Genetic predisposition to cancers in children and adolescents.

PURPOSE OF REVIEW: Childhood cancer is rare, but it remains the leading cause of disease-related mortality among children 1-14 years of age. As exposure to environmental factors is lower in children, inherited genetic factors become an important player in the cause of childhood cancer. This review highlights the current knowledge and approach for cancer predisposition syndromes in children. RECENT FINDINGS: Current literature suggests that 10-18% of paediatric cancer patients have an underlying genetic susceptibility to their disease. With better knowledge and technology, more genes and syndromes are being discovered, allowing tailored treatment and surveillance for the probands and their families.Studies have demonstrated that focused surveillance can detect early malignancies and increase overall survival in several cancer predisposition syndromes. Various approaches have been proposed to refine early tumour detection strategies while minimizing the burden on patients and families. Newer therapeutic strategies are being investigated to treat, or even prevent, tumours in children with cancer predisposition. SUMMARY: This review summarizes the current knowledge about different cancer predisposition syndromes, focusing on the diagnosis, genetic counselling, surveillance and future directions.

Analysis of prognostic factors in patients with self-expandable metallic stents for treatment of malignant gastric outlet obstruction.

BACKGROUND AND AIM: Self-expandable metallic stents (SEMSs) are widely accepted as a less-invasive treatment for malignant gastric outlet obstruction (GOO). However, the factors related to prognosis and stent dysfunction after SEMS placement are not well known, and we aimed to investigate them. METHODS: This was a single-center retrospective cohort study of 212 malignant strictures in 207 patients. Factors related to prolonged overall survival (OS) and time to recurrent GOO (TRGOO) after SEMS placement were evaluated. RESULTS: Improvement of oral intake was confirmed in 179 patients (86%). The median OS was 65 days. A Cox proportional hazards model revealed that lower cancer stage, lower performance status score at the time of SEMS placement, and administration of chemotherapy after SEMS placement were significant predictive factors for prolonged OS. The median OS was 182 days in the group of SEMS followed by chemotherapy (group A) and 43 days in the group of SEMS alone (group B) (p< .0001). Chemotherapy after SEMS implantation contributed to the prolongation of survival in gastric cancer (hazard ratio (HR), 0.12) and pancreatic cancer (HR, 0.41). Furthermore, the cumulative incidence rates of stent dysfunction on day 120 after SEMS placement were 30% in group A and 61% in group B (p=.03). Notably, the preventive effect of chemotherapy on stent dysfunction was significant in pancreatic cancer. CONCLUSIONS: SEMS is a treatment with high technical and clinical success rate for malignant GOO. Furthermore, subsequent chemotherapy prolongs OS especially in gastric cancer, and TRGOO in pancreatic cancer.

Efficacy of polyglycolic acid sheeting with fibrin glue for perforations related to gastrointestinal endoscopic procedures: a multicenter retrospective cohort study.

OBJECTIVES: Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation. METHODS: The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated. RESULTS: There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred. CONCLUSION: Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures.

DNA methylation array analysis for diffuse leptomeningeal glioneuronal tumor with conspicuous hypothalamic mass. A case report.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare glioneuronal neoplasm newly included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Owing to the wide spectrum of its histopathological and radiological features, accurate diagnosis can be challenging. Recently, molecular testing including DNA methylation array has been introduced with the possibility of improving diagnostic accuracy and contributing to the subtyping especially for brain tumors with ambiguous histology. Two molecularly distinct subtypes of DLGNT have been reported: methylation class-1 (MC-1) with an indolent clinical course and MC-2, the latter aggressive. Herein, we report a case of a 14-year-old girl with a conspicuous hypothalamic mass lesion and diffuse leptomeningeal enhancement on magnetic resonance imaging. Biopsy specimens obtained from the hypothalamic lesion endoscopically were mainly composed of oligodendrocyte-like cells. However, it was difficult to make a definite diagnosis from these non-specific histological findings. Thus, DNA methylation array analysis was performed additionally by using formalin-fixed, paraffin-embedded tissue, resulting in a diagnosis of "MC-1 subtype of DLGNT" with a high calibrated score (0.99). Consequently, she was treated conservatively, with neither progression of the tumor nor aggravation of symptoms for the next 12 months. It was concluded that DNA methylation array analysis for DLGNT, a rare glioneuronal tumor, could be a powerful tool not only for accurate diagnosis but also decision-making in selecting the best treatment.

[Pediatric Hemispheric Glioma].

About one-third of pediatric low-grade glioma and a half of pediatric high-grade glioma occur in the cerebrum. Pediatric hemispheric glioma may harbor diagnostic and therapeutically targetable genetic abnormalities, including BRAF V600E, H3.3 G34R/V, FGFR1 alternation, MYB or MYBL1 alternation, and NTRK/ALK/ROS1/MET fusion. In addition, the efficacy of molecular-targeted agents, such as BRAF inhibitors, MEK inhibitors, and NTRK inhibitors, against pediatric glioma with the relevant mutations has been demonstrated in several clinical trials. Furthermore, checkpoint inhibitors are considered a choice of treatment for hypermutated glioma, which is typically observed in patients with constitutional mismatch repair deficiency syndrome. Cancer gene panel testing, approved for insurance coverage in Japan in 2019, has been beneficial to pediatric cancer patients. However, to promote the clinical application of the recent molecular understanding of pediatric neuro-oncology, some issues have to be addressed. Herein, we review the genetic profiles of pediatric hemispheric glioma and introduce the current medical situation of precision medicine for pediatric patients with glioma in Japan.

Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma.

The current standard of diagnosing central nervous system (CNS) lymphoma is stereotactic biopsy, however the procedure has a risk of surgical complication. Liquid biopsy of the CSF is a less invasive, non-surgical method that can be used for diagnosing CNS lymphoma. In this study, we established a clinically applicable protocol for determining mutations in MYD88 in the CSF of patients with CNS lymphoma. CSF was collected prior to the start of chemotherapy from 42 patients with CNS lymphoma and matched tumor specimens. Mutations in MYD88 in 33 tumor samples were identified using pyrosequencing. Using 10 ng each of cellular DNA and cell-free DNA (cfDNA) extracted from the CSF, the MYD88 L265P mutation was detected using digital PCR. The conditions to judge mutation were rigorously determined. The median Target/Total value of cases with MYD88 mutations in the tumors was 5.1% in cellular DNA and 22.0% in cfDNA. The criteria to judge mutation were then determined, with a Target/Total value of 0.25% as the cutoff. When MYD88 mutations were determined based on these criteria, the sensitivity and specificity were 92.2% and 100%, respectively, with cellular DNA; and the sensitivity and specificity were 100% with cfDNA. Therefore, the DNA yield, mutated allele fraction, and accuracy were significantly higher in cfDNA compared with that in cellular DNA. Taken together, this study highlights the importance of detecting the MYD88 L265P mutation in cfDNA of the CSF for diagnosing CNS lymphoma using digital PCR, a highly accurate and clinically applicable method.

Malignant brain tumor in an infant showing histopathological features of yolk sac tumor but genetic and epigenetic features of AT/RT.

SMARCA4 pathogenic variants are rarely detected in pediatric brain tumors other than atypical teratoid rhabdoid tumors (AT/RTs) without INI1 deficiency or in some cases of medulloblastoma. Here, we report an atypical intracranial immature teratoma that recurred as a yolk sac tumor with metastatic spinal and lung lesions. Sequencing of the tumor revealed two SMARCA4 variants, including a splice-site variant and a non-synonymous variant of uncertain significance. Additionally, the methylation signature of the tumor was close to that of AT/RTs. Our case might be a yet-unrecognized subtype of pediatric tumors in which inactivation of SMARCA4 contributes to the pathogenesis.

Feasibility and Safety of Endoscopic Submucosal Dissection for Recurrent Rectal Lesions that after Transanal Endoscopic Microsurgery: A Case Series.

OBJECTIVES: Recently, several studies have demonstrated the usefulness of endoscopic submucosal dissection (ESD) for residual or locally recurrent colorectal lesions after endoscopic treatment. However, the feasibility of ESD for recurrent rectal lesions after transanal endoscopic microsurgery (TEM) has not been fully investigated. In this study, we evaluated the feasibility and safety of ESD for recurrent rectal lesions after TEM. METHODS: The treatment outcomes of 10 lesions in 9 patients, who underwent ESD between January 2006 and March 2018 for recurrent rectal lesions after transanal endoscopic microsurgery, were evaluated. RESULTS: All lesions were successfully resected en bloc, and the R0 resection rate was 90%. The median size of the resected specimens and lesions (range) was 44 mm (21-70) and 27.5 mm (5-60), respectively. The pathological diagnoses included 4 adenomas and 6 cancerous lesions. The cancerous lesions included 5 cases of mucosal cancer and 1 case of superficial submucosal invasive cancer (depth of submucosal invasion <1,000 µm from the muscularis mucosae). No adverse events occurred. There was no recurrence during the follow-up period. CONCLUSIONS: ESD for recurrent rectal lesions after TEM by expert's hands appears to be safe and feasible.

Endoscopic submucosal dissection involving the anal canal presents a risk factor for postoperative stricture.

BACKGROUND: Although postoperative strictures after endoscopic submucosal dissection (ESD) in the rectum are relatively rare, some rectal lesions require resection involving the anal canal, which is a narrow tract comprising squamous epithelium. To the best of our knowledge, no studies have investigated narrow anal canals when evaluating post-ESD strictures. This study aimed to evaluate the impact of resections involving the anal canal on postoperative stricture development. METHODS: Between April 2005 and October 2017, 707 rectal lesions were treated with ESD. We retrospectively investigated 102 lesions that required ≥ 75% circumferential resection. Risk factors for post-ESD stricture and, among patients with strictures, obstructive symptoms, and number of dilation therapies required were investigated. RESULTS: Post-ESD stricture occurred in 18 of 102 patients (17.6%). In the multivariate analysis, circumferential resection ≥ 90% and ESD involving the anal canal (ESD-IAC) were risk factors for postoperative strictures (P ≤ 0.0001 and 0.0115, respectively). Among the patients with strictures, obstructive symptoms were significantly related to anal strictures compared to rectal strictures (100% vs. 27.2%, P = 0.0041). Furthermore, the number of dilation therapies required was significantly greater among patients with anal strictures compared to those with rectal strictures (6.5 times vs. 2.7 times, P = 0.0263). CONCLUSION: Not only circumferential resection ≥ 90% but also ESD-IAC was a significant risk factor for the stricture after rectal ESD. Furthermore, anal strictures were associated with a significantly higher frequency of obstructive symptoms and larger number of required dilation therapies than were rectal strictures.

Development and validation of an endoscopic submucosal dissection video assessment tool.

BACKGROUND: Despite a need for assessment of endoscopic submucosal dissection (ESD) skills in order to track progress and determine competence, there is no structured measure of assessing competency in ESD performance. The present study aims to develop and examine validity evidence for an assessment tool to evaluate the recorded performance of ESD for gastric neoplasms. METHODS: The ESD video assessment tool (EVAT) was systematically developed by ESD experienced endoscopists. The EVAT consists of a 25-item global rating scale and 3-item checklist to assess competencies required to perform ESD. Five unedited videos were each evaluated by 2-blinded experienced ESD endoscopists to assess inter-rater reliability using intraclass correlation coefficients (ICC). Seventeen unedited videos in total were rated by 3 blinded experienced ESD endoscopists. Validity evidence for relationship to other variables was examined by comparing scores of inexperienced (fellows) and experienced endoscopists (attending staff), and by evaluating the relationship between the EVAT scores and ESD case experience. Internal consistency was evaluated using Cronbach's alpha. RESULTS: The inter-rater reliability for the total score was high at 0.87 (95% confidence interval 0.11 to 0.99). The total score [median, interquartile range (IQR)] was significantly different between the inexperienced (71, 63-77) and experienced group (95, 91-97) (P = 0.005). The total scores demonstrated high correlation with the number of ESD cases (Spearman's ρ = 0.79, P < 0.01). The internal consistency was 0.97. CONCLUSIONS: This study provides preliminary validity evidence for the assessment of video-recorded ESD performances for gastric neoplasms using EVAT.

Medical guidelines for Li-Fraumeni syndrome 2019, version 1.1.

Li-Fraumeni syndrome (LFS) is a hereditary tumor that exhibits autosomal dominant inheritance. LFS develops in individuals with a pathogenic germline variant of the cancer-suppressor gene, TP53 (individuals with TP53 pathogenic variant). The number of individuals with TP53 pathogenic variant among the general population is said to be 1 in 500 to 20,000. Meanwhile, it is found in 1.6% (median value, range of 0-6.7%) of patients with pediatric cancer and 0.2% of adult patients with cancer. LFS is diagnosed by the presence of germline TP53 pathogenic variants. However, patients can still be diagnosed with LFS even in the absence of a TP53 pathogenic variant if the familial history of cancers fit the classic LFS diagnostic criteria. It is recommended that TP53 genetic testing be promptly performed if LFS is suspected. Chompret criteria are widely used for the TP53 genetic test. However, as there are a certain number of cases of LFS that do not fit the criteria, if LFS is suspected, TP53 genetic testing should be performed regardless of the criteria. The probability of individuals with TP53 pathogenic variant developing cancer in their lifetime (penetrance) is 75% for men and almost 100% for women. The LFS core tumors (breast cancer, osteosarcoma, soft tissue sarcoma, brain tumor, and adrenocortical cancer) constitute the majority of cases; however, various types of cancers, such as hematological malignancy, epithelial cancer, and pediatric cancers, such as neuroblastoma, can also develop. Furthermore, approximately half of the cases develop simultaneous or metachronous multiple cancers. The types of TP53 pathogenic variants and factors that modify the functions of TP53 have an impact on the clinical presentation, although there are currently no definitive findings. There is currently no cancer preventive agent for individuals with TP53 pathogenic variant. Surgical treatments, such as risk-reducing bilateral mastectomy warrant further investigation. Theoretically, exposure to radiation could induce the onset of secondary cancer; therefore, imaging and treatments that use radiation should be avoided as much as possible. As a method to follow-up LFS, routine cancer surveillance comprising whole-body MRI scan, brain MRI scan, breast MRI scan, and abdominal ultrasonography (US) should be performed immediately after the diagnosis. However, the effectiveness of this surveillance is unknown, and there are problems, such as adverse events associated with a high rate of false positives, overdiagnosis, and sedation used during imaging as well as negative psychological impact. The detection rate of cancer through cancer surveillance is extremely high. Many cases are detected at an early stage, and treatments are low intensity; thus, cancer surveillance could contribute to an improvement in QOL, or at least, a reduction in complications associated with treatment. With the widespread use of genomic medicine, the diagnosis of LFS is unavoidable, and a comprehensive medical care system for LFS is necessary. Therefore, clinical trials that verify the feasibility and effectiveness of the program, comprising LFS registry, genetic counseling, and cancer surveillance, need to be prepared.

Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases.

BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan. Blood and fecal samples were collected weekly and antigen-specific IgG and IgA titers were measured. Lymph nodes and spleens were collected and analyzed by enzyme-linked immunosorbent assay for antigen-specific splenic T-helper 1 cells, T-helper 17 cells, and memory B cells. Six weeks after primary immunization, mice were given a oral, nasal, or vaginal boost of ovalbumin; intestinal lamina propria, bronchial lavage, and vaginal swab samples were collected and antibodies and cytokines were measured. Some mice were also given oral cholera toxin or intranasal Streptococcus pneumoniae and the severity of diarrhea or pneumonia was analyzed. Gnotobiotic mice were gavaged with fecal material from obese individuals, which had a high abundance of Clostridium ramosum (a commensal microbe associated with obesity and diabetes), and were placed on a high-fat diet 2 weeks after immunization with C ramosum. Intestinal tissues were collected and analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum and fecal samples from mice given injections of antigens in combination with CpG oligodeoxynucleotides and curdlan for 3 weeks contained antigen-specific IgA and IgG, and splenocytes produced interferon-gamma and interleukin 17A. Lamina propria, bronchial, and vaginal samples contained antigen-specific IgA after the ovalbumin boost. This immunization regimen prevented development of diarrhea after injection of cholera toxin, and inhibited lung colonization by S pneumoniae. In gnotobiotic mice colonized with C ramosum and placed on a high-fat diet, the mice that had been immunized with C ramosum became less obese than the nonimmunized mice. CONCLUSIONS: Injection of mice with microbial antigens and adjuvant induces antigen-specific mucosal and systemic immune responses. Immunization with S pneumoniae antigen prevented lung infection by this bacteria, and immunization with C ramosum reduced obesity in mice colonized with this microbe and placed on a high-fat diet. This immunization approach might be used to protect against microbe-associated disorders of intestine.

[A Case of Familial Schwannomatosis Occurring as Intraorbital Schwannoma].

A 67-year-old male presenting with left exophthalmos and progressive visual disturbance was referred to our department. Tumors at the supraclavicular fossa and dorsal femoral region were resected at ages 27 and 45 years. His father and son had both been diagnosed with spinal tumors, and his son's tumor was pathologically diagnosed as a schwannoma. Brain MRI of his son demonstrated no intracranial tumor. Brain MRI of the patient revealed a multilobular tumor of 2 cm diameter compressing the optic nerve medially within the left muscle cone, and no other intracranial tumors. However, large masses lateral to the pharynx and intercostal nerve, as well as multiple spinal tumors were detected. Transcranial total resection of the intraorbital tumor was performed. The pathological diagnosis was consistent with a schwannoma. These clinical characteristics fulfilled the diagnostic criteria of familial schwannomatosis. The postoperative course was uneventful. His visual dysfunction and eye movement disorder resolved completely. The intraorbital tumor was believed to originate from the lacrimal nerve. Sequencing of all exons for SMARCB1 and LZTR1 using DNA extracted from the tumor did not reveal any mutations. This case is the third report on familial schwannomatosis in Japan.

Genome-wide DNA methylation profiling shows molecular heterogeneity of anaplastic pleomorphic xanthoastrocytoma.

In the revised World Health Organization classification 2016, anaplastic pleomorphic xanthoastrocytoma (PXA) has been newly defined as a variant of the PXA entity. Furthermore, some anaplastic PXA were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome-wide molecular analysis, we show an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA.

Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone.

Giant cell tumor of bone typically involves the epiphysis of the long bones of skeletally mature patients. It is genetically characterized by highly recurrent and specific mutations of the H3F3A gene, which encodes histone H3.3. The most common mutation H3F3A G34W can readily be detected by a recently developed mutation-specific antibody. Giant cell tumor of bone rarely transforms to a sarcoma (malignant giant cell tumor of bone), which has not been genetically characterized in detail. We studied seven clinicopathologically defined malignant giant cell tumors, as well as two H3F3A-mutant bone sarcomas without giant cell tumor histology using a combination of clinicopathological, immunohistochemical, and molecular methods (Sanger sequencing + pyrosequencing or next generation sequencing). The cases included five men and four women, with a median age at initial diagnosis of 27 years. The two H3F3A G34W-positive sarcomas without giant cell tumor histology involved the subarticular epiphyseal sites, suggesting relatedness with giant cell tumor of bone. In two of the seven clinicopathologically defined malignant giant cell tumor cases, the sarcoma tissue showed the H3F3A G34W mutation. However, in the remaining five cases, in contrast to their associated H3F3A G34W-mutant giant cell tumor, the sarcoma lacked the H3F3A G34W mutation, either entirely or sub-clonally in the samples tested. This discordant mutation status was confirmed in all instances by immunohistochemistry and sequencing. A FISH analysis suggested that the absence of the H3F3A G34W mutation may be related to deletion of the H3F3A gene. Therefore, we have demonstrated that H3F3A G34W mutation, a critical driver in giant cell tumor, is absent in a subset of malignant giant cell tumor of bone. This novel recurrent phenomenon has potential biological and diagnostic implications, and further study is required to better characterize this progression pathway and understand its mechanism.

Presacral malignant teratoid neoplasm in association with pathogenic DICER1 variation.

We report two malignant sacrococcygeal tumors in infants that were associated with pathogenic DICER1 variation. These tumors were composed of primitive neuroepithelium, embryonal rhabdomyosarcoma, and cartilage and initially diagnosed as immature teratomas. One child developed intracranial metastasis and died. The second child underwent surgery and chemotherapy and achieved complete remission. This child subsequently developed five additional DICER1-associated neoplasms by age nine. Genetic analysis revealed that both tumors harbored biallelic pathogenic DICER1 variation. We believe these cases represent another novel subtype of DICER1-associated tumor. This new entity, which we propose to call DICER1-associated presacral malignant teratoid neoplasm, may be difficult initially to distinguish from immature teratoma, but recognizing it as an entity can prompt appropriate classification as an aggressive malignancy and facilitate appropriate genetic counseling, DICER1 germline variant testing, screening, and education.

Successful treatment of metastatic cerebral recurrence of pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare pediatric tumor. The central nervous system (CNS) is the most common site of extrathoracic metastasis. The prognosis of PPB patients with CNS metastases is dismal: most patients die within one year after recurrence. Here, we describe two patients diagnosed with PPB who developed intracranial recurrences shortly after the end of their initial treatment and were successfully treated by gross total resection, radiotherapy, and chemotherapy. Both patients are in complete remission four and three years after recurrence. Although an optimal regimen remains to be determined, these cases demonstrate that PPB with CNS metastases is potentially curable.

Endoscopic plombage with polyglycolic acid sheets and fibrin glue for gastrointestinal fistulas.

BACKGROUND AND STUDY AIMS: Gastrointestinal (GI) fistulas arise as adverse events of GI surgery and endoscopic treatment as well as secondary to underlying diseases, such as ulceration and pancreatitis. Until a decade ago, they were mainly treated surgically or conservatively. Bioabsorbable polyglycolic acid (PGA) sheets and fibrin glue, which are commonly used in surgical procedures, have also recently been used in endoscopic procedures for the closure of GI defects. However, there have only been few case reports about successful experiences with this approach. There have not been any case-series studies investigating the strengths and weaknesses of such PGA sheet-based treatment. In this study, we evaluated the clinical effectiveness of using PGA sheets to close GI fistulas. PATIENTS AND METHODS: Cases in which patients underwent endoscopic filling with PGA sheets and fibrin glue for GI fistulas at Kobe University Hospital between January 2013 and April 2018 were retrospectively reviewed. RESULTS: A total of 10 cases were enrolled. They included fistulas due to leakage after GI surgery, aortoesophageal/bronchoesophageal fistulas caused by chemoradiotherapy, or severe acute pancreatitis. The fistulas were successfully closed in 7 cases (70%). The unsuccessful cases involved a fistula due to leakage after surgical esophagectomy and bronchoesophageal fistulas due to chemoradiotherapy or severe acute pancreatitis. Unsuccessful treatment was related to fistula epithelization. CONCLUSION: Endoscopic plombage with PGA sheets and fibrin glue could be a promising therapeutic option for GI fistulas.

Defining competencies for endoscopic submucosal dissection (ESD) for gastric neoplasms.

BACKGROUND: Current methods for teaching and assessing competencies for endoscopic submucosal dissection (ESD) are highly variable, non-systematic, and are inefficient for the learner to acquire adequate skills. The present study aims to define and establish expert consensus regarding competencies required to perform ESD for gastric neoplasms. METHODS: Fourteen ESD experts from 12 institutions in Japan were invited to complete an online survey to rate potential items for their importance in performing ESD proficiently. By using methodology based on the Delphi principles, the results of each round were analyzed and re-sent to the experts until consensus was established. Items were included if ranked 8 out of a 10-point Likert scale, by ≥ 80% of the respondents. RESULTS: A list of 29 potential items was generated through a review of the literature, textbooks, and experience of the steering group members. Ten new items were added through the survey. Consensus was reached after three rounds. Response rate ranged from 93 to 100%. Thirty-four items achieved consensus as important surrogates of competency in performing ESD. CONCLUSIONS: Essential competencies for performing ESD were identified through expert consensus. These competencies can serve as the foundation for structured training and for development of objective assessment tools to evaluate trainee performance in ESD.