Scoring system assessing mucosal visibility of upper gastrointestinal tract: The POLPREP scale.

BACKGROUND AND AIM: The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS: To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS: The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS: The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

On the Track of New Endoscopic Alternatives for the Treatment of Selected Gastric GISTs-A Pilot Study.

Background and Objectives: GISTs (Gastrointestinal stromal tumors) are the most common mesenchymal gastrointestinal tract tumours and are mainly located in the stomach. Their malignant potential depends on size, location, and type. Endoscopic techniques are a less invasive modality for patients not eligible for surgery. ESD (endoscopic submucosal dissection) is mainly used for the removal of smaller GISTs, with intraluminal growth and a more superficial location. Thus, R0 resection capability in some cases may be not sufficient, limited by tumour size, location in the gastric wall, and its connection level with the muscularis propria. In such cases, an endoscopic full-thickness resection can become a new alternative. In this retrospective pilot study, we evaluated ESD and hybrid resection techniques in terms of safety, efficacy, and disease recurrence for selected types of gastric GISTs. Materials and Methods: A retrospective comparison was conducted in a group of patients who underwent ESD or a hybrid technique combining endoscopic resection with endoscopic suturing using the OverStitch system (HT) for type II or III gastric GISTs. A total of 21 patients aged 70 ± 8 years underwent endoscopic resection. Seventeen lesions were treated with ESD and four with the HT. Results: R0 resection was achieved in all patients treated using HT (type III lesions) and in 53% of those treated with ESD (p = 0.08). None of the type III lesions treated with ESD were excised with R0. Lesions treated with R0 ESD resections were significantly smaller (1.76 ± 0.35 cm) than those with R1 ESD resections (2.39 ± 0.40 cm) (p < 0.01). The mean lesion size treated with the HT was 2.88 ± 0.85 cm. Conclusions: HT may be a new resection modality for large gastric GISTs with high muscularis propria connection grades. Further studies are required to evaluate its safety and efficacy and to form precise inclusion criteria for endoscopic resection techniques.

Mutational Mosaics of Cell-Free DNA from Pancreatic Cyst Fluids.

BACKGROUND: Pancreatic cyst fluids (PCFs) enriched in tumor-derived DNA are a potential source of new biomarkers. The study aimed to analyze germinal variants and mutational profiles of cell-free (cf)DNA shed into the cavity of pancreatic cysts. METHODS: The study cohort consisted of 71 patients who underwent endoscopic ultrasound fine-needle aspiration of PCF. Five malignant cysts, 19 intraductal papillary mucinous neoplasms (IPMNs), 11 mucinous cystic neoplasms (MCNs), eight serous cystic neoplasms (SCNs), and 28 pseudocysts were identified. The sequencing of 409 genes included in Comprehensive Cancer Panel was performed using Ion Proton System. The mutation rate of the KRAS and GNAS canonical loci was additionally determined using digital PCR. RESULTS: The number of mutations detected with NGS varied from 0 to 22 per gene, and genes with the most mutations were: TP53, KRAS, PIK3CA, GNAS, ADGRA2, and APC. The frequencies of the majority of mutations did not differ between non-malignant cystic neoplasms and pseudocysts. NGS detected KRAS mutations in malignant cysts (60%), IPMNs (32%), MCNs (64%), SCNs (13%), and pseudocysts (14%), with GNAS mutations in 20%, 26%, 27%, 13%, and 21% of samples, respectively. Digital PCR-based testing increased KRAS (68%) and GNAS (52%) mutations detection level in IPMNs, but not other cyst types. CONCLUSIONS: We demonstrate relatively high rates of somatic mutations of cancer-related genes, including KRAS and GNAS, in cfDNA isolated from PCFs irrespectively of the pancreatic cyst type. Further studies on molecular mechanisms of pancreatic cysts malignant transformation in relation to their mutational profiles are required.

Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?

Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among PaCa patients and assessed their possible association with the risk of disease in Poland. In the study 383 PaCa patients and 4,000 control subjects were genotyped for founder mutations in: BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1 (657del5) and PALB2 (509_510delGA, 172_175delTTGT). A statistically significant association between the 657del5 mutation and an increased risk of pancreatic cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA) was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000 (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509_510delGA and 172_175delTTGT mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8 (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000 (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1 (657del5) was associated with an increased risk of PaCa in heterozygous carriers, indicating that this mutation appears to predispose to cancer of the pancreas. By identifying pancreatic cancer risk groups, founder mutation testing in Poland should be considered for people at risk for PaCa.

Selenium as a marker of cancer risk and of selection for control examinations in surveillance.

Publication is summarization of existing data being results of literature review and our experience on usefulness of selenium as a diagnostic marker selection for control examinations in surveillance and as a marker of patients with high risk of cancers.

A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer.

BACKGROUND & AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. METHODS: Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. RESULTS: We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%). CONCLUSIONS: We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Role of endoscopic ultrasound in the characterization of solid pseudopapillary neoplasm of the pancreas.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) is an uncommon pathology of the pancreas with unpredictable malignant potential. Endoscopic ultrasound (EUS) assessment plays a vital role in lesion characterization and confirmation of the tissue diagnosis. However, there is a paucity of data regarding the imaging assessment of these lesions. AIM: To determine the characteristic EUS features of SPN and define its role in preoperative assessment. METHODS: This was an international, multicenter, retrospective, observational study of prospective cohorts from 7 large hepatopancreaticobiliary centers. All cases with postoperative histology of SPN were included in the study. Data collected included clinical, biochemical, histological and EUS characteristics. RESULTS: One hundred and six patients with the diagnosis of SPN were included. The mean age was 26 years (range 9 to 70 years), with female predominance (89.6%). The most frequent clinical presentation was abdominal pain (80/106; 75.5%). The mean diameter of the lesion was 53.7 mm (range 15 to 130 mm), with the slight predominant location in the head of the pancreas (44/106; 41.5%). The majority of lesions presented with solid imaging features (59/106; 55.7%) although 33.0% (35/106) had mixed solid/cystic characteristics and 11.3% (12/106) had cystic morphology. Calcification was observed in only 4 (3.8%) cases. Main pancreatic duct dilation was uncommon, evident in only 2 cases (1.9%), whilst common bile duct dilation was observed in 5 (11.3%) cases. One patient demonstrated a double duct sign at presentation. Elastography and Doppler evaluation demonstrated inconsistent appearances with no emergence of a predictable pattern. EUS guided biopsy was performed using three different types of needles: Fine needle aspiration (67/106; 63.2%), fine needle biopsy (37/106; 34.9%), and Sonar Trucut (2/106; 1.9%). The diagnosis was conclusive in 103 (97.2%) cases. Ninety-seven patients were treated surgically (91.5%) and the post-surgical SPN diagnosis was confirmed in all cases. During the 2-year follow-up period, no recurrence was observed. CONCLUSION: SPN presented primarily as a solid lesion on endosonographic assessment. The lesion tended to be located in the head or body of the pancreas. There was no consistent characteristic pattern apparent on either elastography or Doppler assessment. Similarly SPN did not frequently cause stricture of the pancreatic duct or common bile duct. Importantly, we confirmed that EUS-guided biopsy was an efficient and safe diagnostic tool. The needle type used does not appear to have a significant impact on the diagnostic yield. Overall SPN remains a challenging diagnosis based on EUS imaging with no pathognomonic features. EUS guided biopsy remains the gold standard in establishing the diagnosis.

Endoscopic submucosal dissection for treatment of gastric subepithelial tumors (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is a well-accepted method for removing superficial mucosal tumors; however, there is limited data on the use of this method for removing subepithelial tumors. OBJECTIVE: To investigate the efficacy, safety, and outcome of ESD for gastric subepithelial tumors and determine factors related to treatment success. DESIGN: Retrospective analysis of a prospectively maintained database. SETTING: Single tertiary academic center. PATIENTS AND INTERVENTIONS: From April 2007 to November 2010, 37 patients with gastric subepithelial tumors were treated with ESD. MAIN OUTCOME MEASUREMENTS: Macroscopically and microscopically complete en block resection rate (R0), complication rate, and endosonographic features predictive of R0 resection. RESULTS: The median tumor diameter was 25.0 mm, (range 10-60 mm, IQR 17-37). The overall rate of R0 resections was 81.1% (30/37, 95%CI: 61.8-90.2%), including 100% (15/15, 95%CI: 78.2-100.0%) of tumors from the submucosa and 68.2% (15/22, 95%CI: 45.1-86.1%) of tumors from the muscularis propria. Seventeen patients had a final diagnosis of gastrointestinal stromal tumor. The severe complication (perforation) rate was 5.4% (2/37, 95%CI: 0.0-9.5%). One patient required surgery; the other was treated conservatively. No recurrence was observed in patients with R0 resections at a median follow up of 21.0 months (IQR 11-35). Successful R0 resections were predicted by the observation of no, or only narrow, tumor connections with the underlying muscle layer during EUS (OR=35.0, 95%CI: 3.7-334.4, p=0.001). LIMITATIONS: Single-center, retrospective analysis, short follow-up. CONCLUSIONS: ESD is an effective and relatively safe method for removing gastric subepithelial tumors. Endoscopic ultrasonography findings can predict complete tumor resections.

Aggressive surgical management of recurrent lymph node and pancreatic head metastases of resected fibrolamellar hepatocellular carcinoma: a case report.

CONTEXT: Fibrolamellar hepatocellular carcinoma is a rare liver tumor with the propensity to metastasize to the lymph nodes months or years after initial surgery. However, its metastatic spread to the pancreas was previously reported only in a child. CASE REPORT: We present an unusual case of a young female patient who was repeatedly treated by surgical excision of abdominal and mediastinal lymph node recurrences between 2 and 6 years after left hepatic lobectomy for fibrolamellar hepatocellular carcinoma. At 8 years following her initial surgery, the patient was diagnosed with pancreatic head metastasis and a pancreaticoduodenectomy was performed. Postoperative course was uneventful and the patient did not experience recurrence within the last 18 months. CONCLUSION: The metastasis of fibrolamellar hepatocellular carcinoma to the pancreas is highly exceptional but possible and its excision appears warranted as well.

Pancreatoduodenectomy with a modified duct-to-mucosa pancreaticojejunostomy: an analysis of 101 consecutive patients.

BACKGROUND/AIMS: The aim of the study was to analyze in-hospital morbidity and mortality after pancreatoduodenectomy (PD) with a modified duct-to-mucosa pancreaticojejunostomy. METHODOLOGY: We retrospectively analyzed 101 consecutive patients who underwent PD at our center between January 2002 and December 2010. Two-layered duct-to-mucosa pancreaticojejunostomy was performed over an internal transanastomotic stent in all patients. RESULTS: The overall in-hospital morbidity and mortality rate was 48% and 6%, respectively. Three patients died as a consequence of local complications including mesenteric ischemia in two and acute necrotizing pancreatitis in one case. Pancreatic fistula occurred in one (1%) patient and was treated conservatively with good outcome. The wound infection was the most common surgical complication (20/101; 20%) and occurred more often in patients who had a biliary stent inserted endoscopically prior to surgery (15/38; 39%), as compared to those without the stent (5/63; 8%; p=0.0003). CONCLUSIONS: The results of the present study suggest that a two-layered duct-to-mucosa pancreaticojejunostomy with internal transanastomotic stent is a safe anastomosis, associated with a very low risk of pancreatic fistula. The presence of a biliary stent at the time of surgery represents a risk factor for the development of postoperative wound infection.

[Portal biliopathy presenting itself as a massive vericeal bleeding--case report]. / Krwotok z zylaków przelyku jako pierwszy objaw kini czny biliopatii wrotnej--opis przypadku.

This article presents a rare case of portal biliopathy, a secondary cholangiopathy, in a young man whose first clinical manifestation was bleeding from esophageal varices. Portal biliopathy may mimic primary sclerosing cholangitis and it can develop secondary to portal vein thrombosis usually acquired in early childhood. Narrowing and dilatation of biliary tree develops as a consequence of compression of common bile duct by collaterals. Clinical symptoms are mainly cholestatic jaundice and abdominal pain. Complications include recurrent cholangitis and secondary biliary cirrhosis. The article provides information on the pathogenesis, clinical symptoms and treatment of portal biliopathy and problems related to differential diagnosis with primary sclerosing cholangitis (PSC).

Optimal Endoscopic Resection Technique for Selected Gastric GISTs. The Endoscopic Suturing System Combined with ESD-a New Alternative?

Background and Study Aim: In terms of therapeutic management, gastrointestinal stromal tumors (GISTs) seem to be the most difficult group of subepithelial gastrointestinal lesions (SELs). Despite various treatment option, choice of optimal management remains a dilemma in daily practice. Our aim was to evaluate a new hybrid resection technique of gastric GISTs type III as a modality of endoscopic full-thickness resection. Methods: Three males and one female (mean age of 68) were qualified for the procedure. Endoscopic full-thickness resections consisted of the endoscopic resection combined with suturing by Apollo OverStitch System. The main inclusion criterium was a complete diagnosis of GISTs (computed tomography (CT), endoscopic ultrasound (EUS), fine-needle biopsy (FNB)) with the evaluation of the tumor features, especially, the location in the gastric wall. All of the tumors were type III with a diameter between 20-40 mm. The lesions were located in the corpus (1), antrum (1) and between gastric body and fundus (2). All procedures were performed in 2019. Results: The technical and therapeutic success rate was 100% and the mean resection time 107.5 min. Neither intra- nor postprocedural complications were observed. In all four cases, R0 resection was achieved. Histopathologic assessment confirmed GIST with <5mitose/50HPF in all of the tumors, with very low risk. Conclusion: Based on our outcomes, endoscopic resection combined with the sewing by Apollo OverStitch of gastric GISTs type III, with the diameter between 20-40 mm, seems to be an effective therapeutic option with a good safety profile, however further studies with a larger treatment group are needed.

Prevalence of 'deep' rectal varices in patients with cirrhosis: an EUS-based study.

BACKGROUND: Endoscopic ultrasound (EUS) permits identification of dilated veins of the intrinsic rectal venous system (deep varices) in portal hypertension. The aim of this cross-sectional study was to assess the prevalence of, and risk factors for, deep rectal varices, using EUS. METHODS: A cohort of 96 patients with cirrhosis was studied. Both routine rectoscopy and rectal EUS were performed. Deep varices were assessed as peri-rectal and para-rectal. A three-grade scale was used to assess the size of the deep varices. RESULTS: On rectoscopic examination, congestive rectopathy was seen in 11(11%) patients, blue veins in 36(38%) and rectal varices in 13 (14%). On EUS, deep varices were seen in 49(51%) subjects. Small peri-rectal varices were seen in 29 (30%) patients and large peri-rectal varices in 10 (10%). Small para-rectal varices were seen in 22 (23%) patients and large para-rectal in 13 (14%). Of the 83 patients without rectal varices on rectoscopy, 39 (47%) had varices detectable with EUS. Patients with large deep varices had more advanced liver disease and significantly thicker rectal wall. They did not differ from other patients in terms of the other analysed factors. CONCLUSION: EUS permits identification of deep rectal varices in a large proportion of patients without detectable varices on rectoscopy. Unlike in previous study, we found that the presence of large deep rectal varices correlates with the degree of liver failure and thickness of rectal wall but not with the grade of portal hypertension in the oesophagus or the stomach. The clinical significance of these varices is uncertain and requires further study.

Partington-rochelle pancreaticojejunostomy for chronic pancreatitis: analysis of outcome including quality of life.

BACKGROUND/AIMS: Obstruction of the main pancreatic duct in chronic pancreatitis (CP) leads to an increased intraductal and intraparenchymal pressure causing pain. In this study we evaluated the outcome of surgical treatment of CP including the quality of life following Partington-Rochellepancreaticojejunostomy (PRP) performed for intractable pain. METHODOLOGY: Between July 2002 and May 2008, PRP was performed in 17 patients in whom the diameter of the main pancreatic duct exceeded 7mm and there was no inflammatory tumor in the pancreatic head. Perioperative morbidity and mortality were analyzed in all patients. The long term outcome including the quality of life (Karnofsky index) was evaluated in 9 patients who were followed with a mean 28 (range 13-60) months since surgery. RESULTS: Complications in the postoperative period were found in 3 (18%) patients including 1 death due to a myocardial infarction shortly after surgery. All patients submitted to the long-term evaluation reported a significant (p < 0.0001) pain reduction by an average of 6.2 (5-8) points in a 10-points visual analogue scale. The Karnofsky index increased significantly from a mean 52% (40-70%) before surgery up to 82% (70-90%) following surgery and long-term. CONCLUSIONS: PRP leads to a substantial quality of life improvement in patients with CP.

[Benign solid tumors of the liver--review of current knowledge]. / Lagodne lite guzy watroby--aktualny stan wiedzy.

Benign solid tumors of the liver may be one of the great diagnostic difficulties among the hepatic problems. The most common of them are: haemangiomas, adenomas, nodular regenerative hyperplasia (NRH) and focal nodular hyperplasia (FNH). There are several useful ways of imaging for those lesions (USG, CT, MR), which are helpful in decision-making and further management. This article presents a summary of the main information on benign solid tumors of the liver based on internet database MEDLINE. Also, it contains some proceedings of treatment and control for patients with those lesions, which can help to differentiate benign and malignant hepatic tumors.

Endoscopic Ultrasound-Guided Treatment of Gastric Varices Using Coils and Cyanoacrylate Glue Injections: Results after 1 Year of Experience.

BACKGROUND AND AIMS: Gastric varices (GVs) occur in 20% of patients with portal hypertension. GVs are associated with a 65% risk of bleeding over the course of 2 years and have a mortality rate of up to 20%. The standard treatment for GVs is obliteration with cyanoacrylate (CYA). This study presents our experience with combined therapy (vascular coils and CYA) under endoscopic ultrasound (EUS) guidance. METHODS: 16 patients (9 male and 7 female) were included into our study. Etiology of portal hypertension included: portal vein thrombosis (PVT) (31.0%), isolated splenic vein thrombosis (SVT) (25.0%), alcoholic cirrhosis (12.5%), hepatitis C cirrhosis (19.0%), and alcoholic cirrhosis with PVT (12.5%). Varices type GOV-2 were diagnosed in 8 patients, type IGV-1 and IGV-2 in 6 and 2 patients, respectively. Indications for treatment were based on endoscopic and endosonographic evaluations of GVs. Inclusion and exclusion criteria were also specified. Technique depended on the size of varices (different size of coils + CYA additionally). The results were based on the achievement of technical success, therapeutic effects, and number of adverse events. Average follow-up period was 327 days. RESULTS: From January to August 2017, 16 patients were treated with EUS-guided obliteration of GVs using vascular coils only or coils with CYA injections. 6 (37.5%) and 10 (62.5%) patients underwent primary and secondary prophylaxis for hemorrhage, respectively. Technical success was achieved in 15 patients (94.0%). Mean numbers of implanted coils and CYA volume during one procedure were 1.7 and 2 mL, respectively. Therapeutic success was achieved in all patients treated with the combination. There were no serious complications such as embolization or death due to the procedure. Three patients (19.0%) had transient abdominal pain and two (12.5%) had transient fever. 1 patient had clinical symptoms of gastrointestinal bleeding. CONCLUSIONS: Based on our retrospective research we have concluded, that EUS-guided implantation of intravascular coils combined with cyanoacrylate injections is an effective method of treatment with an acceptable number of complications.

Initial experience with endoscopic ultrasound-guided gallbladder drainage.

INTRODUCTION: Patients with acute cholecystitis who are unsuitable for cholecystectomy undergo conservative treatment or percutaneous transhepatic gallbladder drainage. As these two methods are not always successful, further treatment options are needed. One increasingly popular method is endoscopic ultrasound-guided gallbladder drainage (EUSGBD), whereby stents are placed so as to create a permanent fistula connecting the gallbladder to the stomach or the duodenal bulb, thus enabling drainage of its contents to the gastrointestinal tract. AIM: To present our early experience with EUSGBD for the treatment of cholecystitis in patients who are not suitable for cholecystectomy. MATERIAL AND METHODS: The procedure was performed in 5 patients with acute cholecystitis. Two patients also had symptoms of biliary obstruction due to pancreatic head cancer. An ultrasound endoscope was used to create a fistula between the gallbladder and the stomach or between the gallbladder and the duodenal bulb, in which a self-expandable metallic stent (SEMS) was placed. RESULTS: All procedures were performed with no perioperative complications. In all patients, the clinical symptoms of cholecystitis subsided within 3-15 days. In those patients who also showed symptoms of biliary obstruction, these symptoms subsided within 3-6 days following the procedure. CONCLUSIONS: The EUSGBD seems to be an effective and safe treatment for acute cholecystitis in patients unsuitable for cholecystectomy. It can also be used to treat jaundice caused by obstruction of the common bile duct, when no other methods can be used. The method is particularly promising in cases of concurrent acute cholecystitis and common bile duct obstruction.

Dysregulation of Mucosal Membrane Transporters and Drug-Metabolizing Enzymes in Ulcerative Colitis.

Intestinal transporters and metabolizing enzymes are the important factors of the intestinal absorption barrier. Because there is evidence that their expression and function may be affected during inflammatory conditions, we investigated gene expression, protein abundance, and regulation of relevant intestinal transporters and metabolizing enzymes in the intestinal mucosa of patients with ulcerative colitis (UC). Specimens from inflamed and noninflamed tissues of 10 patients with UC as well as colonic control tissues of 10 patients without inflammation were subjected to gene (9 enzymes, 15 transporters, 9 cytokines) and microRNA (N = 54) expression analysis. Protein abundance was quantified by liquid chromatography-tandem mass spectrometry-based targeted proteomics. Gene expression of several metabolizing enzymes (e.g., CYP2C9, UGT1A1) and transporters such as ABCB1 (ABCB1), ABCG2 (ABCG2), and monocarboxylate transporter 1 (MCT1, SLC16A1) were significantly decreased during inflammation and negatively correlated to microRNAs. On contrary, multidrug resistance-protein 4 (MRP4, ABCC4), organic anion-transporting polypeptide 2B1 (OATP2B1, SLCO2B1), and organic cation transporter-like 2 (ORCTL2, SLC22A18) were significantly elevated in inflamed tissue. However, at protein level, these findings could only be confirmed for MCT1. UC is associated with complex changes in the intestinal expression of enzymes, transporters, cytokines, and microRNAs, which may affect efficacy of anti-inflammatory drug therapy or the disease state itself.