Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Rectal cancer radiotherapy.

We present the updated recommendations of the French society of oncological radiotherapy for rectal cancer radiotherapy. The standard treatment for locally advanced rectal cancer consists in chemoradiotherapy followed by radical surgery with total mesorectal resection and adjuvant chemotherapy according to nodal status. Although this strategy efficiently reduced local recurrences rates below 5% in expert centres, functional sequelae could not be avoided resulting in 20 to 30% morbidity rates. The early introduction of neoadjuvant chemotherapy has proven beneficial in recent trials, in terms of recurrence free and metastasis free survivals. Complete pathological responses were obtained in 15% of tumours treated by chemoradiation, even reaching up to 30% of tumours when neoadjuvant chemotherapy is associated to chemoradiotherapy. These good results question the relevance of systematic radical surgery in good responders. Personalized therapeutic strategies are now possible by improved imaging modalities with circumferential margin assessed by magnetic resonance imaging, by intensity modulated radiotherapy and by refining surgical techniques, and contribute to morbidity reduction. Keeping the same objectives, ongoing trials are now evaluating therapeutic de-escalation strategies, in particular rectal preservation for good responders after neoadjuvant treatment, or radiotherapy omission in selected cases (Greccar 12, Opera, Norad).

[Impact of reconstructive or minimal invasive surgery on the assessment of current definitions of postoperative clinical target volume for head and neck cancers]. / Impact de la chirurgie reconstructrice avec lambeaux et de la chirurgie mini-invasive sur la définition du volume cible anatomoclinique des cancers de la sphère ORL.

Advances in the reconstructive surgery and minimally invasive endonasal endoscopic surgery of head and neck is poorly evaluated in terms of their impact on radiotherapy planning and outcomes. These surgical advances have resulted in reduced morbidity with equivalent or better tumor control. In the absence of a recommendation on how to delineate target volumes in patients with flaps or to consider margins after endoscopic endonasal surgery, radiotherapy practices are inevitably heterogeneous. Efforts are needed to increase the therapeutic index of postoperative radiotherapy in these situations. We analysed the rare existing literature and outlined a preliminary basis for a recommendation. Strengthening of multidisciplinarity to accurately define target volumes in these complex and relatively new situations, and "delineation concertation meetings" between radiologists, surgeons and radiation oncologists could probably contribute to improved outcomes.

[Anal canal cancer: In the era of intensity-modulated radiotherapy, outstanding issues]. / Cancer du canal anal : à l'ère de la radiothérapie conformationnelle avec modulation d'intensité, questions en suspens.

Intensity-modulated radiotherapy makes possible to optimize the irradiation and spare normal tissues. The toxicity remains important with concomitant chemotherapy often associated. The improvement of MRI and PET-CT define more precisely the target volumes, which need a higher dose, but necessitates to respect the rules of contouring. The treatment is uniform whatever the stage but should be individualized based on clinical stage and tumor response. New paradigms concern biology, staging, volumes and doses, fractionation and combined treatments.

[Nipple projection augmentation in breast reconstruction by artificial derm injection]. / Augmentation de la projection du mamelon dans les reconstructions mammaires par injection de derme artificiel.

INTRODUCTION: The reconstruction of the Nipple-Areola Complex (NAC) is the last step and a key part in breast reconstruction. The technique to be used should be chosen as to avoid any complications on previous reconstruction steps. The use of local flaps for NAC reconstruction could be associated with implant exposure especially in the presence of a history of radiation therapy. The pure dermal flap could be indicated for the nipple reconstruction after breast reconstruction by implant after radiotherapy. The limit stay in the nipple hypoprojection. We suggest to assess the increase of the nipple projection, reconstructed by pure dermal flap, by injection of Integra® Flowable Wound Matrix (Integra LifeSciences®, Plainsboro, New jersey). PATIENTS AND METHOD: Nipple projection has been measured among patients enclosed from february to March 2016 reconstructed by pure dermal flap: before, after and also at a 6months term from the injection of Integra® Flowable Wound Matrix. Patient satisfaction and complications have been measured retrospectively. RESULTS: Ten patients with an average of 55years have been enclosed, with an average limit of time of 19months (7 to 33months) between the breast nipple reconstruction by dermal flap and the injection. A volume of 1 to 1.6cc has been injected. A significative increase projection of 2mm at a 6months term has been measured (1.5 to 2.5mm, P<0.01), without complication and a satisfaction rate of 4.5/5. CONCLUSION: The injection of an artificial derm-like Integra® Flowable Wound Matrix seems to be efficient to increase the nipple projection reconstructed by pure dermal flap after a breast reconstruction and moreover, without complications.

[Radiotherapy of rectal carcinoma]. / Radiothérapie des cancers du rectum.

Indications, doses and techniques of conformal radiotherapy for rectal carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

[Head and neck adaptive radiotherapy: A tool for the detection of patients requiring adaptive radiotherapy]. / Radiothérapie adaptative des cancers ORL : un outil permettant d'identifier les patients nécessitant une adaptation de leur traitement.

PURPOSE: The purpose of this work was to implement a simple dosimetric alert tool in a retrospective study for six patients suffering from head and neck cancer to detect when a patient might require an adaptive radiotherapy. MATERIALS AND METHODS: The dosimetric tool generates a 3D cartography of two dosimetric complementary information: a dose variation tolerance map and a dose differential map. The tolerance map is calculated on the initial scanner (CTinit) using the planned dose distribution. It shows for each voxel of each delineated volume the availability for local dose variations during the course of radiotherapy without exceeding the dose threshold. The differential dose map is generated on the tomographic image CBCT (CBCTtreatment). It shows dose variations between the planned and the actual delivered dose distribution for each voxel. By comparing both maps, when a voxel presents a value superior to the corresponding dose variation tolerance, an alert is generated and the anatomical areas concerned are visually indicated to the physician. RESULTS: The application of the dosimetric tool on six patients with head and neck cancers reveals the ability of the tool to detect cases requiring a new treatment plan. Two patients whose the tumour shrinkage produced an increase of the delivered dose to the spinal cord beyond 45 Gy have been detected. CONCLUSION: The development of the dosimetric tool allows the automatic detection, with no delineation needs, of patients suffering from head and neck cancers requiring an adaptive strategy.

[Radiochemotherapy for esophageal cancer: which nodes should be irradiated?]. / Chimioradiothérapie des cancers de l'œsophage : quelles aires ganglionnaires faut-il irradier ?

Esophageal cancer has a high likelihood of distant lymphatic spread even at an early stage. Radiotherapy plays a major role in the management of localized or locally-advanced esophageal cancer with a regional or distant lymph node involvement. Radiotherapy can sterilize micrometastatic nodes and cancer cells in transit in the peri-esophageal fat that are not removed by surgery. After preoperative chemoradiotherapy followed by monobloc esophagectomy including lymph node dissection above and below the diaphragm, the locoregional failure rate was around 3% in the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study Group (CROSS) trial. This is significantly lower than that observed with surgery alone or following exclusive chemoradiotherapy delivering 50 Gy over 5 weeks. Patterns of failure usually combine local and nodal failure. These results suggest that: (1) radiotherapy plays a major role in the management of micrometastatic nodes that are not removed by surgery; (2) the total dose of radiotherapy without surgery may be too low to control macroscopic disease. Better knowledge of regional failure sites and the enhancement of clinical practices through homogenized nodal radiotherapy could lead to a decrease in regional relapses, but at the expense of irradiated volumes greater than the macroscopic tumor volume. Intensity-modulated radiotherapy or volumetric modulated arctherapy makes it possible to increase mediastinal irradiated volumes while effectively protecting healthy tissues.

Penetration of daptomycin into bone and synovial fluid in joint replacement.

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.

[Reirradiations of head and neck cancers: state of the concept and ways of development]. / Ré-irradiations des cancers de la tête et du cou : état du concept et voies de développement.

The treatment of local recurrence or second primary developed in irradiated area in the field of head and neck carcinoma, should be planned and organized through multidisciplinary discussions. The outcome of such a clinical situations benefits from second line and advanced technology treatments. Only a few patients are amenable to salvage surgery, hence radiation therapy, combined or not with chemotherapy, takes a major role in these indications. This overview of the literature describes recent development in this field, aiming to improve local control while the sparing of organ at risk remains an important goal. Radiation therapy is currently implementing major new technologies set to improve external beam irradiation with new concepts on dose, fractionation, intensity modulated radiation therapy and stereotactic approach - as well as in brachytherapy. Apart from dedicated studies, the great heterogeneity of the treated patients should be underlined and taken into consideration. However, current data confirm the feasibility of reirradiation with acceptable local control and toxicity.

Fixation of distal radius fractures in adults: a review.

In patients for whom function is a priority, anatomic reduction and stable fixation are prerequisites for good outcomes. Several therapeutic options exist, including orthopedic treatment and internal fixation with pins (intra- and extrafocal), external fixation which may or may not bridge the wrist, and different internal fixation techniques with dorsal or palmar plates using or not, locking screws. Arthroscopy may be necessary in case of articular fracture. In the presence of significant metaphyseal bone defects, filling of the comminution with phosphocalcic cements provides better graft stability. The level of evidence is too low to allow recommending one type of fixation for one type of fracture; and different fixation options to achieve stable reduction exist, each with its own specific complications. With the new generations of palmar plate, secondary displacement is becoming a thing of the past.

[Anatomy and biomechanics of distal radius fractures: a literature review]. / Aspects anatomiques et biomécaniques des fractures du radius distal de l'adulte : revue de la littérature.

Distal radius fractures remain the most frequent fractures in the adult. Associated osteoporosis increases morbidity risk (secondary displacement is the most frequent) and mortality risk (in women older than 60). Severity of the fracture and functional results are related to the bone mineral density. Anatomy has been recently revisited with better description of palmar and dorsal aspects in order to avoid material-related complications. Standard postero-anterior, lateral and oblique radiographs of the wrist show the fracture and the displacement. CT scan is warranted if conventional X-rays are insufficient to show the articular surface. The involvement of the metaphysis (comminution), the epiphysis (articular fracture) and the ulna is different in each case and each fracture is an association of these three components. The MEU classification describes the fracture with sufficient inter-observer reliability and intra-observer reproducibility to be a useful tool for treatment and prognosis. The PAF system is used to propose the most appropriate treatment for each patient. Anatomical reduction and stable fixation are associated with good functional results but in high demanding patients.

Fixation of split anterior tibialis tendon transfer by anchorage to the base of the 5th metatarsal bone.

Split anterior tibialis transfer is a procedure, frequently performed in combination with triceps surae lengthening, to treat equinovarus foot deformity in adult hemiplegia patients. The authors present their surgical technique, with tendon fixation by an anchor to the base of the fifth metatarsal. Although bone-tendon anchor fixation is widespread in orthopedic surgery, it is original in this type of indication. It is simpler, and less traumatic for the bone than a bone tunnel and less traumatic for the sole than transplantar fixation. The very distal attachment to the base of the 5th metatarsal bone solves the common problem of adjusting the tension of tendon transfer. The authors report their experience of 22 split transfers from 2005 to 2008.

[Distal radius fracture with dorsal displacement: correlation between functional score, reduction quality and fixation]. / Fractures du radius distal à déplacement dorsal: corrélation entre scores fonctionnels, qualité de réduction et type de fixation.

Appropriate treatment for fractures of the distal radius with dorsal displacement remains a subject of debate. Intrafocal pinning is the most widely used technique in France. Plate fixation has been developed to avoid secondary displacement and stiffness sometimes observed after pinning. We compared three osteosynthesis techniques for the same type of fracture (extra-articular with dorsal displacement). Sixty-two consecutive patients underwent osteosynthesis using the following techniques successively: posterior plates (20 patients mean age 59.9 years [range 25-87 years]), intra- and extrafocal pinning (22 patients mean age 55.6 years [range 17-83 years]), the anterior plate (20 patients mean age 57.1 years [range 17-78 years]). An independent operator evaluated all patients using the Herzberg, Gartland and Werley and Dash scores. The radial slope in the frontal plane, sagittal tilt, and ulnar variance were measured and compared between the preoperative and last follow-up values. Kruskall-Wallis or ANOVA were applied as appropriate for continuous variables and the Chi-square test for non-continuous variables. P<0.05 was considered significant. Mean operative time was equivalent for the two plates fixation techniques and twice as long as for pinning. There were more complications in the posterior plating group (32%) and less satisfactory function score despite a two-fold longer follow-up and a smaller number of operators. The best results were obtained with the anterior plating group in terms of range of motion (flexion-extension), DASH score, preservation of ulnar variance and presence of a largest number of excellent and very good outcomes according to Gartland. The pinning group provided the best results in terms of sagittal slope. The pinning and anterior plating groups had equivalent range of motion for pronation-supination and the same rate of complications (5%). Irrespective of the treatment arm, the Herzberg scores and the Gartland and Dash scores were better: in men, in patients aged less than 30 years, in patients with an associated fracture of the apex of the ulnar syloid process rather than its base. For these extra-articular fractures, pinning can provide good functional results like anterior plating but each treatment has advantages that functional analysis detected.

Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience.

BACKGROUND: Adalimumab may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis who had secondary failure to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab in patients with ulcerative colitis who previously responded to infliximab, and then lost response or became intolerant. METHODS: We report our single-centre experience in 13 patients. The patients received a loading dose of 160 mg of adalimumab subcutaneously in week 0, followed by 80 mg at week 2 and then 40 mg every other week starting at week 4. The primary efficacy measure was the proportion of patients on adalimumab therapy during the study. RESULTS: Median duration of follow-up was 42 weeks (range, 10-100). The mean number of adalimumab infusions was 21 (range, 5-50). The probability of maintaining adalimumab was 92.3%, 84.6%, 60.6% and 32.5% at 1, 3, 6 and 23 months respectively. Six of 13 patients (46.2%) underwent colectomy during the study. No serious toxicities occurred in the study. CONCLUSION: Adalimumab is well-tolerated and may be effective in maintaining clinical remission in a subgroup of patients with ulcerative colitis and lost response or intolerance to infliximab, potentially avoiding colectomy in about half of the patients.

[Helminths and inflammatory bowel diseases]. / Helminthes et maladies inflammatoires chroniques intestinales.

The current etiologic model of inflammatory bowel diseases proposes a genetically predisposed host responding to a variety of environmental triggers by exhibiting an abnormal immune response to normal luminal flora. Crohn's disease is common in highly industrialized western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. From this observation grew the hygiene hypothesis, which states that our failure to be exposed to previously common infectious agents alters the immune repertoire established in childhood. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Crohn's disease involves over reactive T-helper (Th1) pathways, and helminths blunt Th1 responses, inducing production of Th2 cytokines. Helminths also induce regulatory T cells to maintain host mucosal homeostasis. Thus, there is an immunological basis to expect that exposure to helminths such as Trichuris suis will prove beneficial in Crohn's disease. Exposure to helminths may be effective in treating inflammatory bowel diseases and was well tolerated, according to the results of few studies. Its long-term safety remains unknown.

[Small cell lung cancer (CPC). Small cell bronchial carcinoma: therapeutic management]. / Les cancers à petites cellules (CPC). Prise en charge thérapeutique.

Small cell bronchial carcinoma holds a prominent position among malignant tumours on account of its high incidence and the problems of its treatment. The diagnostic approach is dictated by the concern not to overlook any metastatic sites. Small cell bronchial carcinoma is often metastatic at the time of diagnosis and should be considered an actual or potential systemic disease. Chemotherapy is therefore the basis of treatment. It should consist of at least a two drug regime combining cisplatin and etoposide. In extensive disease, that is when all the disease cannot be contained within one irradiation field, chemotherapy alone is recommended. In limited disease combined simultaneous radiotherapy and chemotherapy is recommended. Prophylactic cranial irradiation is indicated in patients in complete remission after chemotherapy. The therapeutic armamentarium has recently been enlarged by the development of new antineoplastic drugs and the development of non-toxic targeted agents including those influencing angiogenesis. The understanding of the specific mechanisms of drug resistance and the study of the tumour phenotypes and genotypes will allow, in the future, the development of treatments adapted for each patient.

[Concomitant use of radiotherapy and gemcitabine: preclinical findings and clinical practice]. / Association concomitante de la radiothérapie et de la gemcitabine: données précliniques et études cliniques.

Gemcitabine is pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors. Laboratory studies demonstrating that gemcitabine is a potent radiosensitizer led to a variety of trials combining radiation and gemcitabine. In the clinic, phase I-II studies are still trying to determine the optimal dose and schedule which could be use in daily clinical practice. This review summarizes the mechanisms of interaction between radiotherapy and gemcitabine and presents several therapeutic schemes for each tumor location.