Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis.

BACKGROUND: Proteasomes are the main non-lysosomal proteolytic structures which regulate crucial cellular processes. Circulating proteasome levels can be measured using an ELISA test and can be considered as a tumour marker in several types of malignancy. Given that there is no sensitive marker of hepatocellular carcinoma (HCC) in patients with cirrhosis, we measured plasma proteasome levels in 83 patients with cirrhosis (33 without HCC, 50 with HCC) and 40 controls. METHODS AND RESULTS: Patients with HCC were sub-classified into three groups according to tumour mass. alpha-Fetoprotein (AFP) was also measured. Plasma proteasome levels were significantly higher in patients with HCC compared to controls (4841 (SEM 613) ng/ml vs 2534 (SEM 187) ng/ml; p<0.001) and compared to patients with cirrhosis without HCC (2077 (SEM 112) ng/ml; p<0.001). This difference remained significant when the subgroup of patients with low tumour mass (proteasome level 3970 (SEM 310) ng/ml, p<0.001) was compared to controls and patients with cirrhosis without HCC. Plasma proteasome levels were independent of the cause of cirrhosis and were weakly correlated with AFP levels. With a cut-off of 2900 ng/ml, diagnostic specificity for HCC was 97% with a sensitivity of 72%, better than results obtained with AFP. Diagnostic relevance of plasma proteasome measurement was also effective in low tumour mass patients (sensitivity 76.2% vs 57.1% for AFP). CONCLUSION: The plasma proteasome level is a reliable marker of malignant transformation in patients with cirrhosis, even when there is a low tumour mass.

Impact of Intragastric Balloon Before Laparoscopic Gastric Bypass on Patients with Super Obesity: a Randomized Multicenter Study.

BACKGROUND: Super obese patients are recommended to lose weight before bariatric surgery. The effect of intragastric balloon (IGB)-induced weight loss before laparoscopic gastric bypass (LGBP) has not been reported. The aim of this prospective randomized multicenter study was to compare the impact of preoperative 6-month IGB with standard medical care (SMC) in LGBP patients. METHODS: Patients with BMI >45 kg/m2 selected for LGBP were included and randomized to receive either SMC or IGB. After 6 months (M6), the IGB was removed and LGBP was performed in both groups. Postoperative follow-up period was 6 months (M12). The primary endpoint was the proportion of patients requiring ICU stay >24 h; secondary criteria were weight changes, operative time, hospitalization stay, and perioperative complications. RESULTS: Only 115 patients were included (BMI 54.3 ± 8.7 kg/m2), of which 55 underwent IGB insertion. The proportion of patients who stayed in ICU >24 h was similar in both groups (P = 0.87). At M6, weight loss was significantly greater in the IGB group than in the SMC group (P < 0.0001). Three severe complications occurred during IGB removal. Mean operative time for LGBP was similar in both groups (P = 0.49). Five patients had 1 or more surgical complications, all in the IGB group (P = 0.02). Both groups had similar hospitalization stay (P = 0.59) and weight loss at M12 (P = 0.31). CONCLUSION: IGB insertion before LGBP induced weight loss but did not improve the perioperative outcomes or affect postoperative weight loss.

Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic analysis for gastro-oesophageal reflux assessment.

Oesophageal pH-impedance monitoring allows detection of acid and non-acid gastro-oesophageal reflux (GOR) events. Visual analysis of impedance recording requires expertise. Our aim was to evaluate the efficacy of an automated analysis for GOR assessment. Seventy-three patients with suspected GORD underwent 24-h oesophageal pH-impedance monitoring. Recordings analysis was performed visually (V) and automatically using Autoscan function (AS) of Bioview software. A symptom index (SI) > or =50% was considered for a significant association between symptoms and reflux events. AS analysis detected more reflux events, especially non-acid, liquid, pure gas and proximal events. Detection of oesophageal acid exposure and acid reflux events was similar with both analyses. Agreement between V and AS analysis was good (Kendall's coefficient W > 0.750, P < 0.01) for all parameters. During pH-impedance studies, 65 patients reported symptoms. As compared to visual analysis, the sensitivity and specificity of a positive SI determined by AS were respectively 85.7% and 80% for all reflux events, 100% and 98% for acid reflux and 33% and 87.5% for non-acid reflux. Despite good agreement with visual analysis, automatic analysis overestimates the number of non-acid reflux events. Visual analysis remains the gold standard to detect an association between symptoms and non-acid reflux events.

Normal values and day-to-day variability of 24-h ambulatory oesophageal impedance-pH monitoring in a Belgian-French cohort of healthy subjects.

BACKGROUND: Impedance-pH monitoring is the most sensitive method for detection and characterization of gastro-oesophageal reflux episodes. Normal values from European subjects are lacking. AIM: To build a database of gastro-oesophageal reflux patterns from French and Belgian healthy subjects. METHODS: Seventy-two healthy subjects (35 men, mean age 35 years, 18-72) underwent 24-h ambulatory impedance-pH studies. Gastro-oesophageal reflux episodes were detected using impedance and characterized by pH as acid, weakly acidic, or weakly alkaline. Analysis was performed visually and effects of age, gender and intra-individual reproducibility were evaluated. RESULTS: The total number of gastro-oesophageal reflux episodes was 44 (25,58,75) of which 59% were acid, 28% were weakly acidic and 10% weakly alkaline. Half of gastro-oesophageal reflux episodes were mixed (liquid/gas) and 22% reached 15 cm above the lower oesophageal sphincter. The bolus clearance time was 11 s while acid was chemically cleared in 34 s. Male gender was associated with increased number and proximal extent of total and acid gastro-oesophageal reflux. Repeated studies in 27 subjects showed good reproducibility for number, acidity and air-liquid composition of reflux (Kendall's W-values = 0.72-0.85). CONCLUSIONS: This study demonstrates good reproducibility of 24-h ambulatory impedance-pH studies and provides values of reflux patterns in healthy subjects for comparisons with European gastro-oesophageal reflux disease patients.

A comparative study of cisapride and ranitidine at controlling oesophageal acid exposure in erosive oesophagitis.

BACKGROUND: The severity of gastro-oesophageal reflux disease is generally considered to be related to the extent of oesophageal acid exposure. Current therapies include antisecretory and prokinetic agents. We compared two of these, ranitidine and cisapride, in their ability to lower oesophageal acid exposure in patients with erosive oesophagitis. METHODS: Seven patients with Savary-Miller's grade II-IV oesophagitis and with oesophageal contact time > or = 8% were studied. Mean lower oesophageal sphincter pressure was 4.6 mmHg. Oesophageal acid contact time was 25.6 +/- 5.6%. Each patient received ranitidine 150 mg b.d., ranitidine 150 mg q.d.s., or cisapride 10 mg q.d.s. in a randomized 3-way cross-over design. Intra-oesophageal pH was monitored during 24 h for each of these treatments in a controlled hospital environment, while consuming a high fat, high calorie diet. RESULTS: Cisapride and ranitidine at both doses decreased the acid contact time and the number of reflux episodes. However, a minority of patients treated with ranitidine, and none with cisapride, diminished their oesophageal acid contact time to a normal value of < 5%. No treatment significantly decreased nocturnal acid exposure. CONCLUSION: In patients with severe gastro-oesophageal reflux disease both cisapride and ranitidine demonstrably lower oesophageal acid exposure, but neither therapy predictably normalizes it.

Sham feeding disrupts phase III of the duodenal migrating motor complex in humans.

The role of the vagus nerve in the control of the intestinal migrating motor complex (MMC) is unclear. This study aimed to evaluate the effect of physiological vagal stimulation with sham feeding on phase III of the MMC. Antroduodenal motility was recorded in six healthy volunteers. The first phase III was used as a control, and sham feeding was performed during the second phase III. The MMC was disrupted within 1.5 +/- 0.4 min of sham feeding and its duration was shorter than the control phase III. Phase III propagation was inhibited in all subjects, most of them exhibiting no propagation beyond the third duodenal recording site. During sham feeding, the antrum exhibited transient phasic contractions in five out of six subjects. The duodenal motility index recorded for up to 30 min after the onset of the sham feeding was unchanged in five out of six subjects. We conclude that sham feeding consistently interrupted phase III of the duodenal MMC and induced antral contractions, but failed to provoke significant motor events in the duodenum.

Primary sinusoidal lymphoma of the liver revealed by autoimmune hemolytic anemia.

Primary liver lymphomas usually present with the clinical picture of a liver tumor, and are characterized by a predominantly portal invasion by lymphoid cells of the B-cell phenotype. We report a case of primary sinusoidal lymphoma of the liver, in a 36 year-old male patient, revealed by homogeneous hepatosplenomegaly and infiltration of liver sinusoids by morphologically normal lymphocytes, without destruction of the parenchyma. Immunohistochemistry in paraffin-embedded tissue sections was positive for the pan T-cell marker MTI, weakly positive for UCHLI, and negative for CD3, and B-cell markers were negative; these findings were consistent with the diagnosis of T-cell lymphoma. The clinical, histological and immunological presentation of this lymphoma was similar to that of hepatosplenic gamma delta T-cell lymphoma. Autoimmune hemolytic anaemia preceded the lymphoma. Despite chemotherapy, the patient died 24 months after the initial presentation in the leukemic phase. A better understanding of this exceptional but characteristic entity is required for an accurate and early diagnosis.

[Deglutition disorders in the elderly. Evaluation methods]. / Les troubles de la déglutition du sujet âgé. Procédés d'évaluation.

FROM DISCOVERY TO CLINICAL DIAGNOSIS: Dysphagia is easy to diagnose in its acute stage and when complicating a known neurological disease. However diagnosis may be greatly delayed when expressed by respiratory or nutritional symptoms, or when the patient presents cognitive disorders, as is frequent in the elderly. In such instances, simple tests such as the water test are clearly indicated. However, although they are reliable for diagnosing dysphagia, they are not precise in diagnosis of inhalation. Clinical examination is essential for diagnosing the etiology of the disorder. In the absence of clinical orientation, a nasofibroscopy is mandatory and digestive endoscopy debatable. SPECIALIZED EXAMINATIONS: The first-line supplementary examination is a videoradiography. It consists in the patient swallowing a liquid or solid barium sulfate bolus. This detects any anatomical or functional abnormalities. It is the examination of choice for the diagnosis of inhalation and its mechanism. Videoendoscopy is complementary to videoradiography. It can be conducted in first intention in patients who cannot be transported to the radiology unit. It provides precise information on glottal closing and pharyngeal contraction. IMPACT ON MANAGEMENT: In a restricted number of patients, the precise knowledge of the mechanism of dysphagia can help to orientate specific treatment. In others, such examinations will orient re-education, postural adaptation and the modification of food texture. In many patients, precise diagnosis of the mechanism at the origin of dysphagia has no impact on the management of dysphagia.

[Deglutition disorders in the elderly. Management]. / Les troubles de la déglutition du sujet âgé. Prise en charge.

GENERAL PRINCIPLES: The management of dysphagia requires multi-disciplinary interventions, implying various procedures, the choice of which depends on the results of the global prior assessment of the patient. General measures for oral hygiene, dental care and the organization of conditions in which meals are taken are essential, particularly for dependent patients. A change in food texture or in viscosity of liquids is a strategy commonly used. However, such changes must depend on objective bases and not unnecessarily penalize patients or expose them to further risks of complications. COMPENSATION AND RE-EDUCATION TECHNIQUES: Various strategies can help to counteract deficient deglutition mechanisms. Among these, adopting a particular position while swallowing is helpful in many dysphagic patients, but may be limited by severe cervical stiffness. The swallow reflex can be enhanced by sensorial stimulation techniques, although they are only effective short-term. Execution of voluntary maneuvers improves efficacy and safety when swallowing, but learning these maneuvers can be difficult or even impossible, even when accepted by the patients and compliance is inconsistent. Re-education techniques are intended to lastingly improve swallowing, but it is difficult to obtain the active participation of many elderly patients. Furthermore, these commonly used techniques lack seriousness and require validation. MISCELLANEOUS PROCEDURES: The efficacy of pharmacological intervention is not clear, other than in certain particular etiological contexts and, as with procedures enhancing the stimulating properties of food and liquids, will obviously be developed in the future. Surgery, or related techniques, provides help in certain specific conditions, notably when an anatomical disorder is responsible for the disorder. Gastrostomy is still controversial, not only with regard to its optimal practical use and its capacity to decrease respiratory infection risks and improve nutritional prognosis, but also with regard to its impact on patients' survival and quality of life.

[Highly elevated alphafetoprotein and hepatic cirrhosis. It is not always hepatocarcinoma]. / Alpha-foetoprotéine très élevée et cirrhose hépatique. Ce n'est pas toujours un hépatocarcinome.

BACKGROUND: Alphafetoprotein assay contributes considerably to the diagnosis of hepatocarcinoma in patients with hepatic cirrhosis. We report the case of a cirrhotic patient whose elevated alphafetoprotein level was not associated with liver disease. CASE REPORT: Alphafetoprotein level was followed in a 64-year-old man with hepatic cirrhosis. A rise from 415 to 7690 ng/ml between June and November 1997 led to the discovery of adenocarcinoma of the cardia with liver metastasis. This extrahepatic adenocarcinoma was probably the cause of inappropriate secretion of alphafetoprotein. DISCUSSION: Primary liver tumors are obviously not the only source of elevated alphafetoprotein levels. High levels can also be observed in certain, notably digestive tract and embryonary, cancers. Gastric hepatoid adenocarcinoma is a recently described histological entity first described in 1970. Typically, there is an inappropriate secretion of alphafetoprotein due to a secondary liver tumor.

A prospective and comparative study between stapled hemorrhoidopexy and hemorrhoidal artery ligation with mucopexy.

AIM: The aim of this study was to compare the efficacy between stapled hemorrhoidopexy (Longo technique) and transanal hemorrhoidal artery ligation with mucopexy (THDm) in the treatment of hemorrhoidal disease. PATIENTS AND METHODS: From June 2009 to January 2011, 81 patients having grade II or III hemorrhoidal disease underwent prospective evaluation followed by surgery at two centers (27 Longo and 54 THDm). Symptoms (bleeding, tenesmus, prolapse, fecal incontinence, pain) and the satisfaction score were compared on the first post-operative day and at 1, 6, 12, and 24 months thereafter. The follow-up was 24 months. RESULTS: There was no difference in mean length of stay. One complication (recto-vaginal fistula) was observed after Longo. The prolapse score was significantly lower after THDm than after Longo on the first post-operative day (P < 0.0015). Bleeding score after THDm was significantly lower on the first post-operative day (P = 0.04), but higher thereafter (P = 0.03 and P = 0.04). Tenesmus score after THDm was significantly lower for the first three months (P < 0.06 and 0.001). On the first post-operative day and at one month, the visual analog pain score was significantly lower after THDm than that after Longo (P < 0.0003 et P < 0.01). On the first post-operative day and at one month, the satisfaction score was higher after THDm than after Longo (P < 0.001). CONCLUSION: THDm was safe and effective. Short-term outcomes after THDm were better than after Longo but long-term results seemed to be similar.

Olmesartan-associated enteropathy: results of a national survey.

BACKGROUND: Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan. AIM: To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans. METHODS: French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included. RESULTS: Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration). CONCLUSIONS: Olmesartan causes a severe and immune-mediated enteropathy, with or without villous atrophy. Enteropathy associated with other sartans seems to be very rare.

Clinical trial: Radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients.

BACKGROUND: Radiofrequency (RF) energy delivery is an endoscopic procedure developed for the treatment of gastro-oesophageal reflux disease. AIM: To compare RF and a proton pump inhibitor strategy (PPI) in PPI-dependent patients by carrying out a prospective, randomized trial. METHODS: Patients with PPI-dependent typical reflux symptoms were randomly allocated to either RF or PPI regimen alone. The primary endpoint, evaluated at 6-month, was defined as the possibility for the patient to stop or to decrease PPI use to <50% of the effective dose required at baseline. RESULTS: In the RF group, 18/20 patients stopped (n = 3) or decreased (n = 15) PPI use as compared to eight of 16 in the PPI group (P = 0.01). None of the control patients could stop PPI. Health-related quality of life scores were not different between groups. No significant change in oesophageal acid exposure (OAE) was noted between baseline and 6-months after RF. No severe complication was reported. CONCLUSIONS: Radiofrequency energy delivery is a safe and effective therapeutic option, allowing reduction in or discontinuation of PPI therapy in patients with PPI-dependent symptoms, without loss of quality of life. However, in a majority of patients, PPI therapy cannot be completely stopped. The efficacy of RF does not seem to be related to a decrease in OAE.

Function of upper esophageal sphincter during swallowing: the grabbing effect.

This study investigated deglutitive axial force developed within the pharynx, upper esophageal sphincter (UES), and cervical esophagus. Position and deglutitive excursion of the UES were determined using combined manometry and videofluoroscopy in eight healthy volunteers. Deglutitive clearing force was quantified with a force transducer to which nylon balls of 6- or 8-mm diameter were tethered and positioned within the oropharynx, hypopharynx, UES, and cervical esophagus. Axial force recordings were synchronized with videofluoroscopic imaging. Clearing force was dependent on both sphere diameter (P < 0.05) and location, with greater force exhibited in the hypopharynx and UES compared with the oropharynx and esophagus (P < 0.05). Within the UES, the onset of traction force coincided with passage of the pharyngeal clearing wave but persisted well beyond this. On videofluoroscopy, the persistent force was associated with the aboral motion of the ball caught within the UES. Force abated with gradual slippage of the UES around the ball. The force attributable to the combination of UES contraction and laryngeal descent was named the grabbing effect. The grabbing effect functions to transfer luminal contents distal to the laryngeal inlet at the end of the pharyngeal swallow, presumably acting to prevent regurgitation and/or aspiration of swallowed material.

Deglutitive tongue force modulation by volition, volume, and viscosity in humans.

BACKGROUND/AIMS: Deglutitive tongue biomechanics are complex, involving bolus containment, loading, and propulsion. This study aimed to quantify the modulation of deglutitive pulsive and clearing tongue forces in varied swallowing conditions. METHODS: Oropharyngeal pressure and force were recorded using sensing bulbs and strain-gauge manometry in 8 volunteers during swallows of varied volume and viscosity. Volitional modulation was explored with forceful and attenuated swallows. RESULTS: Temporal analysis confirmed that bulb recordings corresponded to tongue pulsive force, and the strain-gauge recordings measured tongue clearing pressure. Volition was the most potent modifier of both tongue pulsive force and clearing pressure with values showing a fourfold increase from attenuated to forceful swallows. Bolus viscosity also induced an increase of tongue pulsive force and clearing pressure by the oral tongue. Volitional control as well as adaptation to viscosity was greatest on the anterior and middle part of the oral tongue. There was no force adaptation with increased bolus volume. CONCLUSIONS: Tongue pulsive force and clearing pressure during swallow showed substantial modulation for bolus viscosity that can be reproduced by volitional control. The anterior two thirds of the tongue showed both greater forces and greater modulation than did the tongue base.