Underwater versus conventional EMR for nonpedunculated colorectal lesions: a randomized clinical trial.

BACKGROUND AND AIMS: Conventional endoscopic mucosal resection (CEMR) is the standard modality for removing nonpedunculated colorectal lesions. Underwater endoscopic mucosal resection (UEMR) has emerged as an alternative method. There are few comparative studies between these techniques, especially evaluating recurrence. Therefore, the purpose of this trial was to compare CEMR and UEMR for the resection of colorectal lesions with respect to efficacy, safety, and recurrence rate. METHODS: This was a randomized controlled trial of UEMR versus CEMR for naïve and nonpedunculated lesions measuring between 10 and 40 mm. The primary outcome was adenoma recurrence at 6 months after the resection. Secondary outcomes were rates of technical success, en bloc resection, and adverse events. Block randomization was used to assign patients. Tattooing was performed to facilitate localization of the scars and eventual recurrences. Endoscopic follow-up was scheduled at 6 months after the procedure. The sites of resections were examined with white-light imaging, narrow-band imaging (NBI), and conventional chromoscopy with indigo carmine followed by biopsies. RESULTS: One hundred five patients with 120 lesions were included, with a mean size of 17.5 ± 7.1 (SD) mm. Sixty-one lesions were resected by UEMR and 59 by CEMR. The groups were similar at baseline regarding age, sex, average size, and histologic type. Lesions in the proximal colon in the CEMR group corresponded to 83% and in the UEMR group to 67.8% (P = .073). There was no difference between groups regarding success rate (1 failure in each group) and en bloc resection rate (60.6% UEMR vs 54.2% CEMR, P = .48). Intraprocedural bleeding was observed in 5 CEMRs (8.5%) and 2 UEMRs (3.3%) (P = .27). There was no perforation or delayed hemorrhage in either groups. Recurrence rate was higher in the CEMR arm (15%) than in the UEMR arm (2%) (P = .031). Therefore, the relative risk of 6-month recurrence rate in the CEMR group was 7.5-fold higher (95% CI, 0.98-58.20), with a number needed to treat of 7.7 (95% CI, 40.33-4.22). The higher recurrence rate in the CEMR group persisted only for lesions measuring 21 to 40 mm (35.7% vs 0%; P = .04). CONCLUSION: This study demonstrated that UEMR was associated with a lower adenoma recurrence rate than was CEMR. Both endoscopic techniques were effective and had similar rates of adverse events for the treatment of nonpedunculated colorectal lesions.

Tube-in-tube endoscopic vacuum therapy for treatment of colorectal anastomotic leaks: A low-cost, patient-friendly, feasible and efficient technical modification of sponge-based endoscopic vacuum therapy.

BACKGROUND AND AIMS: Colorectal endoscopic vacuum therapy (CR EVT) is usually performed using sponges passed through the anus. It may be associated with patient discomfort and displacement of the aspiration tube. METHODS: With the tube-in-tube endoscopic vacuum therapy modification (CR TT-EVT), it is possible to position the aspiration tube in the pelvic cavity through the abdominal wall. In addition, it allows frequent cleaning of the fistula, eliminates the need for programmed device changes, and enables a standardized approach to such a wide variety of fistulas, leaks, and perforations. RESULTS: Here is a technical note on how to perform CR TT-EVT, while we are at the early phase of our case series we have reached 100% of technical success.

Tube-in-tube endoscopic vacuum therapy for the closure of upper gastrointestinal fistulas, leaks, and perforations.

BACKGROUND : Although endoscopic vacuum therapy (EVT) has been successfully used to treat postoperative upper gastrointestinal (UGI) wall defects, its use demands special materials and several endoscopic treatment sessions. Herein, we propose a technical modification of EVT using a double tube (tube-in-tube drain) without polyurethane sponges for the drainage element. The tube-in-tube drainage device enables irrigation and application of suction. A flowchart for standardizing the management of postoperative UGI wall defects with this device is presented. METHODS : An EVT modification was made to achieve frequent fistula cleansing, with 3 % hydrogen peroxide rinsing, and the application of negative pressure. A tube-in-tube drain without polyurethane sponges can be inserted like a nasogastric tube or passed through a previously positioned surgical drain. This was a retrospective two-center observational study, with data collected from 30 consecutive patients. Technical success, clinical success, adverse events, time under therapy, interval time from procedure to fistula diagnosis and treatment start, size of transmural defect, volume of cavity, number of endoscopic treatment sessions, and mortality were reviewed. RESULTS : 30 patients with UGI wall defects were treated. The technical and clinical success rates were 100 % and 86.7 %, respectively. Three patients (10 %) had adverse events and three patients (10 %) died. The median time under therapy was of 19 days (range 1-70) and the median number of endoscopic sessions was 3 (range 1-9). CONCLUSIONS : This standardized approach and EVT modification using a tube-in-tube drain, with frequent fistula cleansing, were successful and safe in a wide variety of UGI wall defects.

New anti-angiogenic compound based on chemically modified heparin.

PURPOSE: The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re-N-acetylated, a chemically modified heparin (mHep). METHODS: In vitro assays (cell tube formation, viability, proliferation, and migration) with endothelial cells were performed after 24 h of treatment with mHep at 10, 100, and 1000 ng/mL or saline. In vivo tests were performed after laser-induced choroidal neovascularization (CNV) in rats, followed by an intravitreal injection (5 µL) of mHep (10, 100, 1000 ng/mL) or balanced salt solution. Immunofluorescence analysis of the CNV was performed after 14 days. RESULTS: mHep produced a statistically significant reduction in cell proliferation, tube formation, and migration, without cell viability changes when compared to saline. Mean measures of CNV area were 54.84 × 106 pixels/mm (± 12.41 × 106), 58.77 × 106 pixels/mm (± 17.52 × 106), and 59.42 × 106 pixels/mm (± 17.33 × 106) in groups 100, 1000, and 10,000 ng/mL, respectively, while in the control group, mean area was 72.23 × 106 (± 16.51 × 106). The P value was 0.0065. Perimeter analysis also demonstrated statistical significance (P = 0.0235) with the mean measure of 93.55 × 104, 94.23 × 104, and 102 × 104 in the 100 ng/mL, 1000 ng/mL, and control groups, respectively. CONCLUSIONS: These results suggest that mHep N-DRN is a potent anti-angiogenic, anti-proliferative, and anti-migratory compound with negligible anticoagulant or hemorrhagic action and no cytotoxicity for retina cells. This compound may serve as a candidate for treating choroidal neovascularization.

A virulent and pathogenic infectious clone of Senecavirus A.

Senecavirus A (SVA) is a picornavirus that circulates in swine populations worldwide causing vesicular disease (VD) in affected animals. Here we developed a reverse genetics system for SVA based on the well-characterized wild-type SVA strain SD15-26 (wt SVA SD15-26). The full-length cDNA genome of SVA was cloned into a plasmid under a T7 RNA polymerase promoter. Following in vitro transcription, the genomic viral RNA was transfected into BHK-21 cells and rescue of infectious virus (rSVA SD15-26) was shown by inoculation of highly susceptible H1299 cells. In vitro characterization of the rSVA SD15-26 showed similar replication properties and protein expression levels as the wt SVA SD15-26. A pathogenesis study was conducted in 15-week-old finishing pigs to evaluate the pathogenicity and infection dynamics of the rSVA SD15-26 virus in comparison to the wt SVA SD15-26. Animals from both rSVA- and wt SVA SD15-26-inoculated groups presented characteristic SVA clinical signs (lethargy and lameness) followed by the development of vesicular lesions on the snout and/or feet. The clinical outcome of infection, including disease onset, severity and duration was similar in rSVA- and the wt SVA SD15-26-inoculated animals. All animals inoculated with rSVA or with wt SVA SD15-26 presented a short-term viremia, and animals from both groups shed similar amounts of virus in oral and nasal secretion, and faeces. Our data demonstrates that the rSVA SD5-26 clone is fully virulent and pathogenic in pigs, presenting comparable pathogenesis and infection dynamics to the wt SVA SD15-26 strain. The infectious clone generated here is a useful platform to study virulence determinants of SVA, and to dissect other aspects of SVA infection biology, pathogenesis and persistence.

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex.

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of α-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of ß-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration.

Adaptive Immune Responses following Senecavirus A Infection in Pigs.

Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust virus-neutralizing (VN) antibody response, which coincided and was strongly correlated with VP2- and VP3-specific IgM responses. Notably, the neutralizing antibody (NA) responses paralleled the reduction of viremia and resolution of the disease. Analysis of the major porcine T-cell subsets revealed that during the acute/clinical phase of SVA infection (14 days postinfection [p.i.]), T-cell responses were characterized by an increased frequency of αß T cells, especially CD4+ T cells, which were first detected by day 7 p.i. and increased in frequency until day 14 p.i. Additionally, the frequency of CD8+ and double-positive CD4+ CD8+ T cells (effector/memory T cells) expressing interferon gamma (IFN-γ) or proliferating in response to SVA antigen stimulation increased after day 10 p.i. Results presented here show that SVA elicits B- and T-cell activation early upon infection, with IgM antibody levels being correlated with early neutralizing activity against the virus and peak B- and T-cell responses paralleling clinical resolution of the disease. The work provides important insights into the immunological events that follow SVA infection in the natural host.IMPORTANCE Senecavirus A (SVA) has recently emerged in swine, causing outbreaks of vesicular disease (VD) in major swine-producing countries around the world, including the United States, Brazil, China, Thailand, and Colombia. Notably, SVA-induced disease is clinically indistinguishable from other high-consequence VDs of swine, such as FMD, swine vesicular disease, vesicular stomatitis, and vesicular exanthema of swine. Despite the clinical relevance of SVA-induced VD, many aspects of the virus infection biology remain unknown. Here, we assessed host immune responses to SVA infection. The results show that SVA infection elicits early B- and T-cell responses, with the levels of VN antibody and CD4+ T-cell responses paralleling the reduction of viremia and resolution of the disease. SVA-specific CD8+ T cells are detected later during infection. A better understanding of SVA interactions with the host immune system may allow the design and implementation of improved control strategies for this important pathogen of swine.

Clinical and endoscopic aspects of metastases to the gastrointestinal tract.

BACKGROUND: Studies that describe metastases to the gastrointestinal (GI) tract are restricted to small case series. An increase in the frequency of this condition is expected, so it would be useful to better characterize the endoscopic aspects of metastasis to the GI tract. The aims of this study were to describe the frequency and endoscopic features of the lesions, and to analyze the survival rate after diagnosis of metastasis. METHODS: This was a retrospective, single-center, observational study, conducted between 2009 and 2017. Patients with metastasis to the GI tract were included. RESULTS: 95 patients were included. Melanoma (25.3 %), lung (15.8 %), and breast (14.7 %) were the most frequent primary tumors. The most common endoscopic presentation was a solitary, ulcerated lesion in the gastric body. Conventional biopsy was diagnostic in 98.9 % of the cases. The mean and median survival rates were 13.3 months (95 % confidence interval [CI] 8.2 - 18.3) and 4.7 months (95 %CI 3.7 - 5.6), respectively. Palliative treatment with chemo- and/or radiotherapy after the diagnosis of the metastasis was related to a higher survival rate. CONCLUSIONS: Melanoma, lung, and breast cancer were the most common primary tumors to metastasize to the GI tract. The endoscopic features could not predict the primary site of the tumor. The finding of metastasis in the GI tract is related to the final stage of the cancer disease but patients who received palliative treatment with chemo- and/or radiotherapy after diagnosis of GI metastasis had higher survival rates.

Self-expandable metal stent for malignant esophagorespiratory fistula: predictive factors associated with clinical failure.

BACKGROUND AND AIMS: Malignant esophagorespiratory fistulas (MERFs) usually are managed by the placement of self-expandable metal stents (SEMSs) but with conflicting results. This study aimed to identify risk factors associated with clinical failure after SEMS placement for the treatment of MERFs. METHODS: This was a retrospective analysis of a prospectively maintained database used at a tertiary-care cancer hospital, with patients treated with SEMS placement for MERFs between January 2009 and February 2016. Logistic regression was used to identify predictive factors for clinical outcomes and to estimate the odds ratio (OR) and the 95% confidence interval (CI). The Kaplan-Meier method was used for survival analysis, and comparisons were made by using the log-rank test. RESULTS: A total of 71 patients (55 male, mean age 59 years) were included in the study, and 70 were considered for the final analysis (1 failed stent insertion). Clinical failure occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 and fistula development during esophageal cancer treatment were associated with an increased risk of clinical failure. ECOG status of 3 or 4, pulmonary infection at the time of SEMS placement, and prior radiation therapy were predictive factors associated with lower overall survival. Dysphagia scores improved significantly 15 days after stent insertion. The overall stent-related adverse event rate was 30%. Stent migration and occlusion caused by tumor overgrowth were the most common adverse events. CONCLUSION: SEMS placement is a reasonable treatment option for MERFs; however, ECOG status of 3 or 4 and fistula development during esophageal cancer treatment may be independent predictors of clinical failure after stent placement.

Probe-based confocal endomicroscopy is accurate for differentiating gastric lesions in patients in a Western center.

OBJECTIVE: Probe-based confocal laser endomicroscopy (pCLE) technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and microvascular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric lesions. METHODS: Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE results. RESULTS: Patients' mean age was 68.3 (range, 42-83) years and six were men. Thirteen suspicious flat or elevated lesions (classified as 0-Is, 0-IIa or 0-IIa + IIc) and seven pre-malignant lesions (atrophy and intestinal metaplasia) were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body (n=10 lesions), the antrum (n=9) and the incisura angularis (n=1). All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% (19/20 lesions). CONCLUSIONS: pCLE is accurate for real time histology of gastric lesions. pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

Diagnostic accuracy of probe-based confocal laser endomicroscopy in Lugol-unstained esophageal superficial lesions of patients with head and neck cancer.

BACKGROUND AND AIMS: Surveillance programs of patients with head and neck cancer (HNC) detect synchronous or metachronous esophageal squamous cell carcinoma (ESCC) in up to 15% of patients. Noninvasive, probe-based confocal laser endomicroscopy (pCLE) technique may improve the diagnosis allowing acquisition of high-resolution in vivo images at the cellular and microvascular levels. The aim of this study was to evaluate the accuracy of pCLE for the differential diagnosis of nonneoplastic and neoplastic Lugol-unstained esophageal lesions in patients with HNC. METHODS: Twenty-seven patients with HNC who exhibited Lugol-unstained esophageal lesions at surveillance endoscopy were prospectively included for pCLE. Diagnostic pCLE was followed by subsequent biopsies or endoscopic resection of suspected lesions. A senior pathologist was blinded to the pCLE results. RESULTS: Patients mean age was 59 years (SD = 8.8) and 70.4% were men. All patients were smokers, and 22 patients (81.5%) had a history of alcohol consumption. The locations of HNC were oral cavity (n = 13), larynx (n = 10), and pharynx (n = 4). Thirty-seven lesions in 27 patients were studied. The final diagnoses were ESCC in 17 patients and benign lesions in 20 patients. Sensitivity, specificity, and accuracy of pCLE for the histologic diagnosis of ESCC in patients with HNC were 94.1%, 90.0%, and 91.9%, respectively. CONCLUSIONS: First, pCLE is highly accurate for real-time histology of Lugol-unstained esophageal lesions in patients with HNC. Second, pCLE may alter the management of patients under surveillance for ESCC, guiding biopsies and endoscopic resection, avoiding further diagnostic workup or therapy of benign lesions.

Endoscopic submucosal dissection versus transanal endoscopic microsurgery for the treatment of early rectal cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are minimally invasive procedures that can be used to treat early rectal cancer. OBJECTIVE: The aim of this study was to compare clinical efficacy between ESD and TEM for the treatment of early rectal cancer. METHODS: Between July 2008 and August 2011, 24 patients with early rectal cancers were treated by ESD (11) or TEM (13) at the Cancer Institute of São Paulo University Medical School (São Paulo, Brazil). Data were analyzed retrospectively according to database and pathological reports, with respect to en bloc resection rate, local recurrence, complications, histological diagnosis, procedure time and length of hospital stay. RESULTS: En bloc resection rates with free margins were achieved in 81.8 % of patients in the ESD group and 84.6 % of patients in the TEM group (p = 0.40). Mean tumor size was 64.6 ± 57.9 mm in the ESD group and 43.9 ± 30.7 mm in the TEM group (p = 0.13). Two patients in the TEM group and one patient in the ESD group had a local recurrence. The mean procedure time was 133 ± 94.8 min in the ESD group and 150 ± 66.3 min in the TEM group (p = 0.69). Mean hospital stay was 3.8 ± 3.3 days in the ESD group and 4.08 ± 1.7 days in the TEM group (p = 0.81). LIMITATIONS: This was a non-randomized clinical trial with a small sample size and selection bias in treatment options. CONCLUSION: ESD and TEM are both safe and effective for the treatment of early rectal cancer.

Larval morphology and advertisement call of Phyllodytes acuminatus Bokermann, 1966 (Anura: Hylidae) from Northeastern Brazil.

This paper describes the tadpole and advertisement call of Phyllodytes acuminatus, based on specimens from the Parque Nacional do Catimbau, in the municipality of Buíque, State of Pernambuco, Northeastern Brazil. The overall morphology of P. acuminatus tadpole is similar to that of most species of the genus. The presence of a double row of marginal papillae surrounding all the oral apparatus (except on most of the upper labium which has a dorsal gap) was a characteristic that differentiate P. acuminatus from the other species of the genus. Furthermore, the call structure of the species (unpulsed notes with harmonic structure) fits it in the group composed of P. kautskyi and P. melanomystax.

Analysis of Factors Related to the Success of Pediatric Kidney Transplantation: A 35 Years Experience.

BACKGROUND: Despite the significant improvement results over the past 20 years, pediatric kidney transplantation remains a challenge. Chronic rejection, thrombosis, and recurrence of the primary disease are frequent causes of graft loss that have been little studied. Therefore, our objective is to analyze factors related to a better prognosis, which can be used to improve future strategies to allow higher pediatric transplant success rates. METHODS: A retrospective cohort study with patients under 15 years old submitted for kidney transplantation at the Hospital das Clínicas da UNICAMP between January 1, 1987, and January 1, 2022. Age, patient weight, time and type of dialysis, use of anticoagulation, complications, ischemia time, and donor weight were analyzed and related to graft loss. The significance level adopted for the statistical tests was 5%. RESULTS: One hundred ninety-two medical records were anaThe mean follow-up time was 11 years, and the mean graft duration was ration 8.5 years. The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Thrombosis presented significantly with the donor's body mass index and second transplantation. There was no correlation between the analyzed variables and chronic dysfunction or acute cellular rejection. DISCUSSION: Thrombosis remains the main cause of early graft loss, followed by acute cellular rejection. Measures such as thrombophilia screening and thromboprophylaxis have been proposed to improve results. However, they are still not standardized. CONCLUSION: The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Only the thrombosis was related to the donor's body mass index and a second transplantation.

Nature Forest Reserves in Tanzania and their importance for conservation.

Since 1997 Tanzania has undertaken a process to identify and declare a network of Nature Forest Reserves (NFRs) with high biodiversity values, from within its existing portfolio of national Forest Reserves, with 16 new NFRs declared since 2015. The current network of 22 gazetted NFRs covered 948,871 hectares in 2023. NFRs now cover a range of Tanzanian habitat types, including all main forest types-wet, seasonal, and dry-as well as wetlands and grasslands. NFRs contain at least 178 of Tanzania's 242 endemic vertebrate species, of which at least 50% are threatened with extinction, and 553 Tanzanian endemic plant taxa (species, subspecies, and varieties), of which at least 50% are threatened. NFRs also support 41 single-site endemic vertebrate species and 76 single-site endemic plant taxa. Time series analysis of management effectiveness tracking tool (METT) data shows that NFR management effectiveness is increasing, especially where donor funds have been available. Improved management and investment have resulted in measurable reductions of some critical threats in NFRs. Still, ongoing challenges remain to fully contain issues of illegal logging, charcoal production, firewood, pole-cutting, illegal hunting and snaring of birds and mammals, fire, wildlife trade, and the unpredictable impacts of climate change. Increased tourism, diversified revenue generation and investment schemes, involving communities in management, and stepping up control measures for remaining threats are all required to create a network of economically self-sustaining NFRs able to conserve critical biodiversity values.