Clinical utility of cricopharyngeal distensibility measurements during endoscopic myotomy for Zenker's diverticulum.

BACKGROUND AND AIMS: Flexible endoscopic cricopharyngeal myotomy (FECM) allows minimally invasive treatment of patients with Zenker's diverticulum (ZD); however, retreatment rates are substantial. We hypothesized that the functional lumen imaging probe (FLIP) may provide insight into ZD pathophysiology and serve as an intraprocedural guide to adequacy of myotomy. METHODS: We prospectively evaluated 11 ZD patients undergoing FECM and compared the baseline cricopharyngeal (CP) distensibility with 16 control subjects. Intraprocedural CP distensibility was measured immediately pre- and postmyotomy. The CP distensibility index (CP-DI) was defined as a ratio of the narrowest cross-sectional area (nCSA) and the corresponding intrabag pressure at 40 mL distension. Same-procedure myotomy extension was undertaken in a subgroup if threshold distensibility changes were not met. RESULTS: ZD patients had reduced baseline nCSA and CP-DI compared with control subjects, (169.6 vs 227.5 mm2 [P < .001] and 3.8 vs 7.6 mm2/mm Hg [P < .001], respectively). After CP myotomy, both nCSA and CP-DI increased significantly by an average of 74.2 mm2 (95% confidence interval [CI], 35.1-113.3; P = .002) and 2.2 mm2/mm Hg (95% CI, .6-3.8; P = .01), respectively. In the subgroup with no significant change in CP distensibility after initial myotomy (n = 6), myotomy extension resulted in significant increases in both mean nCSA and CP-DI of 66.6 mm2 (95% CI, 16.4-116.8; P = .03) and 1.9 mm2/mm Hg (95% CI, .4-3.3; P = .015), respectively. There were no adverse events. CONCLUSIONS: CP distensibility is reduced in ZD patients and is partially reversible by FECM. An intraprocedural FLIP CP distensibility measurement is safe and sensitive in detecting myotomy-induced changes. These findings support using FLIP to optimize FECM outcome. Further studies are required to derive precise metrics predictive of clinical response.

Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study.

BACKGROUND AND AIMS: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.

Long-term trends in helminth infections of wood mice (Apodemus sylvaticus) from the vicinity of Malham Tarn in North Yorkshire, England.

Helminth infections in wood mice (n = 483), trapped over a period of 26 years in the woods surrounding Malham Tarn in North Yorkshire, were analysed. Although 10 species of helminths were identified, the overall mean species richness was 1.01 species/mouse indicating that the helminth community was relatively depauperate in this wood mouse population. The dominant species was Heligmosomoides polygyrus, the prevalence (64.6%) and abundance (10.4 worms/mouse) of which declined significantly over the study period. Because of the dominance of this species, analyses of higher taxa (combined helminths and combined nematodes) also revealed significantly declining values for prevalence, although not abundance. Helminth species richness (HSR) and Brillouin's index of diversity (BID) did not show covariance with year, neither did those remaining species whose overall prevalence exceeded 5% (Syphacia stroma, Aonchotheca murissylvatici and Plagiorchis muris). Significant age effects were detected for the prevalence and abundance of all higher taxa, H. polygyrus and P. muris, and for HSR and BID, reflecting the accumulation of helminths with increasing host age. Only two cases of sex bias were found; male bias in abundance of P. muris and combined Digenea. We discuss the significance of these results and hypothesize about the underlying causes.

Elimination of Taenia solium Transmission in Northern Peru.

BACKGROUND: Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS: We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS: Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS: We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).

The interobserver agreement of optical features used to differentiate benign from neoplastic biliary lesions assessed at balloon-assisted cholangioscopy.

BACKGROUND AND AIM: Balloon-assisted cholangioscopy allows mucosal assessment of the biliary tree with pediatric endoscopes. No validated optical criteria exist to differentiate benign from neoplastic biliary lesions. We aimed to identify, validate, and revalidate optical features differentiating benign from neoplastic biliary lesions. Furthermore, we aimed to determine whether cholangioscopic appearance allows endoscopists to accurately differentiate benign from neoplastic biliary lesions. METHODS: Baseline: from 44 de-identified balloon-assisted cholangioscopy videos, a blinded investigator analyzed potential optical features distinguishing benign from neoplastic biliary lesions. VALIDATION: during the initial "teaching phase," 20 endoscopists viewed video clips of 11 optical features identified in the baseline study. At the subsequent "test phase," 20 further video clips were assessed by the endoscopists blinded to clinical details and questionnaires completed for the presence or absence of optical features, favored diagnosis and diagnostic confidence. Revalidation: The six identified optical features from the validation study with at least moderate agreement were revalidated the same way 12 months later assessing 20 new lesions. RESULTS: Baseline: 11 optical features were found to differentiate benign from neoplastic biliary lesions. Validation and revalidation: six optical features demonstrated at least moderate interobserver agreement (irregular margin, dark mucosa, adherent mucous, papillary projections, tubular, or branched/disorganized surface structures). Endoscopists correctly diagnosed lesions as benign in 89% and neoplastic in 83%. When highly confident, endoscopists correctly diagnosed 96% of benign and 87% neoplastic lesions. CONCLUSIONS: Six features were validated and revalidated to differentiate benign from neoplastic biliary lesions. When highly confident with a diagnosis, endoscopists usually differentiate benign from neoplastic biliary lesions.

Intense Focus of Alveolar Echinococcosis, South Kyrgyzstan.

Human alveolar echinococcosis (AE) is a highly pathogenic zoonotic parasitic disease caused by Echinococcus multilocularis. An ultrasound study in southern Kyrgyzstan during 2012 revealed a prevalence of 4.2% probable or confirmed AE and an additional 2.2% possible AE, representing an emerging situation. The risk for probable or confirmed AE was significantly higher in dog owners.

Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. METHODS: Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI] <150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. RESULTS: CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. CONCLUSIONS: In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Role of balloon-assisted cholangioscopy in a multiethnic cohort to assess complex biliary disease (with videos).

BACKGROUND: Cholangioscopy is used to diagnose and treat various biliary lesions. Balloon-assisted cholangioscopy (BAC) has mostly been reported in Asian patients with large bile ducts. OBJECTIVE: To assess the feasibility and accuracy of performing BAC in complex biliary diseases in Australian patients. DESIGN: Prospective observational study. SETTING: A single Australian tertiary referral hospital. PATIENTS: Fifty-nine consecutive patients (55 non-Asian ethnicity). INTERVENTIONS: BAC using ultrathin endoscopes. MAIN OUTCOME MEASUREMENTS: Procedural success rates, diagnostic accuracy, and adverse event rates. RESULTS: Fifty-nine patients underwent 76 BAC procedures for indeterminate biliary lesions, ampullary adenomas, and difficult stone disease. The technical success rate was 93%. The median bile duct diameter was 7 mm (range, 2-20). Of 34 indeterminate biliary strictures, 22 appeared benign and 12 malignant on BAC appearance alone. All benign-appearing strictures were confirmed benign, whereas 9 of 12 malignant-appearing strictures were confirmed malignant by biopsy sampling or follow-up (sensitivity 100% [95% CI, 66%-100%], specificity 88% [95% CI, 69%-97%], positive predictive value 75% [95% CI, 42%-93%], negative predictive value 100% [95% CI, 82%-100%]). BAC appearance correctly diagnosed indeterminate masses as benign (4/4) or malignant (3/3). Eight patients were assessed for bile duct extension of ampullary adenomas and 5 of 6 had biliary stones cleared directly or with holmium laser lithotripsy. Adequate histopathologic specimens were obtained from 31 of 39 (79%) attempted biopsy specimens. The adverse event rate was 8%. LIMITATIONS: A single-center, single endoscopist experience. CONCLUSIONS: In a largely non-Asian cohort with smaller bile ducts, BAC can be performed with high success and acceptable adverse event rates. BAC is particularly useful in differentiating benign from malignant indeterminate biliary lesions.

A random forest approach for predicting the presence of Echinococcus multilocularis intermediate host Ochotona spp. presence in relation to landscape characteristics in western China.

Understanding distribution patterns of hosts implicated in the transmission of zoonotic disease remains a key goal of parasitology. Here, random forests are employed to model spatial patterns of the presence of the plateau pika (Ochotona spp.) small mammal intermediate host for the parasitic tapeworm Echinococcus multilocularis which is responsible for a significant burden of human zoonoses in western China. Landsat ETM+ satellite imagery and digital elevation model data were utilized to generate quantified measures of environmental characteristics across a study area in Sichuan Province, China. Land cover maps were generated identifying the distribution of specific land cover types, with landscape metrics employed to describe the spatial organisation of land cover patches. Random forests were used to model spatial patterns of Ochotona spp. presence, enabling the relative importance of the environmental characteristics in relation to Ochotona spp. presence to be ranked. An index of habitat aggregation was identified as the most important variable in influencing Ochotona spp. presence, with area of degraded grassland the most important land cover class variable. 71% of the variance in Ochotona spp. presence was explained, with a 90.98% accuracy rate as determined by 'out-of-bag' error assessment. Identification of the environmental characteristics influencing Ochotona spp. presence enables us to better understand distribution patterns of hosts implicated in the transmission of Em. The predictive mapping of this Em host enables the identification of human populations at increased risk of infection, enabling preventative strategies to be adopted.

Dog ownership, dog behaviour and transmission of Echinococcus spp. in the Alay Valley, southern Kyrgyzstan.

Echinococcosis is a re-emerging zoonotic disease in Kyrgyzstan, and the incidence of human infection has increased substantially since the collapse of the Soviet Union in 1991. Domestic dogs are hosts of Echinococcus spp. and play an important role in the transmission of these parasites. The demography, ecology and behaviour of dogs are therefore relevant in studying Echinococcus spp. transmission. Dog demographics, roles of dogs, dog movements and faecal environmental contamination were assessed in four rural communities in the Alay Valley, southern Kyrgyzstan. Arecoline purge data revealed for the first time that E. granulosus, E. canadensis and E. multilocularis were present in domestic dogs in the Alay Valley. Surveys revealed that many households had dogs and that dogs played various roles in the communities, as pets, guard dogs or sheep dogs. Almost all dogs were free to roam, and GPS data revealed that many moved outside their communities, thus being able to scavenge offal and consume rodents. Faecal environmental contamination was high, presenting a significant infection risk to the local communities.

Transmission ecosystems of Echinococcus multilocularis in China and Central Asia.

From continental to regional scales, the zoonosis alveolar echinococcosis (AE) (caused by Echinococcus multilocularis) forms discrete patches of endemicity within which transmission hotspots of much larger prevalence may occur. Since the late 80s, a number of hotspots have been identified in continental Asia, mostly in China, wherein the ecology of intermediate host communities has been described. This is the case in south Gansu, at the eastern border of the Tibetan plateau, in south Ningxia, in the western Tian Shan of Xinjiang, and in the Alay valley of south Kyrgyzstan. Here we present a comparative natural history and characteristics of transmission ecosystems or ecoscapes. On this basis, regional types of transmission and their ecological characteristics have been proposed in a general framework. Combining climatic, land cover and intermediate host species distribution data, we identified and mapped 4 spatially distinct types of transmission ecosystems typified by the presence of one of the following small mammal 'flagship' species: Ellobius tancrei, Ochotona curzoniae, Lasiopodomys brandtii or Eospalax fontanierii. Each transmission ecosystem had its own characteristics which can serve as a reference for further in-depth research in the transmission ecology of E. multilocularis. This approach may be used at fine spatial scales to characterize other poorly known transmission systems of the large Eurasian endemic zone, and help in consideration of surveillance systems and interventions.

Detection of human taeniases in Tibetan endemic areas, China.

Detection of taeniasis carriers of Taenia solium is essential for control of cysticercosis in humans and pigs. In the current study, we assessed the positive detection rate of a self-detection tool, stool microscopy with direct smear and coproPCR for taeniasis carriers in endemic Tibetan areas of northwest Sichuan. The self-detection tool through questioning about a history of proglottid expulsion within the previous one year showed an overall positive detection rate of more than 80% for Taenia saginata, T. solium and T. asiatica. The positive detection rate was similar for T. saginata and T. solium. In 132 taeniid tapeworm carriers, 68 (51·5%) were detected by microscopy and 92 (69·7%) were diagnosed by coproPCR. A combination of microscopy and coproPCR increased the positive detection rate to 77·3%. There remained 10 cases (7·6%) coproPCR negative but microscopy positive. Due to the high cost and complicated process, coproPCR is required for the identification of Taenia species only when necessary, though it had a significant higher positive detection rate than microscopy. Combined use of self-detection and stool microscopy are recommended in community-based mass screening for taeniases in this Tibetan area or in other situation-similar endemic regions.

Advances in diagnosis and spatial analysis of cysticercosis and taeniasis.

Human cysticercosis, caused by accidental ingestion of eggs of Taenia solium, is one of the most pathogenic helminthiases and is listed among the 17 WHO Neglected Tropical Diseases. Controlling the life-cycle of T. solium between humans and pigs is essential for eradication of cysticercosis. One difficulty for the accurate detection and identification of T. solium species is the possible co-existence of two other human Taenia tapeworms (T. saginata and T. asiatica, which do not cause cysticercosis in humans). Several key issues for taeniasis/cysticercosis (T/C) evidence-based epidemiology and control are reviewed: (1) advances in immunological and molecular tools for screening of human and animals hosts and identification of Taenia species, with a focus on real-time detection of taeniasis carriers and infected animals in field community screenings, and (2) spatial ecological approaches that have been used to detect geospatial patterns of case distributions and to monitor pig activity and behaviour. Most recent eco-epidemiological studies undertaken in Sichuan province, China, are introduced and reviewed.

Pancreatoscopy-guided laser lithotripsy to manage obstructing intraductal pancreatic calculi.

Video 1Pancreatoscopy-guided laser lithotripsy to manage obstructing intraductal pancreatic calculi.

Molecular identification of Echinococcus species from eastern and southern Qinghai, China, based on the mitochondrial cox1 gene.

The Qinghai-Tibetan Plateau (QTP, in western China), which is the largest and highest plateau on Earth, is a highly epidemic region for Echinococcus spp. We collected 70 Echinococcus samples from humans, dogs, sheep, yaks, plateau pikas, and voles in eastern and southern Qinghai and genotyped them using the mitochondrial DNA marker cytochrome oxidase subunit I gene and maximum parsimony and Bayesian reconstruction methods. Based on the 792-bp sequence matrix, we recorded 124 variable sites, of which, 115 were parsimony-informative. Thirty-four haplotypes (H1-H34) were detected, of which H1-H15, H16-H17, and H18-H34 belonged to Echinococcus shiquicus, Echinococcus multilocularis, and Echinococcus granulosus, respectively. Within 26 human isolates, three were identified as E. multilocularis and 23 were E. granulosus. We also detected a dual infection case in a dog with E. multilocularis and E. granulosus. The intraspecific haplotype (Hd ± SD) and nucleotide (Nd ± SD) diversity of E. shiquicus (0.947 ± 0.021; 0.00441 ± 0.00062) was higher than that for E. granulosus (0.896 ± 0.038; 0.00221 ± 0.00031) and E. multilocularis (0.286 ± 0.196; 0.00036 ± 0.00025). Moreover, the haplotype network of E. shiquicus showed a radial feature rather than a divergent feature in a previous study, indicating this species in the QTP has also evolved with bottleneck effects.

Role of endoscopic stenting for biliary strictures in chronic pancreatitis.

AIM: To review the published work concerning the role of biliary stenting for chronic pancreatitis-related strictures. METHODS: A case study in which multiple plastic stents are used to manage a chronic pancreatitis biliary stricture is presented, and the published work reviewed. RESULTS: There has been a gradual evolution in the endoscopic management of distal biliary strictures secondary to chronic pancreatitis. Most early series used single (usually 10 F) plastic stents for varying time periods. Long-term stricture resolution occurred in only approximately 25% of patients and stent-related complications were high if stent exchanges were not performed routinely every 3-4 months. Recent studies using multiple (≥ 3) 10 F stents placed sequentially every few months for approximately 12 months have resulted in resolution of biliary strictures in up to 90% of patients. In general, the use of both uncovered and partially covered self-expandable metal stents for biliary strictures due to chronic pancreatitis have been disappointing due to problems with epithelial hyperplasia involving the uncovered portions of the self-expandable metal stents resulting in late stent occlusion and other problems. Similarly, early published data does not at this stage support the routine use of fully covered self-expandable metal stents because of unacceptable stent-related complications. CONCLUSION: Chronic pancreatitis-related biliary strictures should be managed initially with sequentially-placed multiple 10 F plastic stents for approximately 12 months.

Differential diagnosis of Triaenophorus crassus and T. nodulosus experimental infection in Cyclops abyssorum praealpinus (Copepoda) from the Alpine Lake Grundlsee (Austria) using PCR-RFLP.

In 2005, an epidemic of the cestode Triaenophorus crassus in Arctic charr, Salvelinus umbla from Lake Grundlsee (Austria) was reported, resulting in the closure of the local fisheries. The parasite uses a copepod and a salmonid fish as intermediate hosts, and the European pike (Esox lucius) as definitive host. In Lake Grundlsee procercoids of T. crassus, T. nodulosus and Eubothrium salvelini use the copepod Cyclops abyssorum praealpinus as their first intermediate host. We report on the development of a PCR-RFLP assay for the specific differentiation between the procercoids of the three cestode species. Ban I restriction sites within a 207-bp 18S rRNA-amplified fragment yielded two and three species-specific products to unequivocally distinguish between T. crassus and T. nodulosus, respectively. The assay is sufficiently sensitive to characterise a single procercoid of both Triaenophorus species in their copepod host, enabling a direct measure of infection. This assay will be useful in monitoring the progress of the control methods currently in place.

Assessment of a 10-year dog deworming programme on the transmission of Echinococcus multilocularis in Tibetan communities in Sichuan Province, China.

Human alveolar echinococcosis (AE) is considered a neglected zoonotic disease by the World Health Organization (WHO). The causative pathogen, Echinococcus multilocularis, lives as an adult tapeworm in the intestinal tract of canines. AE was identified as an emerging public health issue in Tibetan communities of Shiqu County 20 years ago. On St. Lawrence Island, Alaska (USA), in the 1980s peri-domestic transmission of E. multilocularis was controlled by regular deworming of owned dogs over a 10-year period. In Tibetan communities, on the Tibetan Plateau, control of E. multilocularis transmission is challenging due to the continental setting, complex epidemiology, disease ecology, geography, and socio-cultural factors. However, a control programme based on deworming owned dogs using praziquental (PZQ) has been carried out since 2006. Assessment was conducted in townships where baseline data were available 10 years prior. Purging of dogs by oral administration of arecoline was used to measure E. multilocularis prevalence, trapping small mammals around communities was employed to assess the change in infection of pikas and voles, and analysis of human AE abdominal ultrasound-based data was used to understand the change in prevalence in the past decade. In all three evaluated townships, the E. multilocularis prevalence in owned dogs was significantly (P < 0.01) reduced from 7.23% (25/346) during 2000-2003 to 0.55% (1/181) in 2016. Human AE ultrasound-based prevalence (adjusted for age and sex) in five evaluated townships decreased significantly (P < 0.01) from 6.25% (200/3,198) during 2000-2002 to 3.67% (706/19,247) during 2015-2017. The 2016 prevalence of E. multilocularis metacestodes in small mammal intermediate hosts was not significantly different from the prevalence in 2008. The control programme was effective in reducing E. multilocularis infection in owned dogs and human AE prevalence, but did not significantly impact infection in wildlife intermediate hosts.