Small bowel polyp resection using device-assisted enteroscopy in Peutz-Jeghers Syndrome: Results of a specialised tertiary care centre.

INTRODUCTION: Enteroscopy resection of small bowel polyps in Peutz-Jeghers syndrome has only been described in small case series. Herein, we aimed to assess the efficacy of enteroscopy resection of small bowel polyps within a specialised tertiary care centre and the impact on intraoperative enteroscopy. METHODS: This was an observational single-centre study. All adult Peutz-Jeghers syndrome patients followed in the Predisposition Digestive Ile-de-France network who underwent an endoscopic resection of at least one small bowel polyp ≥ 1 cm by enteroscopy between 2002-2015 were included. Small bowel polyps were detected under a dedicated screening programme by previous capsule endoscopy and/or magnetic resonance enterography, performed every 2-3 years. Complete treatment was defined as the absence of polyps ≥ 1 cm after conventional endoscopic resection. Intraoperative enteroscopy or surgical resection were indicated in incomplete treatments. The overall complete treatment rate including conventional enteroscopy and intraoperative enteroscopy was also considered. RESULTS: Endoscopic resection of 216 small bowel polyps (median: 8.6 per patient, size: 6-60 mm) was performed by 50 enteroscopies in 25 patients (mean age: 36 years, range: 18-71, 56% male) with small bowel polyp ≥ 1 cm. Twenty-three patients (92%) underwent 42 screening capsule endoscopies and 14 (57%) had 23 magnetic resonance enterographies during a median follow-up of 60 months. Complete treatment was achieved in 76%. Intraoperative enteroscopy and surgical resection were performed in four (16%) and two (8%) patients. Intraoperative enteroscopy improved by 16% the complete treatment rate and the overall rate was 92%. The complication rate was 6%. CONCLUSION: This long-term study confirmed the efficacy and safety of endoscopic resection of small bowel polyps in Peutz-Jeghers syndrome. Intraoperative enteroscopy can be a complementary approach in selected cases.

Awake surgery for isolated parenchymal degenerating neurocysticercosis - Case report and focused review of misdiagnosis of neurocysticercosis.

Differential diagnosis of isolated single neurocysticercosis can be difficult, and management is controversial. We report here an original surgical strategy, and review previous studies reporting misdiagnosis, using the PRISMA guidelines. A 24-year-old man was admitted to our hospital for recent memory impairment, hypoesthesia of the right hand, and recurrent focal seizures without loss of consciousness. Brain MRI revealed a single ring-enhancing parenchymal lesion in the left superior postcentral gyrus, with large perilesional edema. Since exhaustive systemic exploration was negative, surgical resection of the lesion was decided on in a multidisciplinary team meeting. To preserve eloquent brain areas, surgery was performed in awake condition. It allowed complete resolution of clinical manifestations. The diagnosis of neurocysticercosis was confirmed on pathology. This case illustrates the utility of awake surgery in degenerating neurocysticercosis in functional areas, and emphasizes the importance of including it in differential diagnosis of cystic ring-enhancing brain lesions.

An Automated Recording Method in Clinical Consultation to Rate the Limp in Lower Limb Osteoarthritis.

For diagnosis and follow up, it is important to be able to quantify limp in an objective, and precise way adapted to daily clinical consultation. The purpose of this exploratory study was to determine if an inertial sensor-based method could provide simple features that correlate with the severity of lower limb osteoarthritis evaluated by the WOMAC index without the use of step detection in the signal processing. Forty-eight patients with lower limb osteoarthritis formed two severity groups separated by the median of the WOMAC index (G1, G2). Twelve asymptomatic age-matched control subjects formed the control group (G0). Subjects were asked to walk straight 10 meters forward and 10 meters back at self-selected walking speeds with inertial measurement units (IMU) (3-D accelerometers, 3-D gyroscopes and 3-D magnetometers) attached on the head, the lower back (L3-L4) and both feet. Sixty parameters corresponding to the mean and the root mean square (RMS) of the recorded signals on the various sensors (head, lower back and feet), in the various axes, in the various frames were computed. Parameters were defined as discriminating when they showed statistical differences between the three groups. In total, four parameters were found discriminating: mean and RMS of the norm of the acceleration in the horizontal plane for contralateral and ipsilateral foot in the doctor's office frame. No discriminating parameter was found on the head or the lower back. No discriminating parameter was found in the sensor linked frames. This study showed that two IMUs placed on both feet and a step detection free signal processing method could be an objective and quantitative complement to the clinical examination of the physician in everyday practice. Our method provides new automatically computed parameters that could be used for the comprehension of lower limb osteoarthritis. It may not only be used in medical consultation to score patients but also to monitor the evolution of their clinical syndrome during and after rehabilitation. Finally, it paves the way for the quantification of gait in other fields such as neurology and for monitoring the gait at a patient's home.

Validation of a live animal model for training in endoscopic hemostasis of upper gastrointestinal bleeding ulcers.

BACKGROUND AND STUDY AIMS: The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis. MATERIALS AND METHODS: Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale). RESULTS: A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques. CONCLUSIONS: The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.

[Contribution and limitations of MIS(®) screwed expanders in the jaws: illustration from clinical cases and comparison of the osseous volume from three-dimensional radiographic pictures]. / Intérêts et limites des expanseurs vissés de MIS(®) aux maxillaires : illustration à partir de cas cliniques et comparaison du volume osseux à partir de clichés radiographiques tridimensionnels.

INTRODUCTION: Implanting on an atrophic maxilla alveolar ridge may require bone augmentation. Screwed expanders may sometimes be used, thus avoiding a more invasive bone graft. It allows bone density to increase and results in alveolar ridge expansion, by using bone elasticity and adaptation, allows the optimization of the available bone volume, with low morbidity. TECHNICAL NOTE: Despite its apparent simple implementation, the technique should be adapted to each type of bone so as to optimize results. We present two clinical cases, use of screwed expanders, their action on the crestal bone, and the limitations of this technique depending on ridge configuration. DISCUSSION: Screwed expanders are non-traumatic easy-to-use tools. They can be inserted like implants because they have a good self-tapping effect. Their use is more secure in narrow spaces; they are more comfortable for the patient than impacted expanders use. They allow increase of cancellous bone density, which improves primary stability in case of low density bone. Bone volume preservation and avoiding bone grafts can shorten the implant treatment procedure and decrease costs for the patient. Unfortunately, this technique does not allow alveolar ridge height increase. If this is required, onlay graft or guided tissue generation are the best alternatives.

The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous polyposis: a prospective randomized placebo-control trial.

AIM: Duodenal adenomas occur in about 90% of patients with familial adenomatous polyposis (FAP) and are the second cause of death of patients who have had a prophylactic proctocolectomy. Studies suggest that biliary acids have a role in the development of duodenal adenomas. The aim of this study was to evaluate the impact of ursodesoxycholic acid (UDCA) on duodenal adenoma formation in patients with FAP. METHOD: A randomized, double-blinded, placebo-controlled study was carried out of 71 patients (20-65 years) who already had a restorative proctocolectomy. Subjects received either 10 mg/kg of UDCA orally per day or a placebo tablet for 24 months. The Spigelman severity score was determined after duodenal axial and lateral view endoscopy at 12 and 24 months. RESULTS: At 2 years 55 patients had completed the entire period of treatment. At the end of the follow-up period, nine (25%) patients in the UDCA group and seven (20%) in the placebo group had a decrease in the Spigelman score (P = 0.6142). Patients receiving UDCA had no side-effects (0%) compared with four (14%) in the placebo group (P = 0.0392). CONCLUSION: UDCA had no effect on the development of duodenal adenomas in FAP patients (NCT: 00134758).

The organotelluride catalyst LAB027 prevents colon cancer growth in the mice.

Organotellurides are newly described redox-catalyst molecules with original pro-oxidative properties. We have investigated the in vitro and in vivo antitumoral effects of the organotelluride catalyst LAB027 in a mouse model of colon cancer and determined its profile of toxicity in vivo. LAB027 induced an overproduction of H(2)O(2) by both human HT29 and murine CT26 colon cancer cell lines in vitro. This oxidative stress was associated with a decrease in proliferation and survival rates of the two cell lines. LAB027 triggered a caspase-independent, ROS-mediated cell death by necrosis associated with mitochondrial damages and autophagy. LAB027 also synergized with the cytotoxic drug oxaliplatin to augment its cytostatic and cytotoxic effects on colon cancer cell lines but not on normal fibroblasts. The opposite effects of LAB027 on tumor and on non-transformed cells were linked to differences in the modulation of reduced glutathione metabolism between the two types of cells. In mice grafted with CT26 tumor cells, LAB027 alone decreased tumor growth compared with untreated mice, and synergized with oxaliplatin to further decrease tumor development compared with mice treated with oxaliplatin alone. LAB027 an organotelluride catalyst compound synergized with oxaliplatin to prevent both in vitro and in vivo colon cancer cell proliferation while decreasing the in vivo toxicity of oxaliplatin. No in vivo adverse effect of LAB027 was observed in this model.

Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort.

BACKGROUND: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). AIMS: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. METHODS: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. RESULTS: Only 54% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the nine participating centres (27% to 70%, P≤0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (48% vs. 69%, P≤0.0001). Independent predictors of colonoscopic surveillance were male gender, UC IBD subtype, longer disease duration, previous history of CRC and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 71%, 27 and 30% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. CONCLUSIONS: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis.

Long-term results of subcutaneous parathyroid grafts in uremic patients.

HYPOTHESIS: Parathyroid glands are normally surrounded (entirely or partially) by fatty tissue. Subcutaneous parathyroid grafts are thus located in a normal environment. Therefore, we postulated that the late results of subcutaneous implantation of parathyroid tissue in uremic patients should be at least as good as those reported for intramuscular grafting. We also challenged the idea that the recurrence rate of renal hyperparathyroidism after surgery depended solely on the type of hyperplasia (diffuse vs nodular) observed in the implanted tissue. DESIGN: A retrospective study of a series of patients without loss to follow-up. SETTING: A university hospital and 9 affiliated dialysis units. PATIENTS AND INTERVENTIONS: Fifty-nine patients (33 women and 26 men) operated on for renal hyperparathyroidism underwent the resection of at least 4 parathyroid glands followed by presternal subcutaneous implantation of parathyroid tissue. They were followed up for 12 to 130 months (median, 38 months). MAIN OUTCOME MEASURES: Failure of treatment, recurrence of disease, and hypoparathyroidism. RESULTS: During the study period, 9 patients had to undergo another operation: 2 (3%) for persistent hyperparathyroidism due to a fifth ectopic gland and 7 (12%) for recurrence of hyperparathyroidism resulting from hypertrophy of the subcutaneous grafts. Four patients received a kidney transplant. The prevalence of hypoparathyroidism (intact parathyroid hormone serum level <1.6 pmol/L with a normal or low serum calcium concentration) was 14% (8 of 59 patients), and the curve representing the distribution of intact parathyroid hormone serum concentrations among operated on patients was shifted to the left when compared with the curve of patients who underwent hemodialysis and who had no indication for parathyroid surgery. In this latter group, the peak of the curve was situated between 1 and 2 times the upper normal limit, while it was in the normal range 12 to 130 months after total parathyroidectomy and subcutaneous parathyroid autotransplantation. No relation was observed between the recurrence rate of the disease and the histological characteristics of the parathyroid grafts. Also, their function was not influenced by the presence or absence of aluminum deposits in bone biopsy specimens that were obtained at the time of cervical exploration. CONCLUSIONS: The late results of total parathyroidectomy and presternal subcutaneous grafting compare favorably with the published data on other surgical techniques proposed for the treatment of renal hyperparathyroidism. The ease with which the hypertrophied grafts are removed when the disease recurs warrants further use of this procedure.

Age-related inhibitory activity of rat bone marrow supernatant on osteoblast proliferation.

Because histomorphometric indices of bone formation (osteoblastic index, tetracyclin-labeled perimeter) are deeply depressed in aged rats, while in vitro proliferation of trabecular bone cells was found increased, we hypothesized that a signal to proliferate, correctly induced by increased strains on scarce bone, could be opposed in vivo by an inhibitor present in the bone marrow extracellular medium. Thus, we tested the effect of bone marrow extracellular fluid (BM supernatant) of rat femoral diaphysis on cultures of primary osteoblasts and osteoblastic cell lines and found that it inhibited bone cell proliferation. In a group of 69 female rats aged 4, 12, and 15/21 months, there was a stepwise increase in the inhibitory activity of the BM supernatant. The double reciprocal plots relating inhibition power of the medium to BM supernatant dilution suggest that we deal with a simple system and that the kinetics of the phenomenon are the same in older and younger animals. Moreover, proliferation inhibition by BM supernatant and trabecular bone surface measured by histomorphometry in the distal femoral metaphysis were inversely correlated. Because the extracellular fluid of bone marrow is also the medium surrounding the osteoblasts and their precursor cells, our results suggest that the bone marrow negatively regulates osteogenic cells and that this inhibition could contribute to the inability of older animals to supply osteoblasts to bone in proportion to the demand. Preliminary biochemical characterization of the inhibitor suggests it to be a protein of 30-40 kDa with an isoelectric point (pI) of about 6.5.

Trabecular bone cell proliferation ex vivo increases with donor age in the rat: it is correlated with the extent of bone loss and not with histomorphometric indices of bone formation.

Morphometric parameters of bone formation are markedly depressed in senescent, 21-month old rats and even in middle-aged, 12-month-old animals when compared with mature, 4-month old adults. However, osteoblast-like cells obtained from the metaphyseal trabeculae of the distal femur of 21-month-old female and male rats proliferate more rapidly in primary and secondary cultures than cells from 4-month-old donors. In females the increase in proliferation is significant for donor ages from 4 to 12 months and from 12 to 21 months. Ex vivo cell proliferation is inversely correlated with trabecular bone volume and bone surface in females and with bone surface in males. The relationships are being maintained in females (not tested in males) when cells are grown in serum-free medium. We interpret age and bone loss-dependent stimulated cell proliferation as the in vitro response to an in vivo signal to proliferate resulting from higher strains on less trabeculae. The absence of response in vivo could result from the local deficiency of factors brought back to the cells by the serum-enriched culture medium, or from proliferation inhibitors developing with age.

Combined liver-kidney transplantation in primary hyperoxaluria type 1. Bone histopathology and oxalate body content.

In three patients with end-stage renal failure due to primary hyperoxaluria type 1, successful combined liver-kidney transplantation enabled us to assess the insoluble oxalate pool, which was compared with the histopathological changes observed in iliac crest biopsy specimens. Good correlation was observed between the histopathological grade of bone oxalosis and the estimated oxalate content of the body. In the end-stage of oxalate bone disease, hyperparathyroidism does not play a significant role in bone resorption, which appears to be the consequence of the granulomatous reaction induced by oxalate deposition. Combined liver-kidney transplantation should be performed long before this stage. Early hepatorenal grafting in uremia secondary to primary hyperoxaluria type 1 would avoid the deleterious clinical consequences of systemic oxalosis and shorten the duration of postransplant hyperoxaluria, which may compromise the course of kidney graft.

BOP: biocompatible osteoconductive polymer: an experimental approach.

BOP (biocompatible osteoconductive polymer) is a material proposed for osteosyntheses and for filling of bone defects in orthopaedics, neurosurgery and stomatology. It is a composite made of a copolymer of N-vinylpyrrolidone and methylmethacrylate, of polyamide-6 fibers and of calcium gluconate. The histological investigation includes the study of 30 intact rabbit femurs instrumented with a BOP rod, as well as the study of organs of the reticuloendothelial system. The currently available results show the absence of toxicity on hematopoietic tissue. Zones of osteoblastic activity surround the rods, coupled with an osteoclastic reaction which may result in the partial fragmentation of the polyamide fibers and its incorporation in the newly formed bone. We also observed the encapsulation of the material. The biomechanical approach investigated the mechanical properties of the material in bending and in shear. The radiological aspects of the investigation consisted of computerized axial tomography of the implanted femurs to measure density at the bone-implant interface.

Radiological and histological improvement of oxalate osteopathy after combined liver-kidney transplantation in primary hyperoxaluria type 1.

A 15-year-old patient with severe bone disease (with bilateral fractures of hips and shoulders) due to primary hyperoxaluria type 1 (PH1) was treated with combined liver-kidney transplantation after a 4-year hemodialysis period. Normalization of excessive oxalate synthesis brought in by the liver graft combined with the slow excretion of skeletal oxalate stores by the renal graft led to progressive improvement of clinical, radiological, and histological evidence of oxalate osteopathy. This allowed bilateral hip replacement 3 years after transplantation, which led to complete physical rehabilitation of the crippled patient. Combined liver-kidney transplantation constitutes the treatment of choice for end-stage renal failure due to PH1, even in the face of severe oxalate bone disease.

Bone blood flow and in vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats.

Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n = 6-8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from sham-operated and ovariectomized animals (n = 10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.

The number of fibroblastic colonies formed from bone marrow is decreased and the in vitro proliferation rate of trabecular bone cells increased in aged rats.

Four- and 21-month old female Sprague-Dawley rats were sacrificed and their tibiae and femurs isolated for histology and initiation of bone marrow and trabecular bone cultures. The bone loss observed in 21-month old rats was associated with a markedly decreased osteoblastic index. The percentages of mineralizing trabecular surfaces were only slightly decreased in aged rats, whereas the percentages of mineralizing endocortical surfaces were strikingly decreased. Diaphyseal femoral marrows from 21-month old rats were less cellular than those from four-month old rats, and developed in culture fewer fibroblast colony forming units (FCFU) and fewer adherent cells with phenotypic characteristics of osteoblast-like cells. Trabecular bone cultures from 21-month old rats produced as many cells as cultures from four-month old rats, whereas the amount of trabeculae put into culture was much less in aged rats. Moreover, the proliferation rate in secondary culture was significantly increased in 21-month old rats. Similar responses to calcitriol were observed in bone marrow and trabecular bone cells from aged and younger mature rats, while cAMP responses to PTH were decreased in cells from aged rats. Our data confirm the age-related decrease in the FCFU efficiency of the bone marrow and show a stimulated proliferation of trabecular bone cultures from 21-month old rats that could be seen either as the result of the inhibition in vivo of the response to a signal to proliferate, or as a rebound response to factors present in the serum-enriched medium and lacking in vivo.

Differential diagnosis between secondary hyperparathyroidism and aluminum intoxication in uremic patients: usefulness of 99mTc-pyrophosphate bone scintigraphy.

Forty-one patients in chronic end-stage renal failure and 4 patients with a functioning kidney transplant presented with spontaneous hypercalcemia or intolerance to vitamin D3 sterols and/or oral calcium supplements. Bone iliac crest biopsy with aluminum staining and Tc-pyrophosphate bone scintigraphy with determination of Fogelman score were performed in all cases. Two patients had aluminum-induced osteomalacia (AL O). Thirty-eight biopsies showed renal osteodystrophy (secondary hyperparathyroidism or various combinations of osteitis fibrosa and osteomalacia): 19 with positive staining for aluminum (RO + AL) and 19 without aluminum deposits (RO). The series also comprised 2 cases of pure osteomalacia (OM), 2 cases of osteoporosis (OP), and 1 case of osteoporosis with aluminum accumulation (OP + AL). Mean Fogelman score in RO patients (9.1 +/- 0.3) was significantly higher than in all other categories (5.9 +/- 0.5 for RO + AL, and scores ranging from 0 to 8 in the last 7 patients, p less than 0.01). Patients with massive aluminum accumulation in bone (greater than 75% of the total trabecular surface) showed no or very low uptake of the isotope by the skeleton. Fogelman scores of 9 or higher were always associated with histological secondary hyperparathyroidism. 99mTc-pyrophosphate bone scintigraphy is helpful to distinguish aluminum intoxication from secondary hyperparathyroidism in uremic patients.

[Acceptability of vaccination against influenza]. / Acceptibilité de la vaccination contre l'influenza.

From 1984 to 1986 the general practitioners of Braine-le-Château (Belgium) have studied the frequency of influenza vaccination in people aged more than 65 years and its results. Without any particular promotion, 17% of patients were vaccinated in 1984. Following an information campaign conducted by general practitioners, the figure was 39% in 1985. The next year the information was completed by posters, editorials in newspapers and lectures organized for groups of retreated people. The number of vaccinated patients reached 41%. This study demonstrates that it is possible in a short time to improve the vaccination protection of elderly people through the action of practitioners convinced of efficacity of the influenza vaccine.