Rome IV. Gallbladder and Sphincter of Oddi Disorders.

The concept that motor disorders of the gallbladder, cystic duct and sphincter of Oddi can cause painful syndromes is attractive and popular, at least in the USA. However, the results of commonly performed ablative treatments (cholecystectomy and sphincterotomy) are not uniformly good. The predictive value of tests that are often used to diagnose dysfunction (dynamic gallbladder scintigraphy and sphincter manometry) is controversial. Evaluation and management of these patients is made difficult by the fluctuating symptoms and the placebo effect of invasive interventions. A recent stringent study has shown that sphincterotomy is no better than sham treatment in patients with post-cholecystectomy pain and little or no objective abnormalities on investigation, so that the old concept of sphincter of Oddi dysfunction (SOD) type III is discarded. ERCP approaches are no longer appropriate in that context. There is a pressing need for similar prospective studies to provide better guidance for clinicians dealing with these patients. We need to clarify the indications for cholecystectomy in patients with Functional Gallbladder Disorder (FGBD) and the relevance of sphincter dysfunction in patients with some evidence for biliary obstruction (previously SOD type II, now called "Functional Biliary Sphincter Disorder - FBSD") and with idiopathic acute recurrent pancreatitis.

Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs: A Comparison With Adolescent and Young Adults.

AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data.

Somatic tinnitus prevalence and treatment with tinnitus retraining therapy.

OBJECTIVES: Somatic tinnitus originates from increased activity of the dorsal cochlear nucleus, a cross-point between the somatic and auditory systems. Its activity can be modified by auditory stimulation or somatic system manipulation. Thus, sound enrichment and white noise stimulation might decrease tinnitus and associated somatic symptoms. The present uncontrolled study sought to determine somatic tinnitus prevalence among tinnitus sufferers, and to investigate whether sound therapy with counselling (tinnitus retraining therapy; TRT) may decrease tinnitus-associated somatic symptoms. METHODS: To determine somatic tinnitus prevalence, 70 patients following the TRT protocol completed the Jastreboff Structured Interview (JSI) with additional questions regarding the presence and type of somatic symptoms. Among 21 somatic tinnitus patients, we further investigated the effects of TRT on tinnitus-associated facial dysesthesia. Before and after three months of TRT, tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI), and facial dysesthesia was assessed with an extended JSI-based questionnaire. RESULTS: Among the evaluated tinnitus patients, 56% presented somatic tinnitus-including 51% with facial dysesthesia, 36% who could modulate tinnitus by head and neck movements, and 13% with both conditions. Self-evaluation indicated that TRT significantly improved tinnitus and facial dysesthesia in 76% of patients. Three months of TRT led to a 50% decrease in mean THI and JSI scores regarding facial dysesthesia. CONCLUSIONS: Somatic tinnitus is a frequent and underestimated condition. We suggest an extension of the JSI, including specific questions regarding somatic tinnitus. TRT significantly improved tinnitus and accompanying facial dysesthesia, and could be a useful somatic tinnitus treatment.

[Somatic tinnitus (review). A consequence of plasticity and bimodal integration in the dorsal cochlear nucleus]. / Les somatoacouphènes (revue) : une conséquence de la plasticité et de l'int gration bimodale dans le noyau cochléaire dorsal.

Somatic tinnitus is a peculiar tinnitus type that can be defined as a tinnitus that can be modulated in intensity and/or pitch by manipulating some regions of the head and neck but also as tinnitus associated with facial pain or dysesthesis in the same area. Those areas are innervated by the trigeminal nerve and the cervical plexus. This can be explained by functional connections between the trigeminal system and the auditory brainstem and mid-brain. A literature overview shows how different messages coming from the head and neck are able to modulate the hearing information. Tinnitus is generated by an increase of the spontaneous discharges of the dorsal cochlear nucleus neurons, tonotopic reorganisation and an increase of the neural synchronism in the auditory cortex. Trigeminal stimulations have an influence on the activity of the dorsal cochlear nucleus especially in case of an associated hearing loss.

Gadolinium as an alternative contrast agent for therapeutic ERCP in the iodine-allergic patient.

Performance of endoscopic retrograde cholangiopancreatography (ERCP) requires an intraductal contrast agent. The contrast of choice is an iodine-based agent. The alternatives in patients with a severe allergy to iodinated contrast are limited. We undertook a retrospective review of the success and safety of gadolinium as an alternative radiocontrast agent in patients with allergy to iodine-based contrast in a series of five patients in a tertiary care pancreaticobiliary referral center. The five patients underwent a total of six ERCP procedures using a gadolinium chelate as the radiocontrast agent. ERCP was technically successful in all cases, including pancreatic endotherapy. There were no contrast-related adverse reactions. Gadolinium is concluded to be a reasonable alternative to iodine-based ERCP contrast in selected patients. It provides inferior image quality compared to standard iodine-based contrast but was not technically limiting in our small experience.

The revised Atlanta criteria more accurately reflect severity of post-ERCP pancreatitis compared to the consensus criteria.

Background and objective: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most prevalent complication after ERCP with an incidence of 3.5%. PEP severity is classified according to either the consensus criteria or the revised Atlanta criteria. In this international cohort study we investigated which classification is the strongest predictor of PEP-related mortality. Methods: We reviewed 13,384 consecutive ERCPs performed between 2012 and 2017 in eight hospitals. We gathered data on all pancreatitis-related adverse events and compared the predictive capabilities of both classifications. Furthermore, we investigated the correlation between the two classifications and identified reasons underlying length of stay. Results: The total sample consisted of 387 patients. The revised Atlanta criteria have a higher sensitivity (100 vs. 55%), specificity (98 vs. 72%) and positive predictive value (58 vs. 5%). There is a significant difference (p < 0.001) between the two classifications. In 124 patients (32%), the length of stay was influenced by concomitant diseases. Conclusion: The revised Atlanta classification is superior in predicting mortality and better reflects PEP severity. This has important implications for researchers, clinicians and patients. For the diagnosis of PEP pancreatitis, the consensus criteria remain the golden standard. However, the revised Atlanta criteria are preferable for defining PEP severity.

Small prophylactic pancreatic duct stents: an assessment of spontaneous passage and stent-induced ductal abnormalities.

BACKGROUND AND STUDY AIMS: Placing small stents in the pancreatic duct at endoscopic retrograde cholangiopancreatography reduces the risk of pancreatitis. However, this practice means that a second procedure might be required to remove the stent, and stents can also damage the duct. The aims of this study were to determine the frequency of spontaneous dislodgment and to assess the incidence of stent-induced ductal irregularities. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive patients seen over a 3-year period (2001 - 2004) who had undergone placement of a 3-Fr pancreatic duct stent and in whom the fate of the stent had been documented. Radiographs were reviewed to determine stent passage at 30 days. If applicable, follow-up pancreatograms were reviewed to assess for stent-induced ductal abnormalities. Statistical analysis was performed using chi-squared and Fisher's exact tests for proportions, and 95 % binomial confidence intervals (CI) were calculated. RESULTS: Records for 125 consecutive patients who had had 3-Fr pancreatic stents placed were reviewed. The stents had passed spontaneously within 30 days in 110/125 patients (88 %). In the remaining 15 patients (12 %, 95 % CI 6.9 % - 19 %), the stents were still present on follow-up radiographs after a median time of 36 days, (range 31 - 116 days). Stent length, pancreatic sphincterotomy, and pancreas divisum had no effect on the likelihood of spontaneous passage. No stent-induced ductal irregularities were observed. CONCLUSIONS: Nearly 90 % of prophylactic 3-Fr pancreatic duct stents pass spontaneously within 30 days, and these stents were not observed to induce changes in the pancreatic duct.

Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia.

BACKGROUND AND STUDY AIMS: The most permanent method of treating achalasia is a surgical myotomy. Because of the requirement for a mucosal incision and the risk of perforation, this procedure has not generally been approached endoscopically. We hypothesized that we could perform a safe and robust myotomy by working in the submucosal space, accessed from the esophageal lumen. MATERIALS AND METHODS: Four pigs were used for this experiment. Baseline lower esophageal sphincter (LES) pressures were recorded and the pigs underwent upper endoscopy using a standard endoscope. A submucosal saline lift was created approximately 5 cm above the LES and a small nick was made in the mucosa in order to facilitate the introduction of a dilating balloon. After dilation, the scope was introduced over the balloon into the submucosal space and advanced toward the now visible fibers of the LES. The circular layer of muscle was then cleanly incised using an electrocautery knife in a distal-to-proximal fashion, without complications. The scope was then withdrawn back into the lumen and the mucosal defect was closed with endoscopically applied clips. The entire procedure took less than 15 minutes. Manometry was repeated on day 5 after the procedure and the animals were euthanized on day 7. RESULTS: LES pressures fell significantly from an average of 16.4 mm Hg to an average of 6.7 mm Hg after the myotomy. The necropsy examinations revealed no evidence of mediastinitis or peritonitis. CONCLUSIONS: Endoscopic submucosal esophageal myotomy is feasible, safe, and effective in the short term. It has the potential for being useful in patients with achalasia. The submucosal space is a novel and potentially important field of operation for endoscopic procedures.

Peroral transgastric endoscopic primary repair of a ventral hernia in a porcine model.

BACKGROUND AND STUDY AIMS: Multiple studies have demonstrated the feasibility of peroral transgastric endoscopic procedures in animal models. The aim of the study was to evaluate the feasibility of a peroral transgastric endoscopic approach to repair abdominal wall hernias. PATIENTS AND METHODS: We performed acute experiments under general anesthesia with endotracheal intubation using 50-kg pigs. Following peroral intubation an incision of the gastric wall was made and the endoscope was advanced into the peritoneal cavity. An internal anterior abdominal wall incision was performed with a needle knife to create an animal model of a ventral hernia. After hernia creation an endoscopic suturing device was used for primary repair of the hernia. After completion of the hernia repair the endoscope was withdrawn into the stomach and the gastric wall incision was closed with endoscopic clips. Then the animals were killed for necropsy. RESULTS: Two acute experiments were performed. Incision of the gastric wall was easily achieved with a needle knife and a pull-type sphincterotome. A large (3 x 2 cm) defect of the abdominal wall (ventral hernia model) was closed with five or six sutures using the endoscopic suturing device. Postmortem examination revealed complete closure of the hernia without any complications. CONCLUSIONS: Transgastric endoscopic primary repair of ventral hernias in a porcine model is feasible and may be technically simpler than laparoscopic surgery.

Preliminary pneumoperitoneum facilitates transgastric access into the peritoneal cavity for natural orifice transluminal endoscopic surgery: a pilot study in a live porcine model.

BACKGROUND AND STUDY AIMS: Safe entrance into the peritoneal cavity through the gastric wall is paramount for the successful clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim of the study was to develop alternative safe transgastric access to the peritoneal cavity. PATIENTS AND METHODS: We performed 11 survival experiments on 50-kg pigs. In sterile conditions, the abdominal wall was punctured with a Veress needle. The peritoneal cavity was insufflated with 2 L carbon dioxide (CO (2)). A sterile endoscope was introduced into the stomach through a sterile overtube; the gastric wall was punctured with a needle-knife; after balloon dilation of the puncture site, the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with biopsies from abdominal wall, liver and omentum, was performed. The endoscope was withdrawn into the stomach. The animals were kept alive for 2 weeks and repeat endoscopy was followed by necropsy. RESULTS: The pneumoperitoneum, easily created with the Veress needle, lifted the abdominal wall and made a CO (2)-filled space between the stomach and adjacent organs, facilitating gastric wall puncture and advancement of the endoscope into the peritoneal cavity. There were no hemodynamic changes or immediate or delayed complications related to pneumoperitoneum, transgastric access, or intraperitoneal manipulations. Follow-up endoscopy and necropsy revealed no problems or complications inside the stomach or peritoneal cavity. CONCLUSIONS: Creation of a preliminary pneumoperitoneum with a Veress needle facilitates gastric wall puncture and entrance into the peritoneal cavity without injury to adjacent organs, and can improve the safety of NOTES.

A new stapler-based full-thickness transgastric access closure: results from an animal pilot trial.

BACKGROUND AND STUDY AIMS: Reliable closure of the transluminal incision is the crucial step for natural orifice transluminal endoscopic surgery (NOTES) procedures. The aim of this study was to evaluate the feasibility and effectiveness of transgastric access closure with a flexible stapling device in a porcine survival model. PATIENTS AND METHODS: We carried out four experiments (two sterile and two nonsterile) on 50 kg pigs. The endoscope was passed through a gastrotomy made with a needle knife and an 18-mm controlled radial expansion dilating balloon. After peritoneoscopy, a flexible linear stapling device (NOLC60, Power Medical Interventions, Langhorne, Pennsylvania, USA) was perorally advanced over a guide wire into the stomach, positioned under endoscopic guidance, and opened to include the site of gastrotomy between its two arms; four rows of staples were fired. One animal was sacrificed 24 hours after the procedure (progression of pre-existing pneumonia). The remaining animals were survived for 1 week and then underwent repeat endoscopy and postmortem examination. RESULTS: Peroral delivery and positioning of the stapling device involved some technical difficulties, mostly due to the short length (60 cm) of the stapling device. The stapler provided complete leak-resistant gastric closure in all pigs. None of the surviving animals had any clinical signs of infection. Necropsy demonstrated an intact staple line with full-thickness healing of the gastrotomy in all animals. Histologic examination confirmed healing, but also revealed intramural micro-abscesses within the gastric wall after nonsterile procedure. CONCLUSIONS: Gastrotomy closure with a perorally delivered flexible stapling device created a leak-resistant transmural line of staples followed by full-thickness healing of the gastric wall incision. Increasing the length of the instrument and adding device articulation will further facilitate its use for NOTES procedures.

Neural tissues express high levels of the cellular src gene product pp60c-src.

Chicken embryo tissues were examined for the expression of pp60c-src, the normal cellular homolog of the transforming protein of Rous sarcoma virus. Three assays, including a solid-phase radioimmunoassay, a competitive radioimmunoprecipitation assay, and an immune complex protein kinase assay, were employed. Elevated levels of pp60c-src were detected in lysates from several neural tissues, including brain, retina, and spinal ganglia. Other tissues contained 8- to 10-fold-lower levels of pp60c-src, levels comparable to those found in chicken embryo fibroblasts. Expression of pp60c-src in brain tissues was also shown to vary with the developmental stage of the embryo.

Do all patients with abnormal intraoperative cholangiogram merit endoscopic retrograde cholangiopancreatography?

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used for postoperative evaluation of an abnormal intraoperative cholangiogram (IOC). Although a normal IOC is very suggestive of a disease-free common bile duct (CBD), abnormal studies are associated with high false-positive rates. This study aimed to identify a subset of patients with abnormal IOC who would benefit from a postoperative ERCP. METHODS: This prospective study investigated 51 patients with abnormal IOC at laparoscopic cholecystectomy who underwent postoperative ERCP at two tertiary referral centers over a 3-year period. Univariate and multivariate logistic regression analyses were performed to determine predictors of CBD stones at postoperative ERCP. RESULTS: For all 51 patients, ERCP was successful. The ERCP showed CBD stones in 33 cases (64.7%), and normal results in 18 cases (35.2%). On univariate analysis, abnormal liver function tests (p < 0.0001) as well as IOC findings of a large CBD stone (p = 0.03), multiple stones (p = 0.01), and a dilated CBD (p = 0.07) predicted the presence of retained stones at postoperative ERCP. However, on multivariable analysis, only abnormal liver function tests correlated with the presence of CBD stones (p < 0.0001). CONCLUSIONS: One-third of patients with an abnormal IOC have a normal postoperative ERCP. Elevated liver function tests can help to identify patients who merit further evaluation by ERCP. The use of less invasive methods such as endoscopic ultrasound or magnetic resonance cholangiopancreatography should be considered for patients with normal liver function tests to minimize unnecessary ERCPs.

Transgastric endoscopic splenectomy: is it possible?

BACKGROUND: We have previously reported the feasibility of diagnostic and therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal ligation by an oral transgastric approach. We present results of per-oral transgastric splenectomy in a porcine model. The goal of this study was to determine the technical feasibility of per-oral transgastric splenectomy using a flexible endoscope. METHODS: We performed acute experiments on 50-kg pigs. All animals were fed liquids for 3 days prior to procedure. The procedures were performed under general anesthesia with endotracheal intubation. The flexible endoscope was passed per orally into the stomach and puncture of the gastric wall was performed with a needle knife. The puncture was extended to create a 1.5-cm incision using a pull-type sphincterotome, and a double-channel endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated with air through the endoscope. The spleen was visualized. The splenic vessels were ligated with endoscopic loops and clips, and then mesentery was dissected using electrocautery. RESULTS: Endoscopic splenectomy was performed on six pigs. There were no complications during gastric incision and entrance into the peritoneal cavity. Visualization of the spleen and other intraperitoneal organs was very good. Ligation of the splenic vessels and mobilization of the spleen were achieved using commercially available devices and endoscopic accessories. CONCLUSIONS: Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned.

Widespread endoscopic mucosal resection of the esophagus with strategies for stricture prevention: a preclinical study.

BACKGROUND AND STUDY AIMS: Circumferential endoscopic mucosal resection of the esophagus is complicated by stricture formation. Prophylactic measures for avoiding such strictures have not been well studied. The aim of this preclinical study was to assess strategies for prevention of esophageal strictures in a porcine model following widespread endoscopic mucosal resection (EMR). METHODS: A total of 18 60-kg pigs were included in the study. The roles of strip width (group 1), prophylactic steroids (group 2), and prophylactic stents (group 3) in the prevention of post-mucosectomy strictures were studied. Six animals were included in each group. Esophageal mucosal resection was achieved using a novel widespread EMR technique previously described by our group. Animals in group 1 underwent partial (50% circumference) mucosal resection without prophylactic measures, while animals in the other two groups underwent circumferential mucosal resection. Animals in group 2 received 80 mg of triamcinolone injected directly into the exposed submucosal tissue (20 mg injection in four quadrants). Animals in group 3 received esophageal metal stents coated with small-intestine submucosa (SIS) that were deployed immediately post-resection. Animals were kept alive for 1 month. RESULTS: Partial and circumferential widespread EMRs were achieved in all animals. There were no procedural complications. Repeat endoscopy at 1 month showed no strictures in group 1. Only four animals were studied in group 2, owing to the high complication rate (periesophageal abscess in all animals) with one early death. Three of the surviving animals developed mild to tight strictures. In group 3, all animals developed tight strictures; however, there was early stent migration in four animals and premature stent removal in two animals because of persistent vomiting. CONCLUSIONS: Partial widespread EMR of the esophagus heals without stricture formation and does not require prophylactic intervention. The use of deep mural steroid injection following a circumferential resection does not appear to prevent strictures and may result in serious adverse events. Short-term use of esophageal stents is inadequate for stricture prevention. However, better results may be anticipated with longer term (at least 6 weeks) stent use.

Characterization of a SNF1 homologue from the phytopathogenic fungus Sclerotinia sclerotiorum.

In yeast, the SNF1 gene product is essential for the release of catabolic repression. We report the isolation and characterization of an SNF1 homologue from the necrotrophic pathogen Sclerotinia sclerotiorum. Ss snf1 encodes a 765-amino-acid protein in which the catalytic domain has an overall identity with the yeast proteins varying from 55 to 76% while the C-terminal half of Ss SNF1 has a weak homology of about 20% with the yeast sequences. Reverse transcription-polymerase chain reaction showed that its transcripts were weakly and constitutively expressed in planta and in vitro regardless of the nature of the carbon sources and of the presence or absence of glucose. Expression of Ss snf1 in yeast cells allowed the snf1 mutant cells to utilize sucrose, raffinose or glycerol for growth while expression of the Ss snf1 catalytic domain did not restore growth on raffinose or glycerol. Ss SNF1 is structurally homologous to Snf1p, suggesting that the interactions between the kinase and the accessory subunits to activate the enzymatic complex are conserved in fungi.

The affective experience of residency training in community psychiatry.

The community setting arouses disturbing feelings (of anxiety, loneliness, anger, and disappointment) within the resident in a manner that is both unique and potentially constructive for his development as a clinician. The examination of these feelings in the supervisory setting and through peer supervision is crucial to the success of the resident's work in the community.

Assessing the acute inpatient psychiatric needs of the state hospital patient.

Regulators have a major opportunity to enhance the community care of former state hospital patients through their power to authorize additional general hospital psychiatric beds. The authors propose a series of clinical criteria for such regulators based on a review of state hospital admissions. These include provisions for patients who have chronic illness with repeated hospitalizations, who are involuntarily admitted, who have alcoholism, and who are impoverished. Further implications for general hospital units include specific changes in their treatment strategy, their links to facilities for ambulatory patients, and their provisions for staff education and support.

Dissimilar dosing with high-potency and low-potency neuroleptics.

The authors studied high-potency versus low-potency neuroleptic dosing practices for 110 Boston-area psychiatric inpatients and compared the findings with the dosing practices reported in surveys of nearly 16,000 Veterans Administration patients. Mean chlorpromazine equivalent doses for the most common agents correlated strongly in both samples. Although frequencies of lower doses of both types of agents were similar, doses of potent drugs above the daily equivalent of 1 g of chlorpromazine accounted for more than 40% of prescriptions. The mean chlorpromazine-equivalent dose of popular potent agents (haloperidol or fluphenazine) was 3.54 times as high as that of popular low-potency agents (chlorpromazine or thioridazine). Potent agents are commonly used in mania and schizophrenia, often in relatively high doses, which may carry an excess of risk over unproven added benefit.

Predictors of community tenure of discharged state hospital patients.

Community treatment of formerly hospitalized patients is in need of evaluation. The authors evaluated an aftercare program by examining its effect on the amount of time spent in the community by patients discharged from a state mental hospital. They assessed the impact of specific intervention in the areas of housing, employment, finances, psychiatric treatment, medication, and leisure. They conclude that assistance during the transition from the hospital to the community prolonged community tenure, that intervention in the areas of housing, finances, and medication was especially important, and that treatment in the community increased the amount of time spent in the community during the first 6 months after discharge.