Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study.

BACKGROUND: Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer. METHODS: A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023. RESULTS: In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival. CONCLUSIONS: IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

Tracking incidentally discovered pancreatic cysts smaller than 30 mm: Natural course and predictors of malignancy.

BACKGROUND AND AIMS: The aim of this study was to assess the natural course and predictors of malignancy in incidentally detected small pancreatic cysts (PCs). METHOD: We retrospectively included patients with PCs smaller than 30 mm followed up with the same cross-sectional imaging modality at least 12 months apart between January 2010 and December 2019 in three academic institutions. Cyst growth, pancreatic cancer incidence, and associated factors associated with pancreatic cancer were analyzed. RESULTS: A total of 1109 patients were followed up for a median of 34 months (range, 12‒118 months). Cyst growth and rapid cyst growth (≥ 5 mm/2 years) during follow-up were observed in 20.7% and 8.3%, respectively, both with higher rates for 15‒30 mm sized PCs. Eight patients were diagnosed with pancreatic cancer. The standardized incidence ratio for pancreatic cancer in small PCs was calculated as 5.2 [95% Confidence interval (CI): 1.3‒20.5].  The development of pancreatic cancer was associated with rapid growth [hazard ratio (HR): 8.1, 95% CI: 1.5‒43.4, p = 0.015] and newly developed worrisome features (HR: 11.7, 95% CI: 1.7‒79.6, p = 0.012) in competing risk analysis. CONCLUSIONS: One-fifth of small incidentally detected PCs increased in size. Rapid growth and newly developed worrisome features were predictors of malignancy.

Incidence and risk of pancreatic cancer in patients with chronic pancreatitis: defining the optimal subgroup for surveillance.

We aimed to present the incidence and risk factors for pancreatic cancer in a multicenter retrospective cohort of patients with chronic pancreatitis (CP). Patients with ICD-10 codes for CP (K86.0, K86.1) who underwent abdominal CT or MRI between January 2010 and December 2021 in seven academic hospitals were analyzed. After exclusions, we identified 727 patients with definite CP with a median follow-up of 3.6 years (range 1.0‒12.9). During 3290 person-years of observation, pancreatic cancers were diagnosed in 16 patients (2.20%, 0.49% per year) after a median follow-up of 2.4 years (range 1.4‒6.6), with an age- and sex-standardized incidence ratio of 18.1 (95% CI 10.4‒29.5). The underlying CPs in the 16 pancreatic cancers were classified as chronic obstructive pancreatitis (10, 63%), chronic obstructive and calcifying pancreatitis (4, 25%), chronic calcifying pancreatitis (1, 6%), and autoimmune pancreatitis (1, 6%). Factors associated with pancreatic cancer development included age (HR 4.830, p = 0.006), parenchymal calcification (HR 0.213, p = 0.003), pancreatic duct stricture (HR 2.706, p = 0.048), and serum CA 19‒9 level (HR 3.567, p = 0.014). After adjustment, age over 60 years (HR 4.540, p = 0.009) and serum CA 19‒9 levels greater than 100 U/mL (HR 3.528, p = 0.015) were independent risk factors for pancreatic cancer.

Analysis of symptomatic recurrences of common bile ducts stones after endoscopic removal: Factors related to early or multiple recurrences.

ABSTRACT: Early or multiple recurrences of symptomatic common bile duct (CBD) stones are troublesome late complications after endoscopic stone removal. We aimed to determine the factors related to early or multiple recurrences of CBD stones.We retrospectively analyzed patients who underwent endoscopic CBD stone extraction in a single institute between January 2006 and December 2015. Patients were divided into 2 groups according to the number and interval of CBD stone recurrences: single versus multiple (≥2) and early (<1.5 years) versus late (≥1.5 years) recurrence.After exclusion, 78 patients were enrolled and followed up for a median of 1974 (IQR: 938-3239) days. Twenty-seven (34.6%) patients experienced multiple recurrences (≥2 times), and 26 (33.3%) patients experienced early first recurrence (<1.5 years). In the multivariate analysis, CBD angulation was independently related to multiple CBD stone recurrence (OR: 4.689, P = .016), and endoscopic papillary large balloon dilation was independently related to late first CBD stone recurrence (OR: 3.783, P = .025). The mean CBD angles were more angulated with increasing instances of recurrence (0, 1, 2, 3, and ≥4 times) with corresponding values of 150.3°, 148.2°, 143.6°, 142.2°, and 126.7°, respectively (P = .011). The period between the initial treatment and first recurrence was significantly longer than the period between the first and second recurrence (P = .048).In conclusion, greater CBD angulation is associated with the increased number of CBD stone recurrence, and EPLBD delays the recurrence of CBD stones after endoscopic CBD stone removal.

CD40 Agonists Alter the Pancreatic Cancer Microenvironment by Shifting the Macrophage Phenotype toward M1 and Suppress Human Pancreatic Cancer in Organotypic Slice Cultures.

Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163+ (predominant in M2 macrophages) and FOXP3+ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163+ expression had shorter overall survival than those with low CD163+ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR+ (predominant in M1 macrophages) and a decrease in CD163+ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR+ and decrease CD163+ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Unilateral versus bilateral Y-type stent-in-stent metal stent insertions in inoperable malignant hilar biliary strictures: A multicenter retrospective study.

BACKGROUND: To date, there is controversy regarding unilateral versus bilateral stent placement in patients with malignant hilar biliary strictures (MHBSs). The aim of this study was to compare the clinical outcomes and complications of unilateral and bilateral (stent-in-stent method) stent placements for these patients. METHODS: We conducted a multicenter retrospective analysis of patients with inoperable MHBS who underwent endoscopic self-expandable metal stent (SEMS) placement from January 2009 to December 2019. Two groups classified according to the stent procedure method were compared for demographic, procedural, and postprocedure factors. Survival analysis for patency loss and overall survival was also conducted. RESULTS: A total of 236 subjects were included. A superior technical success rate was found in the unilateral stent group (98.8% vs. 82.5%, P < 0.001), whereas the clinical success rate was higher in the bilateral group (85.7% vs. 70.5%, P = 0.028). There was no significant difference with respect to complications or patency loss, and the bilateral group had better overall survival (P < 0.01). In the Cox proportional hazard model, MHBSs from lymph node compression were associated with a higher risk of death (HR = 9.803, P = 0.003). In contrast, bilateral SEMS insertion showed reduced postprocedural mortality (HR = 0.316, P = 0.001). CONCLUSIONS: Y-type stent-in-stent bilateral SEMSs are technically difficult but demonstrated more favorable overall survival for palliative bile drainage of inoperable MHBS patients compared to unilateral insertions.

The Safety of Radiofrequency Ablation Using a Novel Temperature-Controlled Probe for the Treatment of Residual Intraductal Lesions after Endoscopic Papillectomy.

BACKGROUND/AIMS: Treatment of residual intraductal lesions after endoscopic papillectomy for ampullary adenomas is relatively difficult. Few studies have been conducted using intraductal radiofrequency ablation (RFA) in the treatment of such lesions, and no study has aimed to reduce the side effects of excessive heat caused by RFA. Recently, a temperature-controlled RFA probe was developed to avoid excessive heat. This study aimed to investigate the safety of this new RFA probe in the treatment of intraductal lesions of ampullary adenoma. METHODS: Patients who received RFA for residual intraductal lesions after endoscopic papillectomy between November 2017 and June 2019 were retrospectively reviewed. A novel temperature- controlled probe (ELRA) was used for intraductal RFA, and clinical data including adverse events were collected. RESULTS: Ten patients were included in this study. Intraductal adenomas showed low-grade dysplasia in eight patients and high-grade dysplasia in two patients. The median diameter of intraductal adenomas was 9 mm (range, 5 to 10 mm) in the common bile duct and 5 mm (range, 4 to 11 mm) in the pancreatic duct. Adverse events occurred in three patients (30.0%), of which two were mild pancreatitis and one was asymptomatic biliary stricture. Over a median follow-up period of 253 days, only one patient underwent additional surgery, as the remainder showed no adenomatous lesions on follow-up biopsies. CONCLUSIONS: The new temperature-controlled RFA probe can be used with acceptable safety for the treatment of residual intraductal lesions after endoscopic papillectomy. Further evaluation through future prospective studies is needed.

A systematic review and meta-analysis of effects of menopausal hormone therapy on cardiovascular diseases.

A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies was conducted to assess the association between menopausal hormone therapy and cardiovascular disease. The PubMed and EMBASE databases were searched for articles published from 2000 to 2019, using review methods based on a previous Cochrane review. Quality assessment of RCTs and observational studies was conducted using the Jadad scale and the Newcastle-Ottawa Scale, respectively. A total of 26 RCTs and 47 observational studies were identified. The study populations in the RCTs were older and had more underlying diseases than those in the observational studies. Increased risks of venous thromboembolism [summary estimate (SE), 95% confidence interval (CI): RCTs, 1.70, 1.33-2.16; observational studies, 1.32, 1.13-1.54] were consistently identified in both study types, whereas an increased risk of stroke in RCTs (SE: 1.14, 95% CI: 1.04-1.25) and a decreased risk of myocardial infarction in observational studies (SE: 0.79, 95% CI: 0.75-0.84) were observed. Differential clinical effects depending on timing of initiation, underlying disease, regimen type, and route of administration were identified through subgroup analyses. These findings suggest that underlying disease and timing of initiation should be carefully considered before starting therapy in postmenopausal women.

Metachronous Development of Peritoneal Carcinomatosis in a Patient with Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is a rare and unique type of chronic pancreatitis. The prognosis of AIP, particularly when associated with pancreatic cancer or a related malignancy, is not known. Only a few cases, where metachronous pancreas-related cancer developed during follow-up, have been reported. Most of these patients either underwent surgery or steroid therapy. This paper reports a case of a 66-year-old woman with untreated type I AIP who developed peritoneal carcinomatosis more than 2 years later. Initially, the patient had a markedly elevated serum IgG4 level and a diffuse, infiltrative mass-like lesion in the pancreatic head, in which the biopsy results were consistent with type I AIP. The patient was not treated with steroids because of a cerebellar infarction. Twenty-eight months after the diagnosis of AIP, peritoneal carcinomatosis developed without noticeable changes in the pancreas from the initial findings.

Prolonged hyperamylasemia in patients with acute pancreatitis is associated with recurrence of acute pancreatitis.

Serum amylase levels in patients with acute pancreatitis often remain or fluctuate above the upper normal limit for over a week. This study investigated the clinical characteristics of patients with prolonged hyperamylasemia and their prognoses, including recurrence.We retrospectively analyzed patients with first attacks of acute pancreatitis in a single center between March 2010 and December 2016. Patients were divided into 2 groups according to normalization of the serum amylase levels within a week.A total of 313 patients were enrolled after exclusion. The serum amylase levels were normalized within a week in 205 patients (65.5%, group 1) and elevated over a week in 108 patients (34.5%, group 2). Group 2 was more related to alcohol, higher computed tomography (CT) severity index, local pancreatic complication, and moderately severe pancreatitis than group 1 (P < .05). Recurrent pancreatitis developed significantly more in group 2 (39.8%) than in group 1 (19.5%) (P < .001). The factors related to recurrent pancreatitis were amylase group, sex, alcohol, CT severity index, necrosis, and severity of pancreatitis (P < .05). Multivariate analysis showed that recurrent pancreatitis was independently associated with amylase group (odds ratio [OR] 2.123, 95% confidence interval [CI]= 1.227-3.673, P = .007) and alcohol (OR 2.023, 95% CI 1.134-3.611, P = .017).In conclusion, prolonged hyperamylasemia over a week is associated with recurrence of acute pancreatitis.

Subsets associated with developing acute pancreatitis in patients with severe hypertriglyceridemia and the severity of pancreatitis.

BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HTG) is a rare but well-recognized cause for acute pancreatitis (AP). This study aimed to determine subsets related to development of AP in patients with severe HTG and the severity of HTG-induced AP (HTG-AP). METHODS: Patients who had severe HTG (serum triglyceride level >1,000 mg/dL) more than once between Jan. 2010 and Dec. 2017 in a single institute were evaluated retrospectively. Patients were divided into two groups, with AP or without AP, and were compared. HTG-APs in patients with severe HTG were compared to APs due to other causes during the same period. RESULTS: Sixty-three patients (19.3%) presented with AP of a total 326 patients with severe HTG. The AP group displayed younger age, more alcohol consumption and diabetes mellitus, and higher initial/maximum serum levels of triglyceride, glucose, HbA1c, total cholesterol, and calculated non-high-density lipoprotein cholesterol (p < 0.05). HTG-APs were clinically more severe compared with 277 APs due to other causes in terms of CRP (p < 0.001), CT severity index (p = 0.002), revised Atlanta classification (p < 0.001), and hospital stay (p = 0.011). In logistic regression analysis, maximum serum triglyceride level (OR 2.706, p = 0.015), alcohol consumption amount (OR 5.292, p < 0.001), and age (OR 0.358, p = 0.017) were independently associated with development of AP in patients with severe HTG. CONCLUSIONS: Development of AP in patient with severe HTG was independently associated with younger age, higher serum TG level, and more alcohol consumption. HTG-APs are clinically more severe than APs due to other causes.

Organotypic slice cultures of pancreatic ductal adenocarcinoma preserve the tumor microenvironment and provide a platform for drug response.

BACKGROUND: /Objective: The conventional models currently used to evaluate various anti-tumor therapeutic agents are not sufficient for representing human pancreatic ductal adenocarcinoma (PDA), which has a unique tumor microenvironment. We aimed to produce an organotypic slice culture model from human PDA that resembles the in vivo situation and to evaluate the responses of PDA slices to established cytotoxic drugs. METHODS: PDA tissues were obtained from 10 patients who underwent pancreatic resection. The tissues were sliced by a vibratome, and the tumor slices were then cultured. The viability of tumor slices during slice culture was evaluated using H&E and immunohistochemical staining, and stromal cells were demonstrated. The effects of cytotoxic drugs on PDA cell lines and slices were analyzed. RESULTS: Tumor slices maintained their surface areas and tissue viability for at least five days during culture. Preserved proliferation and apoptosis in tumor slices were observed by the expression of Ki-67 and cleaved caspase-3. Stromal cells including macrophages (CD68+ and CD163+), T cells (CD3+, CD8+, and FOXP3+), and myeloid cells (CD11b+) were present throughout the culture period. Staurosporine, gemcitabine, and cisplatin treatment of PDA cell lines and tumor slices exerted proportional cytotoxic effects in terms of MTT viability, tumor cell number, and Ki-67 and cleaved caspase-3 expression. CONCLUSIONS: Organotypic human PDA slice cultures preserved their viability and tumor microenvironment for at least five days during slice culture. PDA slice culture appears to be a feasible preclinical test model to assess the response to anti-tumor agents.

[Treatment of Pancreatic Fluid Collections].

Pancreatic Fluid Collection (PFC) develops as a result of acute pancreatitis, chronic pancreatitis, trauma, and postoperation. Although percutaneous drainage, surgery and Endoscopic Retrograde Panceatogram are used as conventional treatments in complicated PFC, the clinical course of PFC is unsatisfactory due to its clinical success rate and the risk of procedure-related complications. Endoscopic ultrasonography-guided transmural drainage of PFC is a safe and effective modality for the management of PFC, particularly in patients with pancreas necrosis. A range of techniques and stents have been introduced and a newly designed metal stent is now available.

Outcome of donor biliary complications following living donor liver transplantation.

Background/Aims: Biliary complications are the most common donor complication following living donor liver transplantation (LDLT). The aim of this study is to investigate the long-term outcomes of biliary complications in right lobe adult-to-adult LDLT donors, and to evaluate the efficacy of endoscopic treatment of these donors. METHODS: The medical charts of right lobe donors who developed biliary complications between June 2000 and January 2008 were retrospectively reviewed. RESULTS: Of 337 right lobe donors, 49 developed biliary complications, including 36 diagnosed with biliary leakage and 13 with biliary stricture. Multivariate analysis showed that biliary leakage was associated with the number of right lobe bile duct orifices. Sixteen donors, five with leakage and 11 with strictures, underwent endoscopic retrograde cholangiography (ERC). ERC was clinically successful in treating eight of the 11 strictures, one by balloon dilatation and seven by endobiliary stenting. Of the remained three, two were treated by rescue percutaneous biliary drainage and one by conservative care. Of the five patients with leakage, four were successfully treated using endobiliary stents and one with conservative care. In overall, total 35 improved with conservative treatment. All inserted stents were successfully retrieved after a median 264 days (range, 142 to 502) and there were no recurrences of stricture or leakages during a median follow-up of 10.6 years (range, 8 to 15.2). Conclusions: All donors with biliary complications were successfully treated non-surgically, with most improving after endoscopic placement of endobiliary stents and none showing recurrence on long term follow-up.

Long-lived pancreatic ductal adenocarcinoma slice cultures enable precise study of the immune microenvironment.

Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies. Immune cells, including T cells (CD3+, CD8+, and FOXP3+) and macrophages (CD68+, CD163+ and HLA-DR+), as well as stromal myofibroblasts (αSMA+) were present throughout the culture period. Global profiling of the PDA proteome before and after 6 d slice culture indicated that the majority of the immunological proteins identified remain stable during the culture process. Cytotoxic effects of drug treatment (staurosporine, STS and cycloheximide, CHX) on PDA slices culture confirmed that this system can be used to assess functional response and cell survival following drug treatment in both a treatment time- and dose-dependent manner. Using multicolor immunofluorescence, we stained live slices for both cancer cells (EpCAM+) and immune cells (CD11b+ and CD8+). Finally, we confirmed that autologous CFSE-labeled splenocytes readily migrate into co-cultured tumor slices. Thus, our present study demonstrates the potential to use tumor slice cultures to study the immune microenvironment of PDA.

Role of immune cells in pancreatic cancer from bench to clinical application: An updated review.

BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells. METHODS: We searched PubMed for all relevant English language articles published up to March 2016. They included clinical trials, experimental studies, observational studies, and reviews. Trials enrolled at Clinical trial.gov were also searched. RESULTS: PC induces an immunosuppressive microenvironment, and intratumoral activation of immunity in PC is attenuated by inhibitory signals that limit immune effector function. Multiple types of immune responses can promote an immunosuppressive microenvironment; key regulators of the host tumor immune response are dendritic cells, natural killer cells, macrophages, myeloid derived suppressor cells, and T cells. The function of these immune cells in PC is also influenced by chemotherapeutic agents and the components in tumor microenvironment such as pancreatic stellate cells. Immunotherapy of PC employs monoclonal antibodies/effector cells generated in vitro or vaccination to stimulate antitumor response. Immune therapy in PC has failed to improve overall survival; however, combination therapies comprising immune checkpoint inhibitors and vaccines have been attempted to increase the response. CONCLUSION: A number of studies have begun to elucidate the roles of immune cell subtypes and their capacity to function or dysfunction in the tumor microenvironment of PC. It will not be long before immune therapy for PC becomes a clinical reality.

mRNA expression of CDH3, IGF2BP3, and BIRC5 in biliary brush cytology specimens is a useful adjunctive tool of cytology for the diagnosis of malignant biliary stricture.

Although advances have been made in diagnostic tools, the distinction between malignant and benign biliary strictures still remains challenging. Intraductal brush cytology is a convenient and safe method that is used for the diagnosis of biliary stricture, but, low sensitivity limits its usefulness. This study aimed to demonstrate the usefulness of mRNA expression levels of target genes in brush cytology specimens combined with cytology for the diagnosis of malignant biliary stricture. Immunohistochemistry for cadherin 3 (CDH3), p53, insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3), homeobox B7 (HOXB7), and baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) was performed in 4 benign and 4 malignant bile duct tissues. Through endoscopic or interventional radiologic procedures, brush cytology specimens were prospectively obtained in 21 and 35 paitents with biliary strictures. In the brush cytology specimens, the mRNA expressions levels of 5 genes were determined by real-time polymerase chain reaction. Immunohistochemistry for CDH3, p53, IGF2BP3, HOXB7, and BIRC5 all showed positive staining in malignant tissues in contrast to benign tissues, which were negative. In the brush cytology specimens, the mRNA expression levels of CDH3, IGF2BP3, HOXB7, and BIRC5 were significantly higher in cases of malignant biliary stricture compared with cases of benign stricture (P = 0.006, P < 0.001, P < 0.001, and P = 0.001). The receiver-operating characteristic curves of these 4 mRNAs demonstrated that mRNA expression levels are useful for the prediction of malignant biliary stricture (P = 0.006, P < 0.001, P < 0.001, and P = 0.002). The sensitivity and specificity, respectively, for malignant biliary stricture were 57.1% and 100% for cytology, 57.1% and 64.3% for CDH3, 76.2% and 100% for IGF2BP3, 71.4% and 57.1% for HOXB7, and 76.2% and 64.3% for BIRC5. When cytology was combined with the mRNA levels of CDH3, IGF2BP3, or BIRC5, the sensitivity for malignant biliary stricture improved to 90.5%. The measurement of the mRNA expression levels of CDH3, IGF2BP3, and BIRC5 by real-time polymerase chain reaction combined with cytology was useful for the differentiation of malignant and benign biliary strictures in brush cytology specimens.

Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation.

Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach.

Effect of Dynamic Position Changes on Adenoma Detection During Colonoscope Withdrawal: A Randomized Controlled Multicenter Trial.

OBJECTIVES: Adequate luminal distension is essential for improving adenoma detection during colonoscope withdrawal. A few crossover studies have reported that dynamic position changes maximize luminal distension and increase adenoma detection rates (ADR). We designed a multicenter, randomized, parallel-group trial to verify the effect of dynamic position changes on colonic adenoma detection. METHODS: This study was conducted at the six hospitals of the Catholic University of Korea. Patients aged 45-80 years who underwent a colonoscopy for the first time were included. In the position change group, the position changes during colonoscope withdrawal were as follows: cecum, ascending colon, and hepatic flexure: left lateral position; transverse colon: supine position; splenic flexure, descending colon, sigmoid colon, and rectum: right lateral position. In the control group, the examinations were performed entirely in the left lateral position during colonoscope withdrawal. The primary outcome measure was the ADR, which was defined as the proportion of patients with ≥1 adenoma. RESULTS: A total of 1,072 patients were randomized into the position change group (536 patients) or the control group (536 patients). The ADR was higher in the position change group than in the control group (42.4 vs. 33.0%, P=0.002). More adenomas were detected per subject in the position change group (0.90 vs. 0.67, P=0.01). Increases in the number of adenomas were observed in examinations of the transverse colon (0.22 vs. 0.13, P=0.016) and the left colon (0.37 vs. 0.27, P=0.045). A significant increase in the ADR was observed for endoscopists with a relatively low detection rate. For endoscopists with a high detection rate, non-significant changes in the ADR were observed. CONCLUSIONS: Dynamic position changes during colonoscope withdrawal increased the ADR.