Anastomotic biliary stricture following liver transplantation and management analysis: 15 years of experience at a high-volume transplant center.

INTRODUCTION: The occurrence of anastomotic biliary stricture (BS) remains an essential issue following liver transplantation (LT). The present study aimed to compare our findings regarding the incidence of anastomotic BS to what is known. METHODS: The present study is a single-center, retrospective cohort study of a total number of 717 consecutive patients (426 men and 291 women) who had undergone LT from January 2001 to March 2016. Multivariable Cox regression analysis was conducted to evaluate the risk factors associated with anastomotic BS development. RESULTS: Post-transplant anastomotic BS developed in 70 patients (9.8%). In the Cox multivariate analysis (a stepwise forward conditional method), factors including biliary leak (hazard ratio [HR]: 6.61, 95% confidence interval [CI]: 3.08-17.58, p < 0.001), hepatic artery thrombosis (HR: 2.29, 95% CI: 1.03-5.88; p = 0.003), and acute rejection (HR: 2.18, 95% CI: 1.16-3.37; p = 0.006) were identified as independent risk factors for the development of anastomotic BS. Surgery in 6 cases (66.7%), followed by endoscopic retrograde cholangiopancreatography (ECRP) with a metal stent in 18 cases (62.1%), percutaneous transhepatic biliary drainage in 9 (20.9%), and ERCP with a single plastic stent in 8 (18.2%), had the highest effectiveness rates in the management of BS, respectively. CONCLUSIONS: Risk factors including biliary leak, hepatic artery thrombosis, and acute rejection were independently associated with an anastomotic BS. ERCP with a metal stent may be considered as an effective treatment procedure with a relatively low complication rate in the management of benign post-LT anastomotic BS.

Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia.

BACKGROUND: Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical limb-threatening ischaemia. In a substantial number of individuals with CLI, no effective treatment options other than amputation are available, with around a quarter of these patients requiring a major amputation during the following year. This is the second update of a review first published in 2011. OBJECTIVES: To evaluate the benefits and harms of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for CLI. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 8 November 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention, conventional conservative therapy, or placebo). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were all-cause mortality, pain, and amputation. Our secondary outcomes were angiographic analysis, ankle-brachial index (ABI), pain-free walking distance, side effects and complications. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included four RCTs involving a total of 176 participants with a clinical diagnosis of CLI. Participants were randomised to receive either intramuscular cell implantation of BMMNCs or control. The control arms varied between studies, and included conventional therapy, diluted autologous peripheral blood, and saline. There was no clear evidence of an effect on mortality related to the administration of BMMNCs compared to control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.15 to 6.63; 3 studies, 123 participants; very low-certainty evidence). All trials assessed changes in pain severity, but the trials used different forms of pain assessment tools, so we were unable to pool data. Three studies individually reported that no differences in pain reduction were observed between the BMMNC and control groups. One study reported that reduction in rest pain was greater in the BMMNC group compared to the control group (very low-certainty evidence). All four trials reported the rate of amputation at the end of the study period. We are uncertain if amputations were reduced in the BMMNC group compared to the control group, as a possible small effect (RR 0.52, 95% CI 0.27 to 0.99; 4 studies, 176 participants; very low-certainty evidence) was lost after undertaking sensitivity analysis (RR 0.52, 95% CI 0.19 to 1.39; 2 studies, 89 participants). None of the included studies reported any angiographic analysis. Ankle-brachial index was reported differently by each study, so we were not able to pool the data. Three studies reported no changes between groups, and one study reported greater improvement in ABI (as haemodynamic improvement) in the BMMNC group compared to the control group (very low-certainty evidence). One study reported pain-free walking distance, finding no clear difference between BMMNC and control groups (low-certainty evidence). We pooled the data for side effects reported during the follow-up, and this did not show any clear difference between BMMNC and control groups (RR 2.13, 95% CI 0.50 to 8.97; 4 studies, 176 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the concerns about risk of bias, imprecision, and inconsistency. AUTHORS' CONCLUSIONS: We identified a small number of studies that met our inclusion criteria, and these differed in the controls they used and how they measured important outcomes. Limited data from these trials provide very low- to low-certainty evidence, and we are unable to draw conclusions to support the use of local intramuscular transplantation of BMMNC for improving clinical outcomes in people with CLI. Evidence from larger RCTs is needed in order to provide adequate statistical power to assess the role of this procedure.

An update on treatment options for primary sclerosing cholangitis.

Primary sclerosing cholangitis is a chronic cholestatic liver disease defined by strictures of the biliary tree which could ultimately lead to liver cirrhosis and cholangiocarcinoma. Although the exact underlying etiology of this disorder is not fully understood, the pathology is believed to be caused by immune mediated mechanisms. Growing body of evidence suggests several treatment modalities mainly focusing on the inflammation aspect of this disorder. However, there is still no consensus regarding the best treatment option for these patients. Thus, the present study aimed to review the current treatment options for patients with primary sclerosing cholangitis.

Cholangiocarcinoma: State of the Art.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most frequent primary liver tumor and defined as the heterogeneous group of tumors derived from cells in the biliary tree. METHODS AND RESULTS: Based on the anatomical locations (intrahepatic, perihilar, and distal), there are various approaches to the diagnosis and treatment of CCA. Imaging modalities, staging classifications, understandings around natural behavior of CCA, and therapeutic strategies have had remarkable progress in recent years. CONCLUSIONS: This article reviews and discusses the epidemiology, clinical presentation, diagnosis, and treatment modalities of CCA; determines the appropriate inclusion and exclusion criteria for liver transplantation (LT); and defines the risk of disease progression for patients in the waiting list of LT.

Factors Associated With Length of Hospital Stay Following Liver Transplant Surgery.

OBJECTIVES: Length of stay is considered an important surrogate for transplant survival rate and resource utilization. Therefore, in the present study, our aim was to determine factors affecting length of hospital stay. MATERIALS AND METHODS: We retrospectively analyzed records of patients who underwent liver transplant at the Tehran University of Medical Sciences Liver Transplantation Center from March 2014 to March 2016. RESULTS: For our final analyses, there were 161 adult recipients, including 106 males (65.8%) and 55 females (34.1%). Univariate analyses showed that body mass index, Modelfor End-Stage Liver Disease score, duration of surgery, number of administered packed red blood cells and fibrinogen during surgery, reoperation, retransplant, bacterial infection, pleural effusion, ascites, renal failure that required dialysis, and wound infection were risk factors for length of hospital stay. After multivariate linear regression analysis, only body mass index (ß = 0.016; P = .028), Model for End-Stage Liver Disease score (ß = 0.017; P = .002), surgical duration (ß = 0.002; P = .001), reoperation (ß = 0.016; P < .001), presence of pleural effusion (ß = 0.212; P = .042), and management of bacterial infection (ß = 0.21; P = .03) and psychiatric problems after liver transplant (ß = 0.213; P = .025) were independent risk factors for length of hospital stay. CONCLUSIONS: The present study showed that multiple preoperative, intraoperative, and postoperative variables could have an impact on length of hospitalization. Therefore, methods for assessing these factors could improve patient outcomes and resource savings in liver transplant centers.

Comprehensive assessment of respiratory complications in patients with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by recurrent upper and lower respiratory tract infections and some noninfectious clinical complications. OBJECTIVE: To provide a detailed evaluation of respiratory presentations and complications in a cohort of Iranian patients with CVID. METHODS: A retrospective cohort study was conducted on 245 CVID patients who were recorded in the Iranian primary immunodeficiency disorders registry network. Respiratory manifestations were evaluated by reviewing clinical hospital records, immunologic findings, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. RESULTS: Most of the patients (n = 208, 85.2%) had experienced at least 1 episode of acute respiratory manifestation, and pneumonia was observed in 31.6 % (n = 77) of cases as a first disease manifestation. During the follow-up, pneumonia, sinusitis, and otitis media were documented in 166 (68.6%), 125 (51.2%), and 103 (42.6%) cases, respectively. Abnormal PFT measurements were documented in 53.8% of patients. Among these patients, 21.5% showed restrictive changes, whereas 18.4% of patients showed an obstructive pattern. Bronchiectasis was the most frequent radiological finding, confirmed in 27.2% of patients. Patients with bronchiectasis were older at the time of immunodeficiency diagnosis (P < .001) and had longer diagnosis delay (P < .001) when compared with patients without bronchiectasis. CONCLUSION: This study highlights the importance of monitoring the respiratory tract system even in asymptomatic patients. Pulmonary function tests and CT scans are the most commonly used techniques aiming to identify these patients early, aiming to reduce the rate of long-term respiratory complications.

The Role of Melatonin in Colorectal Cancer.

The prevalence and mortality rate of colorectal cancer have been dramatically rising globally. Currently, colorectal cancer is emerging as the fourth leading cause of death and the third most common malignancy worldwide. The major drawback in colorectal cancer treatment is related to severe adverse events of both chemotherapy and radiation therapy that lead to toxicity and inflammation. Recently, melatonin as an antioxidant, immune-stimulant, and antimutagenic agent has been noticed. Different studies worked on the molecular role of melatonin on carcinogenesis progression. Overall, the anticancer activity of melatonin, combined with its actions via multiple signaling pathways, is considered hugely exciting to use this drug as a possible treatment strategy to cure cancer. Apart from its anticancer potential, this drug has shown to induce modulation of chemotherapy toxicity and improving its therapeutic efficacy. The present review aimed to discuss the possible role of melatonin usage in management of colorectal cancer.

Successful Removal of a Biliary Stent in the Jejunum Using Double-Balloon Enteroscopy.

BACKGROUND: Plastic biliary stent placement has been widely used as a safe approach for the management of hilar neoplasms or the dilation of benign biliary obstruction. Despite the complexity of this procedure, this approach is followed by a few complications. The incidence rate of stent migration is about 10%. In a majority of cases, the migrated stents are retained within the gastrointestinal tract and pass through the intestine with no complication or need for medical intervention. CASE REPORT: In this paper, we described the case of the migrated biliary stent with prolonged abdominal pain, which was removed successfully by using double-balloon. CONCLUSION: In the case of patient with prolonged abdominal pain and previous history of biliary stent placement, migration of stent should be considered as differential diagnosis and Double-Balloon Enteroscopy can be a safe approach in those cases.

Respiratory Complications in Patients with Hyper IgM Syndrome.

PURPOSE: Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome. METHODS: A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. RESULTS: Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%). CONCLUSIONS: Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

Candidiasis associated with very early onset inflammatory bowel disease: First IL10RB deficient case from the National Iranian Registry and review of the literature.

Defects in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) are closely related to very early onset (infantile) inflammatory bowel disease (VEO-IBD). In the present study, we report a novel homozygous null mutation within interleukin-10 receptor B (IL10RB) gene in a child presenting with severe VEO-IBD. In accordance with previous reports, our patient manifested with chronic diarrhea, failure to thrive, intermittent fever and multiple anal ulcers associated with Candidiasis. Homozygous null mutation within IL10RB gene (c.92C > T, p.S31P) affecting the extracellular domain of protein was discovered in this patient. In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease.

Early onset inflammatory bowel disease: manifestations, genetics and diagnosis.

Moazzami B, Moazzami K, Rezaei N. Early onset inflammatory bowel disease: manifestations, genetics and diagnosis. Turk J Pediatr 2019; 61: 637-647. Crohn`s disease and ulcerative colitis are immunologically mediated chronic inflammatory conditions, collectively referred to as inflammatory bowel diseases (IBD). While most studies have described the condition in the adult population, recent evidences suggest that IBD in children may represent an etiologically distinct disease from the adult onset IBD. Since a significant proportion of patients diagnosed with IBD demonstrate their clinical manifestations during childhood, knowledge about the disease progression, severity and diagnosis in this particular patient population is crucial. Therefore, in the present study, the clinical manifestations, recent advancements in the genetics of early onset IBD and the clinical approach to diagnoses of IBD in children are described.

The hyper IgM syndromes: Epidemiology, pathogenesis, clinical manifestations, diagnosis and management.

Hyper Immunoglobulin M syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by low or absent levels of serum IgG, IgA, IgE and normal or increased levels of serum IgM. Various X-linked and autosomal recessive/dominant mutations have been reported as the underlying cause of the disease. Based on the underlying genetic defect, the affected patients present a variety of clinical manifestations including pulmonary and gastrointestinal complications, autoimmune disorders, hematologic abnormalities, lymphoproliferation and malignancies which could be controlled by multiple relevant therapeutic approaches. Herein, the epidemiology, pathogenesis, clinical manifestations, diagnosis, management, prognosis and treatment in patients with HIGM syndrome have been reviewed.

Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia.

BACKGROUND: Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. OBJECTIVES: To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). SELECTION CRITERIA: We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. MAIN RESULTS: Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). AUTHORS' CONCLUSIONS: The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.

Granulocyte colony stimulating factor therapy for acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of death in developed countries, and current treatment modalities have failed to regenerate the dead myocardium resulting from the ischemic damage. Stem cells have the potential to regenerate the damaged myocardium. These cells can be mobilized from the bone marrow by factors such as granulocyte colony stimulating factor (G-CSF). OBJECTIVES: To assess the effects of stem cell mobilization following granulocyte colony stimulating factor therapy in patients with acute myocardial infarction. SEARCH METHODS: We searched CENTRAL (The Cochrane Library Issue 4, 2010), MEDLINE (1950 to November week 3, 2010), EMBASE (1980 to 2010 week 48), BIOSIS Previews (1969 to 30 November 2010), ISI Science Citation Index Expanded (1970 to 4 December 2010) and ISI Conference Proceedings Citation Index - Science (1990 to 4 December 2010). We also checked reference lists of articles. SELECTION CRITERIA: We included randomized controlled trials including participants with a clinical diagnosis of AMI who were randomly allocated to the subcutaneous administration of G-CSF through a daily dose of 2.5, 5 or 10 microgram/kg for four to six days or placebo. No age or other restrictions were applied for the selection of patients. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data regarding the clinical efficacy and adverse outcomes. Disagreements were resolved by the third author. MAIN RESULTS: We included seven trials reported in 30 references in the review (354 participants). In all trials, G-CSF was compared with placebo preparations. Dosage of G-CSF varied among studies, ranging from 2.5 to 10 microgram/kg/day. Regarding overall risk of bias, data regarding the generation of randomization sequence and incomplete outcome data were at a low risk of bias; however, data regarding binding of personnel were not conclusive. The rate of mortality was not different between the two groups (RR 0.64, 95% CI 0.15 to 2.80, P = 0.55). Regarding safety, the limited amount of evidence is inadequate to reach any conclusions regarding the safety of G-CSF therapy. Moreover, the results did not show any beneficial effects of G-CSF in patients with AMI regarding left ventricular function parameters, including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06). It should also be noted that the study was limited since the trials included lacked long enough follow up durations. AUTHORS' CONCLUSIONS: Limited evidence from small trials suggested a lack of benefit of G-CSF therapy in patients with AMI. Since data of the risk of bias regarding blinding of personnel were not conclusive, larger RCTs with appropriate power calculations and longer follow up durations are required in order to address current uncertainties regarding the clinical efficacy and therapy-related adverse events of G-CSF treatment.