Adult haemophagocytic lymphohistiocytosis: a Review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by hyperimmune response. The mortality is high despite progress being made in the diagnosis and treatment of the disease. AIM: This review aimed to update knowledge on adult HLH pathophysiology, identifiy the numerous causes, and help clinicians make early diagnosis and initiate treatment. DESIGN AND METHODS: Using Embase, we searched relevant articles published from January 1, 2010 to October 31, 2019, with the MESH term « hemophagocytic lymphohistiocytosis; macrophagic activation syndrome, adult ¼. RESULTS: The mean age at presentation is about 50 years, with a male predominance. The most frequent disease associations are haematological diseases, viral or bacterial infections, and autoimmune diseases. The pathophysiologic mechanism is probably the combination of inherited genetic mutations and extrinsic triggers. The mortality rate is 26.5% to 74.8%. H-score is more efficient than HLH-2004 criteria to identify HLH, with diagnostic sensitivity and specificity 90% and 79%, respectively.18F-FDG PET/CT is potentially useful for detecting underlying disease and the extent of secondary HLH. Disease-specific treatment should be given as soon as possible. Treatment with corticosteroids combined or not with etoposide is the mainstay of treatment. Monoclonal antibodies and JAK pathway inhibitors show promise of being effective. CONCLUSION: In adult HLH, infectious diseases, autoimmune disease and malignancy should be suspected so that disease-specific treatment can be given promptly. Treatment with corticosteroids combined or not with etoposide is the mainstay of treatment, but new therapies show promise of being effective.

When a metastatic breast cancer is mimicking a pancreatic cancer: case report and review of the literature.

We report the case of a 51 year-old female who complained of jaundice and weight loss. At the time of presentation, she had been in remission from a stage 2a ductal breast carcinoma for 58 months. The clinical presentation was suggestive of a primary pancreas cancer with liver metastases and retroperitoneal lymph nodes. We performed liver and pancreas biopsies that demonstrate a relapse of her old breast carcinoma with positive hormone receptors and HER2 positive. Conservative treatment by chemotherapy was given with Paclitaxel - Trastuzumab and Pertuzumab. Pancreatic metastases are uncommon. Furthermore, pancreatic metastases from breast cancer are very rare. We performed a review of the literature and found 48 cases of pancreatic metastases from breast cancer. We would like to highlight by this case that when a pancreatic lesion appears, in patients with a past history of cancer, physicians must not forget the possibility of metastases from primary tumor even if the initial stage, of the tumor, is low. However the diagnosis is not always easy. If liver and pancreatic lesions occur simultaneously, the clinical presentation can mimic metastatic primary pancreatic cancer. Therefore performing biopsy is highly recommended for making the correct diagnosis and also for the staging of the disease and the choice of the best treatment according to immunohistochemical analysis.

Prevalence and characteristics of renal artery fibromuscular dysplasia in hypertensive women below 50 years old.

BACKGROUND: Renal fibromuscular dysplasia (FMD) is typically diagnosed in young hypertensive women. The 2014 European FMD Consensus recommended screening in all hypertensive women <30 yo. However, the prevalence of renal FMD in young/middle-aged hypertensive women remains unclear. The aim of this work was to assess the prevalence and characteristics of renal FMD in hypertensive women ≤50 yo. METHODS: We retrospectively included all consecutive women aged ≤50 years referred to our Hypertension Unit from 2014 to 2017 and collected standardized information on patient characteristics and screening modalities. RESULTS: Of 1083 incident hypertensive patients, 157 patients fitted with inclusion criteria. The prevalence of renal FMD varied between 3.2% in the whole sample and 7.5% in patients explored by CTA and/or MRA (n = 67). In the subgroup of patients ≤30 yo (n = 32), the corresponding figures were 3.1% and 5.6%. The yearly prevalence of FMD tended to increase over time, in parallel with increased use of CTA/MRA as a first-line imaging modality. Out of 5 patients with renal FMD, 2 were revascularized and 1 had extra-renal FMD. CONCLUSIONS: The prevalence of renal FMD in young/middle-aged hypertensive women is probably one order of magnitude higher than previously assumed, in the range of 3%-8%, depending on imaging modalities. While the diagnosis of FMD does not influence short-term management in all patients, it may allow close monitoring and prevention of complications of the disease over time. This analysis provides the rationale for a prospective, multicentre study aiming at determining the cost-effectiveness of systematic screening for renal FMD.

Regional citrate anticoagulation and influence of recirculation on ionized calcium levels in the circuit.

Regional citrate anticoagulation is now widely used during continuous renal replacement therapy (CRRT), and especially in patients at risk for hemorrhagic complications. A close monitoring is required to avoid citrate overload, leading to metabolic alkalosis or citrate intoxication causing metabolic acidosis. This case report describes a dysfunction of the regional citrate anticoagulation due to the development of a deep vein thrombosis close to the site of insertion of the venous CRRT catheter. The result was a local recirculation in the circuit with a local citrate overload (acidosis and non-measurable calcium). In the patient's blood samples, the [calciumtotal/Ca2+systemic] ratio remained normal as a proof of local citrate accumulation without systemic effects. Initially, CRRT remained effective, but due to the progressive decrease of serum creatinine and cystatin C clearance, the site of catheter insertion was changed.

A developmental variant of the thyroid cartilage.

Neck sonography is commonly used as the first imaging method for acute and chronic neck pain or swelling. Adequate knowledge of normal sonography findings is needed for optimal patient work-up. Although thyroid cartilage is rarely sonographically analyzed, there are anatomical variants detectable with sonography. These variants should not be confused with pathologies. Our case report is focused on cyst-like lesions of the thyroid cartilage, which are uncommon incidental findings when imaging is performed. The aim of this case report is to illustrate the ultrasound and magnetic resonance imaging appearances of these cyst-like formations. These formations are benign, have no clinical significance and do not require any additional assessment.Neck sonography is commonly used as the first imaging method for acute and chronic neck pain or swelling. Adequate knowledge of normal sonography findings is needed for optimal patient work-up. Although thyroid cartilage is rarely sonographically analyzed, there are anatomical variants detectable with sonography. These variants should not be confused with pathologies. Our case report is focused on cyst-like lesions of the thyroid cartilage, which are uncommon incidental findings when imaging is performed. The aim of this case report is to illustrate the ultrasound and magnetic resonance imaging appearances of these cyst-like formations. These formations are benign, have no clinical significance and do not require any additional assessment.

Mortality in patients with high risk Staphylococcus aureus bacteremia undergoing or not PET-CT: A single center experience.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. Previous studies had shown that PET/CT can be helpfull in the management of SAB, leading to reduction of mortality. Factors associated with increased or reduced mortality are not well known. Our objective was to analyze mortality in high risk SAB patients undergoing PET/CT and to identify factors associated with mortality rate. MATERIALS AND METHODS: We performed a retrospective study and reviewed all cases of high risk adult SAB between 2014 and 2017. We analyzed medical records and mortality at 30 days and 90 days and 1 year. RESULTS: A total of 102 patients were included in whom 48 undergone PET/CT. Metastatic foci was identified in 45.8% of cases (22/48). The overall mortality rate was 31.4% (32/102). The mortality rate was 16.6% (8/48) and 44.4% (24/54) in patients undergoing or not PET/CT respectively (P = 0.002). There was a signicantly difference in mortality rate at 30 days (P = 0.001), 90 days (P = 0.004) and one at 1 year (P = 0.002) between patients undergoing or not PET/CT respectively. In multivariate analysis only 18-FDGPET/CT, kidney failure and bacteremia of unknown origin were the 3 mains factors modifying mortality in patients with high risk SAB. CONCLUSION: In our study mortality rate was reduced in high risk SAB patients undergoing PET/CT. kidney failure and bacteremia of unknown origin were other factors associtated with high mortality. Our study confirm that PET/CT is a usefull tool in the management of SAB.

Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.

An Unusual Case of Ureteral Perforation in Minimally Invasive Pedicle Screw Instrumentation: Case Report and Review of the Literature.

BACKGROUND: Injury of the ureter is a potentially devastating complication most often reported in gynecologic, colorectal, or vascular pelvic surgery or endoscopic procedures for ureteric diseases. We report a rare case of ureteral rupture occurring as a complication of percutaneous pedicle screw placement. CASE DESCRIPTION: A 60-year-old man reported unbearable abdominal pain on the day after right L4-L5 transforaminal intervertebral fusion and percutaneous pedicle screw placement. A computer tomography workup showed contrast media extravasation outside the excretory system consistent with a left ureteral traumatic perforation. The patient underwent left nephrostomy and a double-J stent insertion and subsequently fully recovered. The ureter completely healed, enabling stent removal 5 months later. METHODS: PubMed and EMBASE were screened for ureteral injury caused by posterior lumbar surgery. RESULTS: We found 27 other reports with only 1 other case after minimally invasive transforaminal lumbar interbody. CONCLUSIONS: Complications of minimally invasive pedicle screw placement are often described as dural tear of neurologic impairment. This report shows that unexpected side effects are still possible and spine surgeons should be aware especially when performing minimally invasive procedures, in which, by definition, pedicles are concealed from direct visualization.

Aseptic lung and liver abscesses: a diagnostic challenge.

A 67-year-old man known with systemic sarcoidosis was admitted to the department of internal medicine because of cough and chest pain for several weeks. Thoracic tomodensitometry demonstrated multiple pulmonary nodules. Biopsies revealed features compatible with abscesses. Cultures and serologic tests were negative and the patient was successfully treated with prednisone. Three years later, a thoraco-abdominal tomodensitometry showed a relapse in the lung and also the apparition of similar lesions in the liver. Blood test revealed elevated CRP level at 40 mg/L and mild cholestasis. Biopsies of the liver excluded neoplastic or infectious diseases and showed inflammatory granulation tissue with abscess formation. A diagnosis of sarcoidosis-associated aseptic abscesses syndrome was then made, which was successfully treated with corticosteroids.

Lemierre Syndrome of the Femoral Vein, Related to Fusobacterium necrophorum Abscess of Vastus Lateralis.

BACKGROUND: Lemierre syndrome is an uncommon, potentially lethal disorder combining acute oropharyngeal infection caused by Fusobacterium necrophorum, with jugular vein suppurative thrombosis, complicated by anaerobic sepsis with secondary multiple metastatic abscesses. Optimal treatment outcome with reduced or absence of sequelae can be achieved with early diagnosis. CASE REPORT: We present a clinical case of Fusobacterium necrophorum abscess complicated with femoral vein thrombosis, called atypical localization of Lemierre syndrome. This uncommon disease was diagnosed on the basis of clinical, biological, and imaging tests, with a favorable outcome, after a well-orientated antibiotic and surgical course of therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Since its first description in 1936, Lemierre syndrome has been reported in locations other than its initial oropharyngeal site. Because optimal treatment outcome is dependent on early diagnosis, it is imperative for emergency physicians to be aware of this uncommon disease, because in many instances they are the patient's initial point of contact with medical care.

Ossification of a rectal tumor: an uncommon finding.

The authors report the case of a 29-year-old woman with partially calcified stage cT4N2M0 mucoid adenocarcinoma of the mid-rectum. Concomitant neoadjuvant chemoradiotherapy was administered. Preoperative CT scan and MRI demonstrated stable disease with a marked increase of its mineralized component. Histology confirmed a mucoid adenocarcinoma with ossified matrix. Osteocytes were identified in the tumor. TNM (5th edition) staging was ypT3N2M1. This case illustrates heterotopic ossification of a rectal tumor, a fairly uncommon finding. The mechanism of heterotopic bone formation within gastrointestinal adenocarcinoma has not been fully elucidated. The impact of this particular feature on patient outcome is unknown.

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

OBJECTIVES: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. BACKGROUND: LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. METHODS: Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. RESULTS: Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. CONCLUSIONS: LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett's neoplasia.

BACKGROUND AND STUDY AIMS: The role of endoscopic submucosal dissection (ESD) in Barrett's neoplasia is ill-defined, although it might provide a higher curative resection rate and better histologic assessment than endoscopic mucosal resection (EMR). We aimed to assess efficacy, safety, and long-term results of ESD. PATIENTS AND METHODS: A retrospective analysis was done of 75 consecutive patients with Barrett's esophagus who underwent ESD between January 2007 and February 2014. ESD was performed for visible lesions that were multiple, larger than 15 mm, or poorly lifting, or suspected of submucosal infiltration. The primary end point was the rate of curative resection of carcinoma. RESULTS: Median patient age was 68 years (interquartile range [IQR] 61 - 76), median follow-up was 20 months (IQR 8.5 - 37.5), and median maximum specimen diameter was 52.5 mm (IQR 43 - 71). En bloc resection rate was 90 % (66 /73), and rates of curative resection of carcinoma and high grade dysplasia/carcinoma were 85 % (47 /55) and 64 % (42 /66), respectively. G3 differentiation and invasion to greater than pT1m2 were observed in 25 % (14 /55) and 67 % (37 /55) of patients with adenocarcinoma, respectively. There were 5 early ( < 48 hours) adverse events (2 delayed hemorrhages and 3 perforations), all treated endoscopically. No ESD-specific death occurred. Esophageal strictures developed in 60 % of patients, all treated endoscopically. Additional treatment (median sessions 2 [IQR 2 - 3]) for residual Barrett's esophagus were recommended to 62 % (42 /68). At latest follow-up, complete remission of neoplasia and intestinal metaplasia was found in 92 % (54 /59) and 73 % (43 /59) of patients, respectively. CONCLUSION: ESD appears to be safe and effective, with a high rate of curative resection of carcinoma. ESD should be considered for patients with Barrett's neoplasia at risk of incomplete resection or poor pathologic assessment with conventional EMR.

Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by (111)Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100 × 10(9)/L, response (R) for PC≥30 × 10(9)/L and <100 × 10(9)/L with absence of bleeding, no response (NR) for PC<30 × 10(3)/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1-235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR = 1.025 by one-year increase, 95% CI [1.004-1.047], p = 0.020) and pre-operative PC (HR = 0.112 for > 100 versus <=100, 95% CI [0.025-0.493], p = 0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.

Castrate-resistant prostate cancer with peritoneal metastases treated with docetaxel-based chemotherapy.

INTRODUCTION: To identify the risk factors, characteristics and prognosis of patients treated with docetaxel-based chemotherapy for peritoneal carcinomatosis due to metastatic castrate-resistant prostate cancer (mCRPC). METHODS: We retrospectively reviewed our series of mCRPC patients with peritoneal metastases treated with docetaxel-based chemotherapy between 2004 and 2010. RESULTS: Six patients were identified from our institutions' internal cancer registry. Three out of these patients had been treated with laparoscopic radical prostatectomy (LRP). In addition to peritoneal metastases, other metastatic sites were mainly visceral. Only 1 patient developed bone metastases. Peritoneal carcinomatosis occurred mainly in patients with a high Gleason (= or >6) score since 5 out of our 6 patients had a Gleason score ≥7. All 6 patients were treated with docetaxel-based chemotherapy when they developed castration resistance. Five patients benefitted from chemotherapy according to their PSA or RECIST responses. Median survival from the start of docetaxel was 24.5 months. CONCLUSIONS: Our retrospective analysis suggests that peritoneal carcinomatosis occurs mainly in patients with a high Gleason score. It is also possible that tumor seeding occurs during LRP. Patients with peritoneal carcinomatosis resistant to castration seem to benefit from docetaxel-based chemotherapy.

Exploring limits for data registration in the context of PROCARE, a quality improvement project on rectal cancer.

BACKGROUND: A high burden of registration in the context of quality improvement projects may result in registration fatigue. METHODS: Time required for data collection and registration was measured. Quality of care indicators (QCI) were scored and factors for adjusted benchmarking were identified. The PROCARE data set was compared with 5 other European data sets. RESULTS: Time required for data collection varied per domain while time for registration was more uniform. On average, per item 33 seconds were needed for collection and registration. The number of data to be registered per patient was 48-276, depending on the stage of the disease, resulting in a minimum of 25 minutes and a maximum of 2 hours 4 minutes per patient, follow-up not included. Focusing on 43 clinically relevant QCIs would result in a 50% reduction, using aggregate scores for performance audit in a 71% reduction. The PROCARE data set was larger than comparable European data sets. Linkage of the PROCARE database with administrative databases provided confident data on the patients' survival status, but did not appear to be a practical option for other QCIs. CONCLUSIONS: Limiting the aim to performance audit could significantly reduce the burden of registration. In the context of a quality improvement project, the PROCARE Steering Group concluded that detailed clinical data from all centres are still required, which can be reconsidered in the future. Maintenance of a specific database remains of crucial value. Data collection and registration cannot be based on benevolence but should be compensated for.

Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer?

BACKGROUND: Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen are universally recommended for detecting prostate cancer (PCa) metastases in cancer of all stages. However, this two-step approach has limited sensitivity and specificity. OBJECTIVE: Evaluate the diagnostic accuracy of whole-body MRI (WBMRI) as a one-step screening test for PCa metastases. DESIGN, SETTING, AND PARTICIPANTS: One hundred consecutive PCa patients at high risk for metastases prospectively underwent WBMRI, CT, and BS completed with targeted x-rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the images. MEASUREMENTS: This study compares the diagnostic performance of WBMRI, CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC) receiver operator characteristics. A best valuable comparator (BVC) approach was used to adjudicate final metastatic status in the absence of pathologic evaluation. RESULTS AND LIMITATIONS: Based on the BVC, 68 patients had metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was 86% and 98-100%, respectively (p<0.04), and specificity was 98% and 98-100%, respectively. The first and second WBMRI readers respectively identified bone metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT and WBMRI for detecting enlarged lymph nodes was similar, at 77-82% for both; specificity was 95-96% and 96-98%, respectively. The sensitivity of the combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or enlarged lymph nodes was 84% and 91-94%, respectively (p=0.03-0.10); specificities were 94-97% and 91-96%, respectively. The 95% confidence interval of the difference between the AUC of the worst WBMRI reading and the AUC of any of the BS/TXR plus CT lay within the noninferiority margin of ±10% AUC. CONCLUSIONS: WBMRI outperforms BS/TXR in detecting bone metastases and performs as well as CT for enlarged lymph node evaluation. WBMRI can replace the current multimodality metastatic work-up for the concurrent evaluation of bones and lymph nodes in high-risk PCa patients.