Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study.

Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results: In univariate analysis, several factors significantly correlated (p<0.05) with PFS and/or OS (T-stage, M-stage, the delay between RT and surgery). A high level of post-treatment FoxP3+ TIL density correlated significantly with a better PFS (p = 0.007). In multivariate analysis, a decrease in the CD8+/FoxP3+ iTILs ratio after preopRT correlated with better PFS and OS (p = 0.049 and p = 0.024, respectively). More particularly, patients with a delta CD8+/FoxP3+ <-3.8 had better PFS and OS. Interestingly, the dose fractionation scheme significantly influenced the CD8+/FoxP3+ ratio after treatment (p = 0.027) with a lower ratio with hypofractionated RT (≥2 Gy). Conclusion: Patients with LARC who had a significant decrease in the CD8+/FoxP3+ ratio after preopRT were more likely to live longer. This ratio needs to be validated prospectively to guide physicians in adjuvant treatment decision-making.

[A new prenatal diagnosis case of frontonasal dysplasia]. / Un nouveau cas de diagnostic anténatal de dysplasie frontonasale.

In a 30-year-old patient, the systematic second trimester fetal ultrasound discovered major facial abnormalities suggesting a frontonasal dysplasia (FND). The fetal karyotype was normal but no additional genetic testing was performed. Fetal MRI found an important hypertelorism and an asymmetric cerebral ventricle, with a partially visualized corpus callosum. After several consultations and interviews, the couple made a formal demand for pregnancy interruption, which was approved. Fetal pathologic examination confirmed the diagnosis of FND with no other major associated malformation. This rare pathology results from a midline facial dysgraphia comprising a hypertelorism, a large nasal base, a large clefted nose tip and, a V-shaped hair implantation on the forehead. It often occurs sporadically, of unknown cause, related to a defect in the embryonic nasal capsule development. Syndromic forms have been described with cerebral lesions and possible intellectual deficiency. Consequently, a long and difficult surgical management is necessary, at the expense of poor aesthetic outcome. Seven cases of prenatally diagnosed FND have been reported in the literature, three of which had 3D ultrasound.

[Anatomical and histological study of the uterosacral ligament: practical surgical consequences]. / Evaluation anatomique et histologique du ligament utérosacré : conséquences pratiques en chirurgie.

OBJECTIVE: To define the vascular and nervous relationships of the uterosacral ligament and to analyze histologically its content for a better description of this structure. MATERIALS AND METHODS: Three fresh fetal cadavers, three embalmed and one fresh adult cadavers were used. The anatomical relationships of the uterosacral ligament were studied by dissecting one fresh fetal pelvis and two embalmed adult pelves. By histological and immunohistological examinations, eight biopsies of the cervical origin of the complexe ligamentaire utérosacral (USLC) were analyzed: four from fresh fetuses, two from a fresh adult cadaver and two from an embalmed adult cadaver. The specimens were stained with haematoxylin eosin safran (HES) coloration, with antinervous cell specific antibodies (PS100) and with antismooth muscle actine antibodies (to visualize vessel walls) before examination under optical microscope. RESULTS: On anatomic examination, the uterosacral ligament was covered by the visceral pelvic fascia. By removing this fascia, the uterosacral ligament appeared to be a condensation of nervous fibers made up of hypogastric and pelvic nerves forming the hypogastric plexus. Histologically, the uterosacral ligament contained connective tissue, nervous fibers, sympathetic nodes, vessels and fatty tissue. No structured ligamentous organization was identified. CONCLUSION: The uterosacral "ligament" is in fact a "ligament complex" integrating connective tissue as well as nervous and vascular elements. Radical wide excisions of the USLC during cancer or endometriosis surgery and uterosacral suspension during pelvic floor reconstructive surgery should be performed with caution in order to preserve pelvic innervation.

[Primary non-Hodgkin lymphoma of the uterine corpus. Case report and review of the literature]. / Lymphome malin non Hodgkinien primitif du corps utérin. A propos d'un cas et revue de la littérature.

We report a case of primary nonHodgkin lymphoma (NHL) of the uterine corpus, diagnosed by endometrial biopsy, in a 60-year-old patient suffering from uterine bleeding. Pathological analysis had concluded to diffuse large B-cell lymphoma. Further staging had not revealed other nodal or extranodal localization (Ann Arbor stage IE) and there were no signs of recurrence during follow-up. Therefore, the diagnostic criteria for true primary NHL of the uterine corpus were met. This localization is extremely rare since only six cases have previously been published. The patient was successfully treated by an immunochemotherapy combining rituximab-CHOP and rituximab-VCAP. After 28 months of follow-up, she is free from the disease. A review of the literature regarding these exceptional tumors is undertaken.

[The case of an acardiac headless twin, review of the literature]. / Un cas de jumeau acardiaque acéphale et revue de la littérature.

INTRODUCTION: Monochorial twin pregnancies are characterized by the presence of vascular connections between the twins. These connections can be at the origin of pathologies such as the transfused/transfuser syndrome or the TRAP syndrome which is defined as the association of a headless, acardiac twin with a healthy twin, which is the subject we will study and then review the literature. THE CLINICAL CASE: The case of an acardiac, headless twin which was not diagnosed during pregnancy and was discovered at birth. DISCUSSION AND CONCLUSION: The TRAP syndrome is a very rare phenomenon. Yet, it is crucial to diagnose it as early as possible during pregnancy so as to offer adequate supervision. It is associated to a high death rate in the healthy twin caused by anemia and heart failure. There are therapeutic means to stop vascular anostomoses between the twins so as to perform a selective feticide.

Improved TRAP-silver staining versus conventional radioactive TRAP assays: quantification of telomerase activity during immortalization and in pathological human endometrium.

OBJECTIVES: To develop a sensitive telomeric repeat amplification protocol (TRAP)-silver staining assay for telomerase activity quantification. DESIGN AND METHODS: TRAP assays were performed by using a TRAPeze telomerase kit with or without [alpha-32P]-dCTP. Amplification products were electrophoresed in polyacrylamide gels and detected by autoradiography or a modified silver staining protocol. Telomerase activity was quantified from radioactive counts or optical density of telomerase products from test extracts and controls. RESULTS: TRAP-silver staining assay was at least as sensitive as radioactive TRAP assay and quantified telomerase activity within linearity from 10 to 3,000 cell equivalents. Both methods quantified a weak telomerase activity in normal endometrial glandular epithelial cells (GEC) and a strong increase in immortalized GEC. In human pathologic endometria (n=24), telomerase activity was correlated with lesion seriousness and distinguished simple hyperplasias from nonhyperplasic or cancerous lesions. CONCLUSIONS: TRAP-silver staining assay is suitable for cell and tissue telomerase activity routine quantification.

[Use of polyester urethane (Neuro-Patch) as a dural substitute. Prospective study of 70 cases]. / Utilisation du polyester urethane (Neuro-Patch) comme substitut dural. Etude prospective sur 70 cas.

Between October 1995 and March 1998, 70 patients were treated with a microporous polyester urethane dura substitute (Neuro-Patch), after brain or spinal surgery. These patients were assessed clinically and radiologicaly 10 days, 6 weeks and 1 year after surgery. Radiological evaluation used CT scan or MRI. All dura substitutes were fixed by continuous suture to the surrounding dura-mater. We studied the handling properties, the incidence of infection and of CSF leakage. Eleven patients underwent craniotomy again. This gave us the opportunity to examine the adhesion to the brain tissue and the integration of the dura substitute. Six sheets underwent histological examination. Our results show good handling properties of the material; 3 infections; 6 out of 9 radiological CSF leakage occurred from infratentorial surgery. During reoperation, no adhesion to the brain tissue or injury to the brain while detaching the dura substitute was noticed. An excellent histological integration was observed: pores of the Neuro-Patch were colonized by fibroblasts synthesizing collagen, and there was no immune or inflammatory reaction, with an actual 4 to 6 years follow-up. A Neuro-Patch can therefore be recommended as a dura substitute to repair spinal or cranial dural defects.

[Value of histologic examination of the interamniotic membrane in the twin placenta for confirmation of chorionicity diagnosis]. / Intérêt de l'examen histologique de la membrane interamniotique du placenta gémellaire pour confirmation du diagnostic de chorionicité.

The interest of twin chorionocity and zygosity diagnosis is unquestioned. Indeed, in many medical situations, the knowledge of zygosity is an important fact for management of twins. Prenatal echographia is not a perfect tool to characterize chorionicity, and so postnatal examination of the placenta is always necessary. But macroscopic examination is also not relevant, and competent midwives can make many mistakes. Considering that biological postnatal diagnosis of twin zygosity is difficult and costly, we believe that microscopic chorionicity confirmation is required for identical twins.

Use of energy color Doppler in visualizing fetal pulmonary vascularization to predict the absence of severe pulmonary hypoplasia.

OBJECTIVE: The aim of our study was to determine if the assessment of pulmonary vascularization by energy color Doppler during ultrasound examination can predict the absence of pulmonary hypoplasia before birth in situations where it is a high risk. METHODS: In a prospective study of 12 pregnancies presenting a risk of pulmonary hypoplasia (5 early and prolonged premature ruptures of the membranes, 1 diaphragmatic hernia, 1 chylothorax, 1 pulmonary sequestration, 1 omphalocele, 1 anamnios and 2 Potter's syndromes) energy color Doppler was used to visualize pulmonary vascularization. RESULTS: In 10 cases where pulmonary vascularization could be visualized, none of the infants had pulmonary hypoplasia. In the 2 cases of Potter's syndrome where pulmonary vascularization was not visualized there was a pulmonary hypoplasia. CONCLUSION: The visualization of fetal pulmonary vascularization with energy color Doppler in situations with a high risk of pulmonary hypoplasia can predict the absence of severe pulmonary hypoplasia.

[Pseudotumor form of hepatic distomatosis: successful treatment with praziquantel]. / Forme pseudo-tumorale de distomatose hépatique: guérison par le praziquantel.

Human Fasciola hepatica infection is usually discovered either early, during the acute (invasive) phase, or in the advanced phase, which is characterized by biliary complications. We report a case of liver distomatosis with nodular intra-hepatic lesions in a 58-year-old woman. Radiological investigations showed 3 nodular lesions in the VII segment, which were difficult to distinguish from liver metastases or liver abscesses. Distomatosis serology was positive with passive hemagglutination. After a 5-day treatment with praziquantel, clinical symptoms resolved quickly while serological tests became negative. Radiological images slowly decreased to a calcified scar at 13 months. No side-effects were noted. Praziquantel, whose efficacy in the common presentations of liver distomatosis has recently been demonstrated, also seems effective and well tolerated in case of nodular intra-hepatic lesions.

Competitive RT-PCR to quantify CFTR mRNA in human endometrium.

Because the down-regulation by progesterone of cystic fibrosis transmembrane conductance regulator (CFTR) expression could be a useful specific marker to define the state of implant receptivity in endometrium, a competitive reverse transcription-polymerase chain reaction (RT-PCR) was developed for quantifying the CFTR mRNA concentration in human endometrial samples. A competitor RNA was constructed with the same sequence as the CFTR sequence except for a 20-nucleotide insertion in the middle. The amplified products were separated by polyacrylamide gel electrophoresis. The ratio of CFTR band areas to competitor band areas provided the basis of quantification. Using this competitive RT-PCR, we measured CFTR mRNA in human endometrial samples taken at different periods of the menstrual cycle, in endometriosis, and in hyperplasia. Results show that the method is suitable for measuring the concentration of CFTR mRNA.

Langer mesomelic dwarfism: ultrasonographic diagnosis of two cases in early mid-trimester.

This is a report on two cases of mesomelic dysplasia Langer type. This is a rare kind of dwarfism which combines severe dwarfism with predominant shortening of the forearms and lower legs and other morphological abnormalities. The diagnosis can be made by ultrasonography in the early second trimester of the pregnancy.

[Ivemark syndrome: 2 case reports]. / Syndrome d'Ivemark: 2 cas.

Ivemark Syndrome is a multiple organ syndrome associated with splenic abnormalities, complex cardiac pathology and an abnormality of the abdominal viscera. The incidence in our department is 1/6000 deliveries and the teratogenic effect seems to occur between the 30th and 40th days of intrauterine life, but the cause is unknown. The principal warning signal is bradycardia. Prenatal diagnosis can be made by ultrasound. The prognosis depends on the degree of malformation of the heart.

[Results of colo-anal anastomosis]. / Résultats de l'anastomose colo-anale.

Fifty five cases of rectal resection with colo-anal anastomosis are reported. There were 51 cases of cancer and 4 cases of large villous adenoma. The mean distance between tumor and anal verge was 6.4 +/- 1.1 cm (2-8). The mean resection margin was 29.1 +/- 14.6 mm (0-60). The resection was macroscopically complete in 45 cases of cancer distributed as follows: Dukes stage A = 14, stage B = 12 and stage C = 19. Nine (16.4%) postoperative complications occurred; among four (7.3%) anastomotic fistulas, three were treated by colostomy prolongation and one by abdomino-perineal resection. Thirteen (28.9%) recurrences occurred, of which three (6.7%) were local recurrences. The actuarial five years survival rates was 63%.

Pallister Killian--mosaic tetrasomy 12 p syndrome. Another prenatally diagnosed case.

A new case of mosaic tetrasomy 12 p (46,XY/47,XY, +i12 p), diagnosed during pregnancy from ultrasonographic signs, is reported. We emphasize the peculiar position of the diaphragmatic hernia in this syndrome. Its presence or absence determines the vital prognosis and the age of diagnosis. The knowledge of its possible association with tetrasomy 12 p can contribute considerably to the neonatal diagnosis by directing the work of the cytogeneticist to tissue cultures which enable him to detect the presence of the tetrasomy.

[Brachial plexus block by infraclavicular approach in children. Value of a nerve stimulator? Apropos of 20 cases]. / Blocs plexiques sous-claviculaires chez l'enfant. Intérêt d'un neurostimulateur? A propos de 20 cas.

This study included 20 children (average 8.5 years) undergoing surgery of the upper limb under brachial plexus block. A method of blocking the brachial plexus using an infraclavicular approach is described. Eighteen brachial plexus block were performed under general anesthesia. No complication was observed. Post-operative analgesia was satisfactory in all cases. In 10 cases a nerve stimulator was used. It is not necessary for the realization of a brachial plexus block, but the punction is easier under general anesthesia with this instrument.

[Epidural anesthesia in pediatrics. Apropos of 30 cases]. / Anesthésie péridurale en pédiatrie. A propos de 30 observations.

Continuous epidural anesthesia was carried out in 30 children aged from 2 months to 15 years (12 are less than 5 years old) and scheduled for long surgical procedure (thoracic, abdominal or urologic procedures). The epidural space was punctured under general anesthesia on a midline approach with a saline filled syringe. The catheter is easily inserted and fixed. 28 are inserted before surgery; 2 at the end of procedure. The local anesthesia used was lidocaine 1% (with 1/200,000 epinephrine) and/or bupivacaine 0.5 alone or mixed; bupivacaine wasn't used for children aged less than 6 months. During surgery, complete sensory blockade was obtained in 26 cases; insufficient analgesia or lateralization of the block in the 2 other cases. Complete muscle paralysis, researched for 17 children, was altered for 11 patients. The insufficient was observed in upper abdominal surgery for which etidocaine was used unless the patient is aged less than 6 months (in this case lidocaine 2% was preferred). As complications, a dural penetration was observed in a child aged 2 months, and an hemodynamic instability for another patient for which 100 ml albumin was used. In the post operative period, the catheter remained in situ from 24 to 48 hours, provide safe and effective analgesia and therefore eased the management of the children.

[Closed-circuit anesthesia in children]. / Anesthésie en circuit fermé chez l'enfant.

The aim of this study is to demonstrate how easy and suitable is the closed system in infants and children. An original circuit, adapted from the Bain-Spoerel system, is used. Its principle is to draw-up the expired gas through a soda lime canister by a pump, whose flow is 14 l.min-1. ("Circuit Bisontin"). For this study, 20 infants and children underwent anesthesia with isoflurane, in spontaneous or mechanical ventilation (with a "bag in the bag" principle ventilator). The lowest body weight was 2.7 kg. The advantages are a minimal dead space and no expenditure of energy during spontaneous ventilation thanks to an internal high flow and the absence of internal one-way valve. Gas monitoring is achieved by a four gas analyser (Capbomac Datex).