in Russia that it has become possible to obtain a videofluorescent image of the tumor and to determine the high level of photosensitizer accumulation in all cholangiocarcinoma patients. The preparations Photolon, Radachlorin, and Photosens were employed as photosensitizers (PS). Intraductal photodynamic therapy was used to achieve the antitumor effect. Laser power density was about 200 mW/cm2. RESULTS: We present initial results, improved the diagnostic possibilities in this difficult localization of carcinoma, and demonstrated the feasibility of prolongation of life without significant deterioration of its quality. The average survival time in the treatment group is 9.5 months. CONCLUSION: The treatment of patients with nonresectable cholangiocarcinoma with Photodynamic Therapy should be an available option. In this context, the additional use of intraductal endovideofluorescence diagnostics is a highly specific technique that allows reliable detection of the photosensitizer accumulation predominantly by the tumor tissue and appears promising. As shown by our experience, flourescent localization followed by Photodynamic Therapy, enabled us to improve diagnostic techniques and treat the tumor with improved outcome.