Mechanisms and therapeutic implications of hypermutation in gliomas.

A high tumour mutational burden (hypermutation) is observed in some gliomas1-5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood. Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide. Experimentally, the mutational signature of post-treatment hypermutated gliomas was recapitulated by temozolomide-induced damage in cells with MMR deficiency. MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade. Moreover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, single-cell whole-genome sequencing analysis of post-treatment hypermutated glioma cells identified microsatellite mutations. These results show that chemotherapy can drive the acquisition of hypermutated populations without promoting a response to PD-1 blockade and supports the diagnostic use of mutational burden and signatures in cancer.

"Transanal endoscopic microsurgery" with a flexible colonoscope (F-TEM): a new endoscopic treatment for suspicious deep submucosal invasion T1 rectal carcinoma.

BACKGROUND: Endoscopic techniques allow resections of deep submucosal invasion rectal carcinoma, but mostly are facing issues such as costs, follow-up care or size limit. Our aim was to design a new endoscopic technique, which retains the advantages over surgical resections while eliminating the disadvantages mentioned above. PATIENTS AND METHODS: We propose a technique for the resection of the superficial rectal tumours, with highly suspicious deep submucosal invasion. It combines steps of endoscopic submucosal dissection, muscular resection and edge-to-edge suture of the muscular layers, finally performing the equivalent of a "transanal endoscopic microsurgery" with a flexible colonoscope (F-TEM). RESULTS: A 60-year-old patient was referred to our unit, following the discovery of a 15 mm distal rectum adenocarcinoma. The computed tomography and the endoscopic ultrasound examination revealed a T1 tumour, without secondary lesions. Considering that the initial endoscopic evaluation highlighted a depressed central part of the lesion, with several avascular zones, an F-TEM was performed, without severe complication. The histopathological examination revealed negative resection margins, without risk factors for lymph node metastasis, no adjuvant therapy being proposed. CONCLUSION: F-TEM allows endoscopic resection of highly suspicious deep submucosal invasion T1 rectal carcinoma and it proves to be a feasible alternative to surgical resection or other endoscopic treatments as endoscopic submucosal dissection or intermuscular dissection.

Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy.

AIMS/HYPOTHESIS: We report the case of a woman who underwent a partial pancreatectomy for a serous cystadenoma when aged 56 years. She had been diagnosed with diabetes 6 years before and had Hashimoto's thyroiditis. Despite positive anti-GAD autoantibodies (GADA) and previous surgery, she was transiently weaned off long-acting insulin. Blood glucose levels remained well controlled with low-dose long-acting insulin. Insulin needs eventually increased 8 years after surgery, in conjunction with anti-zinc transporter 8 (ZnT8) seroconversion and decreasing residual C-peptide. We hypothesised that the surgical pancreas specimens and blood autoimmune T cell responses may provide correlates of this indolent clinical course. METHODS: Beta and alpha cell area and insulitis were quantified on pancreas head tissue sections obtained at surgery. Blood T cell responses against beta cell antigens were analysed by enzyme-linked immunospot. RESULTS: Pancreas sections displayed reduced beta cell and normal alpha cell area (0.27% and 0.85% of section area, respectively). High-grade insulitis was observed, mostly in insulin-containing islets, with a peri-insulitis pattern enriched in T cells positive for regulatory forkhead box protein 3 (FOXP3). In vitro challenge with beta cell antigens of circulating T cells collected 4 and 9 years after surgery revealed dominant and persistent IL-10 responses; IFN-γ responses increasing at 9 years, after anti-ZnT8 seroconversion, was observed. CONCLUSIONS/INTERPRETATION: Despite persistent GADA and the histopathological finding of insulitis and decreased beta cell area 6 years after diabetes diagnosis, glycaemic control was maintained with low-dose insulin up to 8 years after surgery. Regulated T cell responses towards beta cell antigens and FOXP3-positive peri-insulitis suggest spontaneous long-term regulation of islet autoimmunity after substantial beta cell loss, and eventual autoimmune progression upon anti-ZnT8 seroconversion.

Prevention of esophageal stricture after circumferential endoscopic submucosal dissection using a modified self-assembling peptide.

Circumferential endoscopic resection (ER) of the esophageal mucosa could find its place in the treatment of dysplastic Barrett's esophagus or extensive squamous cell neoplasia. However, the occurrence of esophageal strictures remains a major complication after ER exceeding 75% of the circumference. The aim of this study was to assess the effect of a modified, pH = 2, self-assembling peptide matrix (4[Arg-Ala-Asp-Ala]) (SAP) on the development of esophageal stricture after circumferential ER in a swine model. We performed a circumferential ER in 35 swine under general anesthesia. Five animals were included in the control group, 11 animals received the SAP matrix immediately after the resection, and 11 received the SAP matrix associated to a local steroid immediately after the resection. Follow-up endoscopy and esophagogram were performed before slaughter and necropsy at day 14. Eight treated animals were kept alive until day 28. At day 14, 27% of the animals in the SAP group developed a symptomatic stricture versus 100% in the control group (P = 0.008) and 50% in the SAP-triamcinolone group (P = 0.11). Application of an SAP matrix after circumferential ER in the swine allowed a significant reduction of the incidence of symptomatic stricture at day 14. Adding triamcinolone brought no significant improvement.

Diffusion-weighted imaging of the prostate: should we use quantitative metrics to better characterize focal lesions originating in the peripheral zone?

PURPOSE: To compare inter-reader concordance and accuracy of qualitative diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for the diagnosis of peripheral zone prostate cancer. MATERIALS AND METHODS: Two radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74 patients (64.3±5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men). A standardised ADCmean and nine ADC-derived parameters were measured, including ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror-ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were the reference for tumours and benign foci, respectively. Inter-reader agreement was assessed by the Cohen-kappa-coefficient and the intraclass correlation coefficient (ICC). Univariate-multivariate regressions determined the most predictive factor for cancer. RESULTS: Fifty lesions were malignant. Inter-reader concordance was fair for qualitative assessment, but excellent for quantitative assessment for all quantitative variables. At univariate analysis, ADCmean, WP-ADCratio and WL-ADCmean performed equally, but significantly better than the mirror-ADCratio (p<0.001). At multivariate analysis, the only independent variable significantly associated with malignancy was the whole-prostate-ADCratio. At a cut-off value of 0.68, sensitivity was 94-90 % and specificity was 60-38 % for readers 1 and 2, respectively. CONCLUSION: The whole-prostate-ADCratio improved the qualitative inter-reader concordance and characterisation of focal PZ-lesions. KEY POINTS: • Inter-reader concordance of DW PI-RADSv2.0 score for PZ lesions was only fair. • Using a standardised ADCmean measurement and derived DW-quantitative parameters, concordance was excellent. • The whole-prostate ADCratio performed significantly better than the mirror-ADCratio for cancer detection. • At a cut-off of 0.68, sensitivity values of WP-ADCratio were 94-90 %. • The whole-prostate ADCratio may circumvent variations of ADC metrics across centres.

Gleason Score Determination with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Guided Prostate Biopsies--Are We Gaining in Accuracy?

PURPOSE: We evaluated the accuracy of prostate magnetic resonance imaging- transrectal ultrasound targeted biopsy for Gleason score determination. MATERIALS AND METHODS: We selected 125 consecutive patients treated with radical prostatectomy for a clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to PI-RADS™ score. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. Factors associated with determining the accuracy of Gleason score on targeted biopsy were statistically assessed. RESULTS: Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Multiparametric magnetic resonance imaging detected 151 suspicious areas. Of these areas targeted biopsy showed 126 cancer foci in 115 patients, and detected the index lesion in all of them. The primary Gleason grade, secondary Gleason grade and Gleason score of the 126 individual tumors were determined accurately in 114 (90%), 75 (59%) and 85 (67%) cases, respectively. Maximal Gleason score was determined accurately in 80 (70%) patients. Gleason score determination accuracy on targeted biopsy was significantly higher for low Gleason and high PI-RADS score tumors. CONCLUSIONS: Magnetic resonance imaging-transrectal ultrasound targeted biopsy allowed for an accurate estimation of Gleason score in more than two-thirds of patients. Gleason score misclassification was mostly due to a lack of accuracy in the determination of the secondary Gleason grade.

Real-time cancer diagnosis during prostate biopsy: ex vivo evaluation of full-field optical coherence tomography (FFOCT) imaging on biopsy cores.

OBJECTIVES: To evaluate the diagnostic accuracy (Acc) of full-field optical coherence tomography (FFOCT) for cancer detection on prostate biopsy. MATERIALS AND METHODS: Thirty-eight consecutive patients with elevated PSA and/or suspicious digital rectal examination were prospectively included. For each patient, 1-10 cores were randomly selected and imaged with FFOCT immediately after sampling. The images obtained were de-identified and analyzed by three pathologists blinded to the results of pathological evaluation. The overall average Acc was measured, as well as sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV). The Acc learning curve was assessed by multivariate logistic regression, and inter-reader concordance was assessed by Kappa index. RESULTS: One hundred and nineteen cores were imaged. Of them, 40 (33.6%) were involved with cancer. The overall average Acc of FFOCT for cancer detection was of 70.6%. Se, Sp, PPV, and NPV were of 63, 74, 55.5, and 80%, respectively. A substantial agreement was observed among pathologists (κ = 0.6, p < 0.001). On multivariate analysis, Acc was associated with the number of previously interpreted cases, with a predicted Acc of 82% at the end of learning curve. The overall average accuracy for high Gleason score (>3 + 3) determination was of 72%, although results were limited by the small amount of cases. CONCLUSIONS: FFOCT of prostate biopsy cores may provide a diagnostic accuracy greater than 80%, with a good reliability and a high NPV. TAKE HOME MESSAGE: "Full-field optical coherence tomography is a novel imaging modality that could have a potential value in real-time diagnosis of prostate cancer during prostate biopsy procedures."

Detection of significant prostate cancer with magnetic resonance targeted biopsies--should transrectal ultrasound-magnetic resonance imaging fusion guided biopsies alone be a standard of care?

PURPOSE: Magnetic resonance imaging-transrectal ultrasound fusion targeted prostate biopsies were suggested to detect significant cancer with more accuracy than systematic biopsies. In this study we evaluate the pathological characteristics of multiparametric magnetic resonance imaging detected and undetected tumor foci on radical prostatectomy specimens. MATERIALS AND METHODS: We selected 125 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to the PI-RADS score. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or tumor volume greater than 0.5 ml were considered significant. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. RESULTS: Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Of these, 137 were considered significant (Gleason score greater than 3+3 in 112) and were observed in 111 (89%) glands. A total of 95 individual tumor foci, including 14 significant foci, were missed with multiparametric magnetic resonance imaging. All of them were located in glands where another focus was detected with multiparametric magnetic resonance imaging. An additional 9 individual tumor foci, including 7 significant, were detected on multiparametric magnetic resonance imaging but missed with targeted biopsy, resulting in 5 (4%) significant cancers undetected with magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy. The magnetic resonance imaging target largest diameter was associated with high volume (greater than 0.5 cc) foci detection, while PI-RADS score and cancer involvement on targeted biopsy were associated with significant foci detection. CONCLUSIONS: In these series of men with suspicious prostate multiparametric magnetic resonance imaging findings, magnetic resonance imaging-transrectal ultrasound fusion guided targeted biopsy alone strategy would have resulted in the under detection of only 4% significant cancers.

CXCR4 is highly expressed at the tumor front but not in the center of prostate cancers.

OBJECTIVE: To evaluate the expression of CXCR4, its ligand SDF-1, ß-catenin and E-cadherin throughout the local tumor microenvironment of prostate cancer. PATIENTS AND METHODS: A total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and distant peritumoral tissue (D). Immunohistochemical analysis was used to investigate the expression patterns of CXCR4, E-cadherin and ß-catenin. Clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules' expression was statistically assessed. RESULTS: CXCR4 mRNA and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level gradually increased from the tumor center to the distant peritumoral tissue. High CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the tumor front was associated with locally advanced cancer and disease recurrence. Moreover, high CXCR4 staining at the tumor front and increased cytosolic E-cadherin expression in the same location was associated with locally advanced disease. CONCLUSIONS: CXCR4 seems overexpressed at the tumor front of prostate tumors, where it potentially promotes cell migration toward the SDF-1 centrifugal attracting gradient, as well as epithelial-mesenchymal transition. High CXCR4 and low SDF-1 levels at tumor front were both associated with adverse histological features.

Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation?

PURPOSE: We determined whether endorectal multiparametric magnetic resonance imaging at 1.5 Tesla could predict tumor target volume in the perspective of focal therapy of prostate cancer. MATERIALS AND METHODS: A total of 84 consecutive patients underwent multiparametric magnetic resonance imaging before radical prostatectomy. The volume of each suspicious area detected on magnetic resonance imaging and of all surgical histological foci was determined by planimetry. We first used each magnetic resonance imaging sequence (T2-weighted, diffusion weighted and dynamic contrast enhanced) and then the sequence showing the largest tumor area (multiparametric volume). Finally, the largest area of any sequence was used to calculate a target volume according to the volume of a cylinder. Agreement between magnetic resonance imaging and pathological findings was assessed by linear regression and residual analysis. RESULTS: Histology revealed 99 significant tumors with a volume of greater than 0.2 cc and/or a Gleason score of greater than 6. Of the tumors 16 (16.2%) were undetected by multiparametric magnetic resonance imaging. Linear regression analysis showed that tumor volume estimated by T2-weighted or diffusion weighted imaging correlated significantly with pathological volume (r(2) = 0.82 and 0.83, respectively). Residuals from diffusion weighted imaging volume estimations did not significantly differ from 0. Nevertheless, diffusion weighted imaging underestimated pathological volume in 43 of 87 cases (49%) by a mean of 0.56 cc (range 0.005 to 2.84). Multiparametric and target volumes significantly overestimated pathological volume by a mean of 16% and 44% with underestimation in 28 (32%) and 15 cases (17%), respectively. Volume underestimation was significantly higher for tumor foci less than 0.5 cc. The percent of Gleason grade 4 did not influence tumor volume estimation. CONCLUSIONS: Magnetic resonance imaging can detect most significant tumors. However, delineating a target volume may require further adjustment before planning magnetic resonance imaging targeted focal treatment.

Prebiopsy magnetic resonance imaging and prostate cancer detection: comparison of random and targeted biopsies.

PURPOSE: We compared the accuracy of visual targeted biopsies vs computerized transrectal ultrasound-magnetic resonance imaging registration using a rigid (Esaote®, nondeformable) or elastic (Koelis®, deformable) approach. MATERIALS AND METHODS: A total of 391 consecutive patients with suspected localized prostate cancer were prospectively included in analysis. All patients underwent prostate magnetic resonance imaging, followed by 10 to 12-core random prostate biopsies. When magnetic resonance imaging detected suspicious findings, targeted biopsy was performed, including visual, rigid system and elastic system targeted biopsies in the first 127 patients, the next 131 and the last 133, respectively. Cancer detection rates were assessed by conditional logistic regression. Targeted biopsies alone and random biopsies were further compared for the amount of tissue sampled and microfocal cancer detection, the latter defined as a single core with 5 mm or less of Gleason 6 cancer. RESULTS: Patient characteristics and random biopsy detection rates were similar among the groups. Magnetic resonance imaging detected at least 1 suspicious area in 54 (42%), 78 (59%) and 82 patients (62%) in groups 1, 2 and 3, respectively. The cancer detection rates of rigid and elastic system targeted biopsies were significantly higher than the random biopsy rate (p = 0.0065 and 0.0016, respectively). Visual targeted biopsy did not perform better than random biopsy (p = 0.66). Rigid and elastic system targeted biopsies allowed for decreasing the number of cores and the detection of microfocal cancer, while increasing the detection of high grade cancer. CONCLUSIONS: When performed with computerized magnetic resonance imaging-transrectal ultrasound image registration, targeted biopsy alone improved cancer detection over random biopsies, decreased the detection rate of microfocal cancer and increased the detection rate of cancer with a Gleason score of greater than 6.

Non eosinophilic chronic stricturing esophagitis: Lessons from thirty eight cases.

BACKGROUND AND AIMS: The endoscopic workup of dysphagia can lead to the diagnosis of atypical esophagitis, with thickened esophageal mucosa, strictures, mucosal exudates, furrows, and sloughing. While these aspects suggest eosinophilic esophagitis, pathology might not report the presence of eosinophils, but rather chronic inflammation, with spongiosis, parakeratosis, and lymphocytic infiltrate. We aimed to report the management of this disease and assess the prevalence of associated dermatological conditions. METHODS: We retrospectively evaluated the medical records of our patients with non-eosinophilic stricturing esophagitis for clinical, endoscopy, and pathology data. Patients were evaluated by a dermatologist. A blood immunoassay and skin biopsy were performed if needed. RESULTS: Thirty-eight patients (twenty-six women) were included in the study. The median age at onset of symptoms was 56.5 years, with a median duration of symptoms of two years. Thirty-five patients presented with dysphagia at diagnosis and eighteen with weight loss. At endoscopy, a single esophageal stenosis was diagnosed in 19 patients, localized in the upper third in 22 patients. Thirty patients received endoscopic treatment (dilatation in 29/38 and local triamcinolone injection in 11/38 patients). In 21 patients, oral, skin or vulvo-anal lesions were found on dermatological examination. Nineteen patients received systemic treatment, including corticosteroids, immunosuppressive drugs and plasmapheresis. Five patients developed esophageal squamous cell carcinoma. CONCLUSION: The management of non-eosinophilic chronic stricturing esophagitis is challenging, because of a low contribution of esophageal biopsies and the refractory nature of the strictures. In our experience, a dermatological evaluation helped in 55% of cases to introduce a systemic treatment, leading to limit the use of endoscopic dilatation. Endoscopic follow-up is needed, considering the significant risk of esophageal squamous cell carcinoma.

Endoscopic submucosal dissection versus endoscopic mucosal resection for early esophageal adenocarcinoma.

OBJECTIVES: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow endoscopic resection of early esophageal adenocarcinoma. The choice between the two techniques takes into account the morphology of the lesion, and the experience of the endoscopist. The aim of this study was to compare EMR to ESD for the treatment of early esophageal adenocarcinoma. METHODS: Patients who underwent an endoscopic resection for esophageal adenocarcinomas between March 2015 and December 2019 were included. ESD was compared to EMR in terms of clinical, procedural, histologic, and oncologic outcomes. RESULTS: 85 patients were included: 57 ESD and 28 EMR. The median (IQR) diameter of the lesion was 20(15-25) mm in the ESD group, and 15(8-16) mm in the EMR group, p<0.01. ESD allowed en bloc resection in 100% of cases, and EMR in 39% of cases, p<0.001. The R0 and curative resection rate in the ESD group versus the EMR group were 88% and 67%, respectively, versus 21% and 11%, p<0.001. We recorded one severe adverse event, in the EMR group. After a median (IQR) follow-up of 27.5 (14.5-38.7) months, the local recurrence rate was 23% vs. 18% (p = 0.63), and the overall survival 89% vs. 86% (p = 0.72), in the ESD and EMR groups, respectively. CONCLUSION: ESD was as safe as EMR and allowed higher en bloc, R0 and curative resection rates. Although these results did not translate into long-term outcomes, these data prompt for a broader adoption of ESD for the resection of esophageal lesions suspected of harboring early esophageal adenocarcinoma.

Mechanisms of esophageal stricture after extensive endoscopic resection: a transcriptomic analysis.

Background and study aims Esophageal stricture is the most frequent adverse event after endoscopic resection for early esophageal neoplasia. Currently available treatments for the prevention of esophageal stricture are poorly effective and associated with major adverse events. Our aim was to identify transcripts specifically overexpressed or repressed in patients who have developed a post-endoscopic esophageal stricture, as potential targets for stricture prevention. Patients and methods We conducted a prospective single-center study in a tertiary endoscopy center. Patients scheduled for an endoscopic resection and considered at risk of esophageal stricture were offered inclusion in the study. The healthy mucosa and resection bed were biopsied on Days 0, 14, and 90. A transcriptomic analysis by microarray was performed, and the differences in transcriptomic profile compared between patients with and without esophageal strictures. Results Eight patients, four with esophageal stricture and four without, were analyzed. The mean ± SD circumferential extension of the mucosal defect was 85 ±â€Š11 %. The transcriptomic analysis in the resection bed at day 14 found an activation of the interleukin (IL)-1 group (Z score = 2.159, P  = 0.0137), while interferon-gamma (INFγ) and NUPR1 were inhibited (Z score = -2.375, P  = 0.0022 and Z score = -2.333, P  = 0.00131) in the stricture group. None of the activated or inhibited transcripts were still significantly so in any of the groups on Day 90. Conclusions Our data suggest that IL-1 inhibition or INFγ supplementation could constitute promising targets for post-endoscopic esophageal stricture prevention.

Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies.

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting.

Endoscopic submucosal dissection for early esophagogastric junction adenocarcinomas: a systematic review.

Background: Esophagogastric junction adenocarcinomas (EGJAs) include esophageal and gastric cardia adenocarcinomas (GCAs). These tumors are currently regarded as a single entity, with similar surgical and oncological therapies, although they originate from different organs. Endoscopy allows an early-stage diagnosis, where both subtypes can be differentiated. With this review we aimed to describe the outcomes of endoscopic submucosal dissection for the treatment of esophageal adenocarcinomas (EAs) and GCAs. Methods: We identified studies by screening PubMed, Embase and Web of Science. We included all 19 studies that mentioned at least one of the following criteria of interest: en bloc; R0 resection; local recurrences; and/or overall survival. Results: We found an en bloc resection rate superior to 90% for both tumors. R0 resections rates were over 60% for most EAs, vs. 83% for most GCAs. We recorded less than 13% and 20% early and late adverse events for EA, and 10% and 7% for GCA. The local recurrence rate was 8% for EA and 3% for GCA. The overall survival was over 90%. Conclusions: Endoscopic submucosal dissection is safe and effective for esophageal and GCAs. These data support the extension of the use of endoscopic submucosal dissection to all EGJAs, including early EAs.

Endoscopic ultrasound guided fine needle biopsy in patients with suspected gastric linitis plastica.

BACKGROUND: Gastric linitis plastica (GLP) is a diffuse infiltrating type of gastric adenocarcinoma. It is associated with a poor prognosis and a five-year survival of 3-10%. The infiltrating profile of this tumor explains the low yield of the superficial mucosal biospies. The objective of this study was to investigate the role of endoscopic ultrasound-fine needle biopsy (EUS-FNB) in the diagnosis of GLP. METHODS: We performed a retrospective analysis including all patients who had an EUS-FNB, at a tertiary referral center, over the last 3 years. The primary outcome was the sensitivity of EUS-FNB in patients with suspected GLP. RESULTS: Between January 2017 and December 2020, 34 patients had an EUS-FNB for suspected GLP. Ten patients had a diagnostic of GLP. This diagnosis was obtained by EUS-FNB in 90% (9/10) of the cases. Eight patients had at least one previous esophagogastroduodenoscopy (EGD) with negative mucosal biopsies. Gastric EUS-FNB helped diagnose other serious conditions in 47% (16/34) of cases with inconclusive mucosal biopsies. CONCLUSION: Gastric EUS-FNB in patients with suspected GLP and normal endoscopic mucosal biopsies may lead to a positive diagnosis of GLP in 90% of cases without notable adverse events. This technique should be considered as a second step in the setting of suspicion of GLP after inconclusive mucosal biopsies.