Tocilizumab in the management of posttransfusion hyperhemolysis syndrome in sickle cell disease: The experience so far.

BACKGROUND: Posttransfusion hyperhemolysis syndrome is a rare but life-threatening form of delayed hemolytic transfusion reaction with lysis of both transfused and autologous red cells, seen predominantly in patients with sickle cell disease. Macrophage activation is thought to play a major role in its pathophysiology. Standard treatment is with intravenous immunoglobulin and steroids but refractory cases pose a major clinical problem. Tocilizumab is a humanized monoclonal antibody against the IL-6 receptor that can inhibit IL-6 induced macrophage activation. METHODS AND MATERIALS: We describe the case of a 33-year-old woman with sickle cell anemia and posttransfusion hyper hemolysis syndrome refractory to standard therapy, treated with Tocilizumab. We also review all cases reported in the literature where Tocilizumab was used for posttransfusion hyperhemolysis. RESULTS: Treatment with Tocilizumab was well tolerated with no observed adverse events. There was no further drop in Hb after day 2 of treatment with subsequent continuous gradual improvement. Her bilirubin dropped significantly after the first dose and continued to improve, while ferritin and LDH reduced significantly after day 2 of treatment with Tocilizumab and continued to drop thereafter. Like in our case, all other cases in the literature where Tocilizumab was used for posttransfusion hyperhemolysis led to rapid clinical responses and no adverse events. DISCUSSION: Even though the number of cases of posttransfusion hyper hemolysis syndrome treated with Tocilizumab are few, they have all been associated with rapid clinical responses with no observed adverse events suggesting that the role of Tocilizumab in this context needs to be further explored.

Automated Red Cell Exchange in the Management of Sickle Cell Disease.

Red cell transfusion represents one of the cornerstones of the chronic management of sickle cell disease, as well as its acute complications. Automated red cell exchange can rapidly lower the number of circulating sickle erythrocytes, without causing iron overload. Here, we describe our experience, having offered this intervention since 2011. A transient reduction in the platelet count by 61% was observed after the procedure. This was not associated with any haemorrhagic complications. Despite exposure to large volumes of blood, the alloimmunisation rate was only 0.027/100 units of red cells. The absence of any iron loading was confirmed by serial Ferriscans, performed over a number of years. However, patients with advanced chronic kidney disease showed evidence of iron loading due to reduced innate haemopoiesis and were subsequently switched to simple transfusions. A total of 59% of patients were on regular automated red cell exchange with a history of recurrent painful crises. A total of 77% responded clinically, as evidenced by at least a 25% reduction in their emergency hospital attendance for pain management. The clinical response was gradual and increased the longer patients stayed on the program. The earliest sign of clinical response was a reduction in the length of stay when these patients were hospitalised, indicating that a reduction in the severity of crises precedes the reduction in their frequency. Automated red cell exchange also appeared to be beneficial for patients with recurrent leg ulcers and severe, drug resistant stuttering priapism, while patients with pulmonary hypertension showed a dramatic improvement in their symptoms as well as echocardiographic parameters.

Remodelling of specialist services enables safe reduction in hospital admissions of patients with sickle cell disease: Lessons from the COVID-19 pandemic.

Sickle cell disease is characterised by recurrent painful crises often leading to hospitalisation. During the COVID-19 pandemic, it was important to try to reduce the need for hospital admission for these high-risk patients while at the same time ensuring that hospital avoidance did not put them at risk of deterioration from disease-related complications. In the 3-month period between March and May 2020, there was a significant reduction in the number of hospital admissions as well as mean length of stay compared with the mean figures over the same months in the preceding 5 years (2015-19), with an overall reduction in inpatient days of 77%. There were no cases of unsafe hospital avoidance or presentations to hospital that were inappropriately delayed. Frequent telephone communication with patients and provision of ambulatory care were, among others, two very important means of supporting our patient population.

Dedicated Barrett's surveillance sessions managed by trained endoscopists improve dysplasia detection rate.

Background and study aim Barrett's esophagus (BE)-associated dysplasia is an important marker for risk of progression to esophageal adenocarcinoma (EAC) and an indication for endoscopic therapy. However, BE surveillance technique is variable. The aim of this study was to assess the effect of dedicated BE surveillance lists on dysplasia detection rate (DDR). Patients and methods This was a prospective study of patients undergoing BE surveillance at two hospitals - community (UHL) and upper gastrointestinal center (GSTT). Four endoscopists (Group A) were trained in Prague classification, Seattle protocol biopsy technique, and lesion detection prior to performing BE surveillance endoscopies at both sites, with dedicated time slots or lists. The DDR was then compared with historical data from 47 different endoscopists at GSTT and 24 at UHL (Group B) who had undertaken Barrett's surveillance over the preceding 5-year period. Results A total of 729 patients with BE underwent surveillance endoscopy between 2007 and 2012. There was no significant difference in patient age, sex, or length of BE between the two groups. There was a significant difference in detection rate of confirmed indefinite or low grade dysplasia and high grade dysplasia (HGD)/EAC between the two groups: 18 % (26 /142) Group A vs. 8 % (45/587) in Group B (P  < 0.001). Documentation of Prague criteria and adherence to the Seattle protocol was significantly higher in Group A. Conclusion This study demonstrated that a group of trained endoscopists undertaking Barrett's surveillance on dedicated lists had significantly higher DDR than a nonspecialist cohort. These findings support the introduction of dedicated Barrett's surveillance lists.

Predicting what can go wrong at endoscopic ultrasound: a large series experience.

OBJECTIVE: Although prior studies have evaluated complications following endoscopic ultrasound (EUS), data on the incidence of unplanned events at EUS, defined as any deviation from the preprocedure plan, are lacking. The aim of this study was to define the incidence, nature, clinical predictors and implications of unplanned events at EUS. DESIGN: Case control study. SETTING: Tertiary referral centre. PATIENTS: 4624 consecutive patients undergoing EUS during a 6 year period were enrolled. For each patient with an unplanned event, two patients with a successful EUS in the same calendar year were randomly selected as controls. MAIN OUTCOME MEASUREMENTS: Unplanned events occurring prior to, during or after EUS procedures were prospectively recorded in a database. RESULTS: 192/4624 patients had an unplanned event (4.1%). In all, 2.1% had a failed procedure for anatomical reasons, 1.3% because of restlessness despite standard sedation and 0.5% for technical reasons. Adverse events occurred in 0.2%. There was no mortality but 4/6 patients with adverse events had to be admitted to hospital (2/4 operated). Eighty-two per cent of patients with an unplanned event had incomplete examinations, 14% had no procedure performed and 4% had complete procedures. In a multivariate analysis, only Afro-Caribbean patient origin, inpatient procedure and cancer staging procedure were independently related to unplanned events (p<0.05 for all). CONCLUSIONS: Unplanned events at EUS are mainly due to anatomical reasons and restlessness, despite sedation. They commonly result in incomplete examination and are related to Afro-Caribbean origin, inpatient procedure and cancer staging.

Endosonographic staging of lower intestinal malignancy.

The use of EUS in the assessment of rectal pathology is well established. The accurate staging of lower intestinal tumours predicts prognosis and guides the planning of individual patient treatment. Increased experience and the development of high resolution three-dimensional EUS has lead to the greater accuracy of rectal staging with EUS of rectal tumours now considered the gold standard showing T stage accuracy that ranges from 75% to 95%, with N stage accuracy ranging from 65% to 80%. The use of EUS in the staging of colonic pathology, however, is not so well established though advances in miniprobe EUS has improved the assessment of colonic tumours. EUS is also of benefit in the assessment of anal pathology though here, accurate correlation with histology has not been firmly established.

Clinicians' attitudes towards endoscopic ultrasound: a survey of four European countries.

OBJECTIVE: Despite the documented effectiveness of endoscopic ultrasound (EUS) in research studies, data on the utilization of this technology in clinical practice are scarce. The aim of this study was to assess EUS availability and accessibility as well as EUS utilization among clinicians from different European countries. MATERIAL AND METHODS: A direct mail survey was sent to members of the national gastroenterological associations in Sweden, Norway, Greece, and the United Kingdom. RESULTS: Out of 2361 clinicians with valid addresses, 593 (25.1%) responded. Overall, EUS was available to 43% of clinicians within their practice but availability varied from 23% in Greece to 56% in the United Kingdom. More than 50% of respondents evaluating patients with esophageal cancer, rectal cancer, or pancreaticobiliary disorders had utilized EUS during the previous year, but utilization varied considerably among different countries, being more frequent in the United Kingdom. In logistic regression analyses, factors independently related to EUS utilization were mainly EUS availability and accessibility as well as perceived utility of EUS (p <0.05 for all). Respondents considered the lack of trained endosonographers (79%) and high cost (52%) as the main barriers to wider EUS use. CONCLUSIONS: The majority of responding clinicians use EUS but overall utilization varies considerably among different countries. There is considerable variation in EUS service availability and accessibility among countries which, together with perceived usefulness of EUS, is a major determinant of EUS utilization. A shortage of trained endosonographers and the high cost are major barriers to wider EUS use. The findings of this study might help to define policies aimed at development of EUS services.

Cytologic diagnosis of pancreatic endocrine tumors by endoscopic ultrasound-guided fine-needle aspiration: a review.

Precise localization and diagnosis of pancreatic endocrine tumors (PETs) is important, because pancreatic PETs have different clinical and biological behavior and treatment modalities than do exocrine pancreatic tumors. In contrast to the much more common exocrine adenocarcinomas, cytologic studies of PET are relatively rare and many cytopathologists lack experience with the cytomorphologic features of these tumors.During the last 10 yr, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has matured into an accurate, highly sensitive, and cost-effective modality for the preoperative localization of pancreatic PETs. This has resulted in an increased number of PETs first sampled as cytology specimens. This manuscript focuses on the cytomorphologic features most suggestive of pancreatic PETs, differential diagnosis, and diagnostic pitfalls of PETs. The technical development of EUS-guided FNA and the ancillary studies for pancreatic PETs are also reviewed. The data summarized in this review indicate that EUS-FNA is a valuable method in the recognition of pancreatic PETs and in most cases cytopathologists could reach a correct diagnosis of these tumors, including their hormone producing capability on aspirated cytologic material.

A prospective control study of the safety and cellular yield of EUS-guided FNA or Trucut biopsy in patients taking aspirin, nonsteroidal anti-inflammatory drugs, or prophylactic low molecular weight heparin.

BACKGROUND: Although the ASGE recommends that high-risk endoscopic procedures can safely be performed on patients taking aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in standard doses, there is a paucity of data on EUS-FNA per se in this setting. OBJECTIVE: We studied the safety and cellular yield of EUS-FNA and/or Trucut biopsy (TCB) in patients taking aspirin, NSAIDS, or prophylactic low molecular weight heparins (LMWH). DESIGN: Prospective control study. PATIENTS: Consecutive patients undergoing EUS-FNA and/or TCB were recruited over an 18-month period. The usage of aspirin, NSAIDS, or LMWH were recorded and patients who were not taking these medications served as controls. MAIN OUTCOME MEASUREMENTS: The bleeding events (endosonographic findings of extraluminal bleeding, intraluminal bleeding requiring hemostatic procedures, hematemesis, or melena) and cellular yield were compared between patients and controls. RESULTS: Two hundred fourteen patients (8 had repeat procedures) underwent EUS-FNA and/or TCB on 241 lesions. Bleeding events occurred in none (0 of 26), 33.3% (2 of 6), and 3.7% (7 of 190) of the patients in the aspirin/NSAIDS, LMWH, and control groups, respectively (p = 0.023). The mean numbers of FNA passes, applications of suction, bloody specimens, and cellular yield were not significantly different between patients who were or were not receiving medications. No significant difference in bleeding events was noted between the FNA and TCB groups. CONCLUSION: EUS-FNA or TCB is safe in patients taking aspirin or NSAIDS. Consideration should be given to stopping LMWH before the procedure. The cellular yield and blood contamination of the specimen from FNA are similar to those in controls.

Duodenal EUS to identify thickening of the extrahepatic biliary tree wall in primary sclerosing cholangitis.

BACKGROUND: Diagnosing primary sclerosing cholangitis (PSC) is problematic and requires meeting a burden of proof through clinical, biochemical, radiologic, and histological features. Endoscopic ultrasound yields detailed images of the extrahepatic biliary tree, but its value in contributing to the diagnosis of this condition is unknown. OBJECTIVES: To determine the potential for transduodenal EUS to detect common bile duct wall thickening in PSC. DESIGN: A prospective, controlled study with retrospective, blinded data analysis. SETTING: Single tertiary referral center for inflammatory bowel disease and EUS. PATIENTS: Four groups of patients were assessed with radial endosonography: PSC (n = 9); inflammatory bowel disease (IBD) with abnormal liver blood tests (n = 21); choledocholithiasis (n = 15); and normal controls (n = 50). Measurements were made of the common bile duct diameter and wall thickness. INTERVENTIONS: Transduodenal radial EUS of the biliary tree. MAIN OUTCOME MEASUREMENTS: Common bile duct diameter and wall thickness. RESULTS: The mean diameter (SD) of the common bile duct for the PSC, IBD, choledocholithiasis, and normal control groups measured 8.9 mm (2.8), 5.4 mm (1.7), 7.2 mm (2.2), and 5.0 mm (1.9), respectively (PSC and choledocholithiasis groups compared to the IBD group, P < .05 for a single test of hypothesis, but correction for the multiple testing of data removed this significance; normal control group P < .005). Mean ductal wall thickness (SD) was 2.5 mm (0.8) for the PSC group, 0.7 mm (0.4) for the IBD group, 0.8 mm (0.4) for the choledocholithiasis group, and 0.8 mm (0.4) for the normal control group, respectively (PSC group compared to the other 3 groups, P < .005). LIMITATIONS: Assessment of intrahepatic PSC is problematic. CONCLUSION: Thickening (>1.5 mm) of the common bile duct wall is seen in patients with PSC but not in those with apparently uncomplicated IBD or choledocholithiasis. The results of this study suggest that standard endosonography contributes to the imaging and potentially to the diagnosis of PSC.

Metastatic lymph node impostor in pancreatic cystadenocarcinoma.

CONTEXT: Lymph node involvement in pancreatic cancer is a predictor of poor patient long-term survival. The detection of multiple metastatic peri-pancreatic nodes by EUS-FNA may dissuade the surgeon from undertaking a curative pancreatic resection. CASE REPORT: We report an interesting case of a man with chronic lymphocytic leukemia, who presented with the diagnostic problem of a pancreatic solid-cystic lesion and multiple malignant-looking peri-pancreatic lymphadenopathy on EUS. EUS-FNA yielded chronic lymphocytic leukaemia involvement in the peri-pancreatic lymph nodes and a markedly elevated CEA in the cystic fluid. The absence of adenocarcinoma involvement of the lymph nodes prompted surgery on the pancreatic lesion with a curative intent. Pancreatic mucinous cystadenocarcinoma was diagnosed and a sub-total pancreatectomy was performed with clear resection margins. All 30 resected peri-pancreatic lymph nodes showed chronic lymphocytic leukemia involvement only. CONCLUSIONS: This case illustrates that abnormal lymphadenopathy adjacent to a primary pancreatic lesion may not necessarily be due to the latter. Systemic lymphoproliferative disease, as in this case, can masquerade as metastatic adenocarcinoma lymph nodes on EUS. EUS-FNA is useful in diagnosing lymphoproliferative disease.

The substitution of endoscopic ultrasound for endoscopic retrograde cholangio-pancreatography: implications for service development and training.

OBJECTIVES: Choledocholithiasis and other benign conditions of the biliary tree are difficult to define clinically. Endoscopic retrograde cholangio-pancreatography (ERCP) is increasingly being replaced as the investigation of choice by other imaging modalities. The aim of this study was to measure the impact of substituting endoscopic ultrasound (EUS) for ERCP in terms of case throughput and the proportion of therapeutic ERCPs performed. METHODS: Over a 12-month period, cases with a low/medium likelihood for biliary pathology were triaged to EUS rather than ERCP. Data were collected on the proportion of ERCPs performed with diagnostic or therapeutic intent and compared with data from the preceding 12-month period. RESULTS: In the 12 months to April 2001, 518 cases were referred for ERCP; 140 underwent EUS and 378 underwent ERCP. The proportions of diagnostic and therapeutic ERCP were 14% and 86%, respectively. Benign biliary disease represented 33% of all referrals for EUS, and calculi were identified in 6% of these cases. During the preceding year, 637 ERCPs were performed. The proportion of diagnostic (33%) and therapeutic (67%) cases differed from the index year (P < 0.001). CONCLUSIONS: The substitution of EUS for ERCP results in significant quantitative and qualitative change to ERCP practice, which has direct consequences for training and service development.

Efficacy and safety of endoscopic dilation of esophageal strictures in epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa is a rare genetically determined disorder of the stratified squamous epithelium. Patients with the most severe forms develop scarring of the esophagus after ingestion of food. This results in dysphagia, which severely compromises the ability to eat. Maintenance of adequate nutritional intake is a central aim, but the most appropriate method is unknown. METHODS: The results of endoscopic through-the-scope balloon dilation under propofol anesthesia in 53 patients with epidermolysis bullosa and esophageal strictures are reported. RESULTS: Seventy-five percent of patients had a single stricture (range 1 to 6 strictures), most often in the proximal esophagus (median 20 cm from incisors). A total of 182 dilations were performed (median two per patient) over a median follow-up period of 3.5 years. For all but 3 patients, there was an improvement in the dysphagia score. There was a mean increase in weight after the procedure of 2.9 kg: 95% CI[2.0, 3.8]; p<0.001, over a median 29 days. There was no significant post-procedure morbidity. CONCLUSIONS: Endoscopic balloon dilation is a safe and effective treatment for the esophageal strictures of epidermolysis bullosa. In the majority of patients, dilation relieves dysphagia and improves nutritional status.