Real-time and non-invasive acute lung rejection diagnosis using confocal LASER Endomicroscopy in lung transplant recipients: Results from the CELTICS study.

BACKGROUND AND OBJECTIVE: Traditionally, the diagnosis of acute rejection (AR) relies on invasive transbronchial biopsies (TBBs) to obtain histopathological samples. We aimed to evaluate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) as a complementary and non-invasive tool for ACR screening, comparing its results with those obtained from TBBs. METHODS: Between January 2015 and April 2022, we conducted a retrospective study of all lung transplant recipients aged over 18 years at Toulouse University Hospital (France). All patients who underwent bronchoscopies with both TBBs and pCLE imaging were included. Two experienced interpreters (TV and MS) reviewed the pCLE images independently, blinded to all clinical information and pathology results. RESULTS: From 120 procedures in 85 patients, 34 abnormal histological samples were identified. Probe-based confocal laser endomicroscopy revealed significant associations between both alveolar (ALC) and perivascular (PVC) cellularities and abnormal histological samples (p<0.0001 and 0.003 respectively). Alveolar cellularity demonstrated a sensitivity (Se) of 85.3 %, specificity (Spe) of 43 %, positive predictive value (PPV) of 37.2 % and negative predictive value (NPV) of 88.1 %. For PVC, Se was 70.6 %, Spe 80.2 %, PPV 58.5 % and NPV 87.3 %. Intra-interpreter correlation (TV) was 88.3 % for the number of vessels (+/-1), 98.3 % for ALC and 90 % for PVC. Inter-interpreter correlation (TV and MS) was 80 % for vessels (+/-1), 97.5 % for ALC and 83.3 % for PVC. CONCLUSION: Our study demonstrates the feasibility of incorporating pCLE into clinical practice, demonstrating good diagnostic yield and reproducible outcomes in the screening of AR in lung transplant recipients.

European Society of Surgical Oncology's strategy for clinical research: Paving the way for a culture of research in cancer surgery.

As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.

Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study.

BACKGROUND: Mastocytosis is characterized by the accumulation/proliferation of abnormal mast cells. The frequency of isolated cutaneous involvement in adults with mastocytosis has not been fully determined. The main objective of our study was to assess the frequency of isolated cutaneous mastocytosis (CM) in adults with mastocytosis skin lesions. The second objective was to compare the clinical, histological, biological and imaging features in patients with isolated CM and patients with systemic mastocytosis (SM). METHODS: We included all patients with histology-proven mastocytosis skin lesions between January 2009 and December 2017. The mastocytosis diagnosis was made according to the international diagnostic criteria. All data were collected from a dedicated specific case report. RESULTS: Among 160 patients with mastocytosis skin lesions, 25 patients had isolated CM (15.6%), 105 had SM and 30 (18.7%) patients had undetermined mastocytosis. Skin KIT mutation (OR: 51.9, 95% CI: 3.9-678, P = 0.001) and high bone marrow tryptase (OR: 97.4, 95% CI: 10.3-915, P = 0.001) were strong predictors of SM. The prevalence of osteoporosis was higher in the SM population than in the isolated CM population. Moreover, a decrease in bone mineral density over a short period of follow-up (1-2 years) was associated with SM. There were no differences between the two groups regarding the frequency of mast cell activation symptoms, the presentation of skin lesions, the number of mast cells in the dermis and the level of serum tryptase. We propose considering the KIT mutation status and bone marrow tryptase levels to aid the diagnosis of isolated CM in adult mastocytosis patients. CONCLUSION: Only a small minority of adults with mastocytosis skin lesions has isolated cutaneous involvement. In 18.7% of mastocytosis cases, even complete workup does not allow for a precise classification of patients.

Contrast-enhanced intra-operative ultrasound as a clinical decision making tool during surgery for colorectal liver metastases: The ULIIS study.

BACKGROUND: Detecting more colorectal liver metastases (CRLMs) during surgery may help optimise strategy and improve outcomes. Our objective was to determine clinical utility (CU) of contrast-enhanced intra-operative ultrasound (CE-IOUS) using sulphur hexafluoride microbubbles during CRLM surgery. METHOD: A prospective phase II trial performed at two comprehensive cancer research centres. Patients operated for CRLMs were eligible and assessable if intra-operative ultrasound (IOUS) and CE-IOUS had been performed and pathological results were available and/or 3-month imaging. CU was defined as the justified change in planned surgical strategy or procedure using CE-IOUS. RESULTS: Out of the 68 patients enrolled, 54 were eligible and assessable. 43 patients underwent pre-operative chemotherapy. The median number of CRLMs was 2 (range, 1-11). Pre-operative staging was performed using MRI. IOUS allowed identification of 45 new CRLMs in 13 (24.7%) patients. Compared to IOUS, CE-IOUS allowed identification of 10 additional CRLMs in 9 (16.7%) patients. Surgery was altered and justified in 4 patients only, leading to a CU rate of 7.70% (95 CI, [3.2, 18.6]). No missing CRLMs were identified by CE-IOUS. CONCLUSIONS: Although the primary endpoint was not met for one protocol violation, secondary endpoints indicate that CE-IOUS has an intermediate added-value for surgeons treating CRLMs. TRIAL REGISTRATION: NCT01880554 (https://clinicaltrials.gov/).

Ultrasound-guided fine-needle capillary cytology of parotid gland masses coupled with a rapid-on-site evaluation improves results.

OBJECTIVE OF THE STUDY: To test whether a direct-on-site microscopic examination of fresh, unstained puncture slides by the radiologist decreases the rate of false-negative cases on ultrasound-guided fine-needle cytology of parotid gland masses. PATIENTS: Thirty parotid gland masses from 28 patients were punctured under ultrasound guidance. The same group was used as its control group. METHODS: After one or two passes, the material was spread on slides and air-dried (control group, without microscopic examination). For the study group, it was thus analyzed unstained under the microscope. A sample was considered adequate if at least six clusters of parotid cells were found per slide on at least two slides. For the study group, new punctures were obtained and slides prepared until this condition was fulfilled. RESULTS: Of the 30 evaluated masses, 100% benefited from a cytological diagnosis after microscopy. Twenty-four were adequate in the control group, while 30 were adequate in the study group. The maximum number of punctures to obtain an adequate sample was six. On-site direct microscopy significantly increased the number of adequate specimens by 20% (P=0.03, CI [1.63-20%]). CONCLUSION: Direct and systematic examination of slides by a radiologist avoided the risk of false-negative results caused by having insufficient sample material.

Use of fluorescent in-situ hybridisation in salivary gland cytology: A powerful diagnostic tool.

OBJECTIVE: Salivary gland cytology is challenging because it includes a diversity of lesions and a wide spectra of tumours. Recently, it has been reported that many types of salivary gland tumours have specific molecular diagnostic signatures that could be identified by fluorescent in-situ hybridisation (FISH). The aim of the present study was to demonstrate the feasibility and efficiency of FISH on routine cytological salivary gland smears. METHODS: FISH was conducted on 37 cytological salivary gland smears from 34 patients. According to the cytological diagnosis suspected, MECT1/MAML2 gene fusion and rearrangements of PLAG1, MYB, or ETV6 were analysed. The presence and percentages of cells that had gene rearrangements were evaluated. Results were compared with the histological surgical samples, available from 26 patients. RESULTS: The PLAG1 rearrangement was observed in 12/20 (60%) cases of pleomorphic adenoma. MECT1/MAML2 gene fusion was observed in 1:2 mucoepidermoid carcinomas but was not observed in five other tumours (two pleomorphic adenomas, one Warthin's tumour, one mammary analogue secretory carcinoma [MASC] and one cystic tumour). MYB rearrangement was observed in 4/4 adenoid cystic carcinomas. ETV6-gene splitting identified one MASC. CONCLUSION: Overall, FISH had a specificity of 100% and a sensitivity of 66.7%. When FISH and cytological analyses were combined, the overall sensitivity was increased to 93.3%. It can thus be concluded that when the FISH analysis is positive, the extent of surgery could be determined with confidence pre-operatively without needing a diagnosis from a frozen section.

Patient satisfaction regarding outpatient mastectomy in Saint-Nazaire hospital center.

OBJECTIVES: To assess patient satisfaction with outpatient mastectomy and their postoperative quality of life. MATERIALS AND METHODS: A retrospective descriptive study was conducted of patients who had a mastectomy as outpatients at the hospital of Saint-Nazaire between January 2013 and May 2015. Patients were contacted by phone to answer a survey assessing their satisfaction. RESULTS: Out of 16 eligible patients for an outpatient mastectomy, 11 patients were included in our study (4 [25%] had to remain hospitalized after their intervention and one patient could not be contacted). One patient (9%) presented a seroma requiring aspiration. No patients were readmitted. All patients, except one, were satisfied with the overall care. CONCLUSION: The management of outpatient mastectomies seems to be a good option, provided that patients are motivated, properly selected and well-informed prior to surgery.

Immunocytochemical staining for p53 and Ki-67 helps to characterise urothelial cells in urine cytology.

OBJECTIVE: The presence of atypical cells in urine cytology is unsatisfactory for both cytologists and clinicians. The objective of this study was to test whether p53 and Ki-67 immunostaining could improve urothelial carcinoma (UC) detection on urinary cytology. METHODS: A total of 196 urine samples were analysed, 142 from the bladder, 41 from the upper tract and 13 from ileal bladder replacement. Cytology results were expressed as normal (N) (n = 81), atypia cannot exclude low-grade UC (ALG) (n = 25), suspicious for high-grade UC (SHG) (n = 39) and high-grade UC (HG) (n = 51). Actual diagnoses were confirmed by histopathological analysis, cystoscopic examination or follow-up for at least 1 year. Immunocytochemistry performed on CytoSpin™ slides allowed the determination of the percentage of positive cells with p53 and Ki-67. RESULTS: The median percentage values [first to third quartile] of p53 and Ki-67 were 0 [0-5] and 0 [0-1] for N cytology, 5 [0-40] and 2 [1-10] for ALG, 10 [0-30] and 6 [3-25] for SHG, and 30 [10-80] and 20 [10-30] for HG, respectively. Statistically higher values were observed for both tests (P < 0.001) in positive cytologies (ALG, SHG and HG). The optimal cut-offs were 5% for p53 and 3% for Ki-67. The sensitivity and specificity for the detection of all UC were 86.4% and 76.7% for cytology alone, 81.3% and 93.2% for cytology and p53, 75.7% and 88% for cytology and Ki-67, and 68.9% and 97.5% for cytology, p53 and Ki-67, respectively. CONCLUSION: Using p53 and/or Ki-67 in addition to cytology increases the specificity without penalising the sensitivity.

All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth.

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-trans-retinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs in both intestinal and diffuse types of gastric carcinoma.

[Total laparoscopic hysterectomy and same-day discharge: Satisfaction evaluation and feasibility study]. / Prise en charge ambulatoire de l'hystérectomie laparoscopique : évaluation de la faisabilité et de la satisfaction des patientes.

OBJECTIVE: To evaluate the safety and patients' satisfaction after outpatient laparoscopic hysterectomy (LH). METHODS: A retrospective case series of 47 patients discharged home the same day after total LH. Outcomes include the same-day discharge rate, complication and readmission rates, patients' short-term satisfaction and an evaluation of patients' opinion several months later. RESULTS: Among the 47 patients, 42 (89%) were discharged the same day. Five patients remained hospitalized due to postoperative complications (4 patients) and the patient's decision (1 patient). No patient required emergency consultation, readmission or reoperation in the first 72hours after discharge. Six patients (13%) had postoperative complications within the first 3 months after the surgery. Four patients (8%) were readmitted, three of them (6%) had to undergo a second surgery. In the short-term assessment, patients were satisfied with the management in 93% of cases and would recommend it to others, with a median satisfaction rate of 3.8 out of 4. CONCLUSION: Ambulatory laparoscopic hysterectomy is feasible in a well-selected population, with a high level of patients' satisfaction. This management could be an alternative to traditional long hospital stays proposed in France.

[Endovascular therapy in the treatment of acute ischemic stroke: what the cardiologist should know]. / Nouveautés dans la prise en charge de l'infarctus cérébral en 2014: ce que le cardiologue doit savoir.

INTRODUCTION: Interventional cardiology procedures are regularly exposed to ischemic neurological complications. IV fibrinolysis is the only approved treatment in ischemic stroke but is very often contraindicated in these situations. Many techniques of interventional neuroradiology (mechanical thrombectomy) have been developed over the past years and are used to treat these patients. OBSERVATION: We report the case of two patients who were admitted in emergency for ischemic stroke with contraindication to IV fibrinolysis (cardioversion for atrial fibrillation under anticoagulation; 24 hours after carotid surgery). These patients were treated by endovascular thrombectomy procedure. DISCUSSION: After validation of IV fibrinolysis within 4.5 hours after stroke onset, techniques of mechanical thrombectomy have gradually been developed, either as a complementary treatment or as an alternative in the case of CI to fibrinolysis. These endovascular thrombectomy devices currently allow recanalization of proximal cerebral occlusions, which correlates with a favorable clinical prognosis. A review of the literature is provided, along with a discussion about the techniques currently being improved, their advantages and disadvantages and the selection of patients that can benefit from endovascular procedures. CONCLUSION: In the case of a sudden occurrence of a neurological deficit during a cardiovascular procedure, a "thrombolysis alert" should be triggered. This will permit the rapid establishment of a clinico-radiological report for selecting stroke patients eligible for a procedure of recanalization by thrombolysis and/or mechanical thrombectomy.

Liver metastases in close contact to hepatic veins ablated under vascular exclusion.

BACKGROUND: Liver metastases (LM) in close contact to hepatic veins (HV) are a frequent cause of unresectability. Reconstruction of hepatic veins is technically difficult and outcomes are poor. Intra-operative radiofrequency ablation (IRFA) with vascular exclusion (VE) may be a useful approach. METHODS: Out of 358 patients operated for LM, 22 with LM close to a HV treated by IRFA under VE with at least one year of follow-up were included in this retrospective study. Technical success was evaluated at four months by CT scan of the ablated lesion. Complications; local, hepatic and extra-hepatic recurrence rates, and overall survival are reported. RESULTS: The median number of metastases was 4.5 [range: 1-12]. Seventeen patients had bilateral metastases. The median size of ablated lesions was 2 cm [range: 1-5.5]. Seven complications occurred (1 Grade 1, 2 Grade 3b and 4 Grade IVa), with no mortality. No recurrence of ablated lesions was detected at four months or during follow-up. Seventeen patients had new or extra-hepatic lesions. Median overall survival for colorectal patients was 40 months 95%CI[17.5-not reached]. CONCLUSIONS: IRFA plus VE for LM in close contact to a HV is a novel approach, appearing to be a safe and effective technique which can extend the applications of liver metastases surgery.

[Guide for establishing and maintaining procedures for review of contracts between the medical laboratory and clients]. / Guide pour l'établissement et le suivi de contrats entre le laboratoire et ses clients.

The medical laboratory is providing services to the patients and clinicians, is a costumer for providers as manufacturers and partner for tierce parties as well. Contracts have to be established with the clients to define agreements and to ensure that the laboratory is able to meet the requirements of the regulation and of the standards. Contracts with partners involved in the processes shall be formally established (collaborative contract). This article includes different types of contracts to establish and control within a contract review.

[Recommendations for the evaluation and follow-up of the continuous quality improvement]. / Recommandations pour l'évaluation et le suivi de la démarche qualité.

Continual improvement of the quality in a medical laboratory is based on the implementation of tools for systematically evaluate the quality management system and its ability to meet the objectives defined. Monitoring through audit and management review, addressing complaints and nonconformities and performing client satisfaction survey are the key for the continual improvement.

Symptomatic diaphragmatic hernia after pulmonary radiofrequency ablation.

Radiofrequency ablation (RF) is a relatively safe and reliable technique for the treatment of pulmonary metastases that has seen rapidly expanding use. Lesions situated near the diaphragm are difficult to treat by RF due to the risk of thermal injury to the diaphragm. Diaphragmatic perforation with progressive development of a diaphragmatic hernia is a rare but serious complication. Treatment is surgical. We present the first case reported in the literature of intestinal obstruction in a left diaphragmatic hernia that developed following RF treatment of a pulmonary metastasis.

[Post-examination phase: description and management control of the process]. / Description et maîtrise du processus post-analytique en biologie médicale.

This article defines the scope of the post-analytical process. This process transforms the results after quality control review into validated results, interpreted by authorized "medical biologists", reported and communicated to the clinicians and patients. This phase includes the treatment of the samples after analysis, their storage and disposal and records archiving. This phase is a key step of the examination involved often in dysfunctions that could hardly harm the patient. These errors are usually the consequence of failing in the control of organization, lack of communication with the clinicians and defect of adaptation to their needs. Examples of quality indicators are proposed, as well as a model of clinico-biological contract.

[Guidelines for results reports of biological examinations]. / Recommandations concernant la transmission des résultats d'examens de biologie médicale.

This article presents recommendations for results reports after release by authorized person to fulfill the French regulation and ISO 15189 requirements. This document points out who can be authorized to communicate the reports and to whom. The advantages and disadvantages of the different ways to use for results report are discussed, as traceability and confidentiality rules to apply. Particular situations as critical values to report and correction of transmitted erroneous results. A table summarizes the different modalities available to communicate the results of examinations performed by the laboratory.