Sujet(s)
Pneumopéritoine , Emphysème sous-cutané , Humains , Cholangiopancréatographie rétrograde endoscopique/effets indésirables , Pneumopéritoine/imagerie diagnostique , Pneumopéritoine/étiologie , Emphysème sous-cutané/imagerie diagnostique , Emphysème sous-cutané/étiologie , Duodénum , Membre inférieurRÉSUMÉ
Deficient mismatch repair (MMR) proteins may lead to DNA damage and microsatellite instability. Primary sclerosing cholangitis (PSC) is a risk factor for colitis-associated colon cancer. MiR-155 is suggested to act as a key regulating node, linking inflammation and tumorigenesis. However, its involvement in the chronic colitis of PSC-UC patients has not been examined. We investigated the involvement of miR-155 in the dysregulation of MMR genes and colitis in PSC patients. Colon tissue biopsies were obtained from patients with PSC, PSC with concomitant ulcerative colitis (PSC-UC), uncomplicated UC, and healthy controls (n = 10 per group). In the ascending colon of PSC and PSC-UC patients, upregulated miR-155 promoted high microsatellite instability and induced signal transducer and activator of transcription 3 (STAT-3) expression via the inhibition of suppressors of cytokine signalling 1 (SOCS1). In contrast, the absence of miR-155 overexpression in the sigmoid colon of PSC-UC patients activated the Il-6/S1PR1 signalling pathway and imbalanced the IL17/FOXP3 ratio, which reinforces chronic colitis. Functional studies on human intestinal epithelial cells (HT-29 and NCM460D) confirmed the role of miR-155 over-expression in the inhibition of MMR genes and the modulation of p53. Moreover, those cells produced more TNFα upon a lipopolysaccharide challenge, which led to the suppression of miR-155. Additionally, exposure to bile acids induced upregulation of miR-155 in Caco-2 cell lines. Thus, under different conditions, miR-155 is involved in either neoplastic transformation in the ascending colon or chronic colitis in the sigmoid colon of patients with PSC. New insight into local modulation of microRNAs, that may alter the course of the disease, could be used for further research on potential therapeutic applications.
Sujet(s)
Angiocholite sclérosante , Rectocolite hémorragique , Réparation de mésappariement de l'ADN , microARN , Cellules Caco-2 , Transformation cellulaire néoplasique , Angiocholite sclérosante/complications , Angiocholite sclérosante/génétique , Angiocholite sclérosante/métabolisme , Rectocolite hémorragique/métabolisme , Côlon/métabolisme , Réparation de mésappariement de l'ADN/génétique , Humains , microARN/génétique , microARN/métabolisme , Instabilité des microsatellites , Protéine-1 suppressive de la signalisation des cytokines/génétique , Protéine-1 suppressive de la signalisation des cytokines/métabolisme , Protéines SOCS/génétique , Protéines SOCS/métabolisme , Protéine p53 suppresseur de tumeur/génétique , Protéine p53 suppresseur de tumeur/métabolismeRÉSUMÉ
INTRODUCTION: Rectal neuroendocrine neoplasms (rNENs) are potentially metastatic lesions. False endoscopic diagnosis and subsequent treatment may lead to nonradical resection and metastases. OBJECTIVES: This study aimed to analyze the clinical characteristics of rNENs, investigate whether the lesion origin was suspected by endoscopists during examination and if those lesions were subsequently removed using the appropriate method, and assess the outcomes of patients after curative and noncurative resections. PATIENTS AND METHODS: We analyzed the records of patients hospitalized in our department (2006-2019) with a diagnosis of rNENs. We included 40 patients with rNENs, evaluated their clinical characteristics, and investigated whether the neuroendocrine origin of the lesions was suspected on endoscopy. We compared the outcomes of patients treated with the proper method (endoscopic submucosal dissection / endoscopic mucosal resection [ESD / EMR]) and those treated with polypectomy. RESULTS: Abnormalities appeared as typical, yellowish subepithelial lesions (n = 24), lesions resembling hyperplastic polyps (n = 12), or tumors with central depression (n = 4). The median size was 5.5 mm and most of them were G1 lesions (n = 36). Only 14 of them were suspected to be of neuroendocrine origin at the first endoscopic examination, and 12 were removed by ESD / EMR. The remaining tumors (n = 26) were removed using polypectomy. Most of the patients were diseasefree at followup, but 2 patients after polypectomy and a single patient after nonradical ESD developed metastases. CONCLUSION: In most cases, the origin of the lesion was not suspected on colonoscopy and subsequently the tumor was removed using an inappropriate method. Endoscopists do not follow the guidelines when dealing with patients with rNENs and more emphasis should be placed on education on the management of rNENs.
Sujet(s)
Tumeurs neuroendocrines , Tumeurs du rectum , Humains , Muqueuse intestinale , Tumeurs neuroendocrines/chirurgie , Tumeurs du rectum/chirurgie , Études rétrospectives , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging technique in the treatment of Zenker's diverticulum (ZD). This study aimed to analyze the feasibility of Zenker's POEM (Z-POEM) in a multicenter setting and assess its performance using a validated Kothari-Haber Scoring System newly developed for symptom measurement in ZD. MATERIALS AND METHODS: This was a multicenter retrospective study involving three Polish tertiary referral endoscopic units. The data of consecutive patients with symptomatic ZD treated with Z-POEM in Poland between May 2019 and August 2020 were retrieved and analyzed. Primary outcome measures were technical success and clinical success rate (<3 points in Kothari-Haber Score at 2-3 months follow-up). Secondary outcome measures included procedures' duration, length of hospital stay, and adverse events. RESULTS: 22 patients with symptomatic ZD were included. The mean age was 67.6 (±10.7) years, and 14 (63.6%) were male. All but two patients were treatment naïve. The average size of the ZD was 30 mm (IQR, 24-40 mm). Technical success was achieved in all patients (100%), whereas clinical success was 90.9%. The average Kothari-Haber Score was 6.35 before treatment and has dropped to 0.65 after the treatment (p < 0.0001). The mean procedure time was 48.8 (±19.3) minutes, and the median length of hospital stay was 2 days (IQR, 2-3). Three patients (13.6%) had post-procedural emphysema, of which two were mild and self-resolving (9.1%), and one was moderate (4.5%) and complicated with laryngeal edema and prolonged intubation. CONCLUSIONS: This feasibility study suggests that Z-POEM is a highly effective and safe treatment for ZD, particularly among treatment-naïve patients. Comparative studies with other treatment modalities over longer follow-up are warranted.
RÉSUMÉ
Objectives: Gastric cancer (GC) in young patients is a troubling clinical problem. The aim of this study was to analyze whether patients ≤40 years of age with GC differ from patients (age >40 years) in terms of clinicopathological and selected genetic factors.Materials and methods: Between 1984 and 2011, data were collected for 840 GC patients diagnosed and treated for GC at the Department of Gastroenterology at Pomeranian Medical University. The following clinicopathological features were compared between two age groups: sex, symptom duration, family history of cancer, tumor site, stage (early vs. advanced), blood group, histology, Helicobacter pylori infection and BRCA2 C572T silent mutation status.Results: A total of 65 (7.7%) patients were age 40 years or younger. GC was predominant in women in the younger group (p < .001). Patients (≤40 years) more frequently reported a positive family history of cancer (p = .01) and a diffuse tumor type was more common in this group (p < .001). The two age groups did not differ significantly regarding symptom duration, tumor location or stage, H. pylori infection, blood group, or BRCA2 C572T silent mutation status. A comparison of male and female patients aged 40 years or less did not reveal sex-based differences in any analyzed features.Conclusion: Patients ≤40 years of age with GC differ from patient >40 years of age in having a predominance of women, diffuse tumor type, and positive family history of cancer. These results offer openings for further investigation of the relevance of these differences.
Sujet(s)
Infections à Helicobacter/complications , Tumeurs de l'estomac/diagnostic , Système ABO de groupes sanguins , Adolescent , Adulte , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Protéine BRCA2/génétique , Femelle , Infections à Helicobacter/diagnostic , Infections à Helicobacter/épidémiologie , Helicobacter pylori , Humains , Mâle , Adulte d'âge moyen , Mutation , Stadification tumorale , Pologne , Études rétrospectives , Facteurs de risque , Tumeurs de l'estomac/épidémiologie , Tumeurs de l'estomac/génétique , Jeune adulteRÉSUMÉ
BACKGROUND AND AIMS: The diagnosis of gastric premalignant conditions (GPCs) relies on endoscopy with mucosal sampling. We hypothesized that the endoscopist biopsy rate (EBR) might constitute a quality indicator for EGD, and we have analyzed its association with GPC detection and the rate of missed gastric cancers (GCs). METHODS: We analyzed EGD databases from 2 high-volume outpatient units. EBR values, defined as the proportion of EGDs with ≥1 biopsy to all examinations were calculated for each endoscopist in Unit A (derivation cohort) and divided by the quartile values into 4 groups. Detection of GPC was calculated for each group and compared using multivariate clustered logistic regression models. Unit B database was used for validation. All patients were followed in the Cancer Registry for missed GCs diagnosed between 1 month and 3 years after EGDs with negative results. RESULTS: Sixteen endoscopists in Unit A performed 17,490 EGDs of which 15,340 (87.7%) were analyzed. EBR quartile values were 22.4% to 36.7% (low EBR), 36.8% to 43.7% (moderate), 43.8% to 51.6% (high), and 51.7% and 65.8% (very-high); median value 43.8%. The odds ratios for the moderate, high, and very-high EBR groups of detecting GPC were 1.6 (95% confidence interval [CI], 1.3-1.9), 2.0 (95% CI, 1.7-2.4), and 2.5 (95% CI, 2.1-2.9), respectively, compared with the low EBR group (P < .001). This association was confirmed with the same thresholds in the validation cohort. Endoscopists with higher EBR (≥43.8%) had a lower risk of missed cancer compared with those in the lower EBR group (odds ratio, 0.44; 95% CI, 0.20-1.00; P = .049). CONCLUSIONS: The EBR parameter is highly variable among endoscopists and is associated with efficacy in GPC detection and the rate of missed GCs.
Sujet(s)
Biopsie/statistiques et données numériques , Gastrite atrophique/anatomopathologie , Gastroscopie/normes , États précancéreux/anatomopathologie , Indicateurs qualité santé , Tumeurs de l'estomac/anatomopathologie , Adénomes/diagnostic , Adénomes/anatomopathologie , Adolescent , Adulte , Sujet âgé , Soins ambulatoires , Oesophage de Barrett/diagnostic , Oesophage de Barrett/anatomopathologie , Études de cohortes , Tumeurs du duodénum/diagnostic , Tumeurs du duodénum/anatomopathologie , Femelle , Gastrite atrophique/diagnostic , Humains , Mémorisation et recherche des informations , Modèles logistiques , Mâle , Métaplasie , Adulte d'âge moyen , Analyse multifactorielle , Pologne , États précancéreux/diagnostic , Études rétrospectives , Lésions malpighiennes intra-épithéliales/diagnostic , Lésions malpighiennes intra-épithéliales/anatomopathologie , Estomac/anatomopathologie , Tumeurs de l'estomac/diagnostic , Jeune adulteRÉSUMÉ
Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower KM values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool.
Sujet(s)
Acides et sels biliaires/métabolisme , Cholestase/urine , Glucuronides/urine , Glucuronosyltransferase/métabolisme , ARN messager/métabolisme , Sujet âgé , Cholestase/sang , Cholestase/thérapie , Femelle , Glucuronides/sang , Glucuronosyltransferase/génétique , Humains , Rein/enzymologie , Mâle , Microsomes du foie/enzymologie , Adulte d'âge moyen , EndoprothèsesRÉSUMÉ
INTRODUCTION: EUS-guided ethanol ablation of insulinoma is a new method of treatment of this neuroendocrine tumour. Ablation is recommended in patients who are poor surgical candidates or refuse surgery. We present a case of an 81-year-old female with symptomatic insulinoma, treated successfully with EUS-guided alcoholic ablation, along with a literature review including 28 other previously described cases. The effectiveness, safety of the therapy, and technical procedure-related issues are summarised. To the best of our knowledge, this is the first described case of successful insulinoma EUS-guided ablation in Poland. MATERIAL AND METHODS: We searched the PubMed/Medline database to identify cases of EUS-guided alcoholic ablation. Our analysis included 14 articles (case reports or case series), with a total of 27 patients and 31 tumours described, published before February 2017. RESULTS: The described tumours were relatively small (mean 13 mm), and the most common location was pancreatic head. The mean ethanol volume injected to the tumour was 1.8 ml and the concentration of infused alcohol varied from 95% to 98%.Side effects were observed in six cases; apart from one, they were mild and self-limiting. There was only one severe adverse event, treated conservatively with success. The median follow-up was 14.4 months (2-55 months). In all described cases ablation led to improvement of the symptoms and normalisation of glycaemia. CONCLUSIONS: The EUS-guided alcoholic ablation of insulinoma is a safe and effective method of treatment in patients who are poor surgical candidates and/or refuse surgery. The adverse effects are rare and mild and were observed when the volume of injected ethanol was equal to or above 3.0 ml. However, the data is limited, the follow-up is relatively short, and prospective studies are needed to confirm the long-term effects of treatment. The study shows also that there are important procedural differences (concentration and volume of alcohol, needle gauge, number of sessions) between the endoscopists, which should be specified.
Sujet(s)
Techniques d'ablation , Éthanol , Insulinome/chirurgie , Tumeurs du pancréas/chirurgie , Sujet âgé de 80 ans ou plus , Femelle , Études de suivi , Humains , Pologne , Résultat thérapeutiqueRÉSUMÉ
The aim of this study was to assess the: 1) clinicopathologic features of papillary early gastric cancer (PEGC) (13 cases) compared to tubular early gastric cancer (TEGC) (41 cases); 2) efficiency of endoscopic submucosal dissection (ESD) in treatment of PEGC. From January 2007 to February 2016, a total of 54 consecutive patients with early gastric cancer (EGC) underwent ESD at the Department of Gastroenterology of the Pomeranian Medical University in Poland. The histologic type of carcinoma was assessed according to the WHO histological classification of GC. The extension of GC into the submucosa was measured using the Aperio Scan Scope image analysis system tools. PEGCs were diagnosed in 24.1% of the cases of EGC. PEGCs were significantly more elevated in macroscopic examination and better demarcated tumors than TEGC. There were no significant differences between gender, tumor location, ulceration, tumor size, depth of invasion (T), presence of intestinal metaplasia and lymphocytic infiltrate. Curative resection was achieved in 87.1% of patients with EGCs treated with ESD. The lower rate of curative resection (R0) observed in PEGC (76.9%) vs TEGC (90.2%) was not statistically significant. Further studies will be necessary to confirm the clinical and morphological presentation of PEGCs.
Sujet(s)
Adénocarcinome/anatomopathologie , Tumeurs de l'estomac/anatomopathologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Mucosectomie endoscopique , Femelle , Humains , Mâle , Adulte d'âge moyenRÉSUMÉ
Mediastinal pseudocysts are a rare complication of acute pancreatitis. Lack of uniform treatment standards makes the management of this condition a clinical challenge. We report the case of a 43-year-old patient who presented with a left pleural effusion. Pleural fluid revealed a high amylase concentration consistent with a pancreaticopleural fistula. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a disruption of the pancreatic duct with free outflow of contrast medium into the thoracic cavity. A pancreatic stent was placed. The second day after the ERCP, the patient developed septic shock and was admitted to the intensive care unit. Computed tomography (CT) revealed mediastinal pseudocysts and bilateral pleural effusions. After bilateral drainage of the pleural cavities, the patient improved clinically, and a follow-up CT scan showed that the fluid collection and pseudocysts had resolved. We discuss the optimal strategies for diagnosing and treating patients with pancreatic thoracic pseudocysts and fistulas, as well as review the management of these conditions.
RÉSUMÉ
OBJECTIVE: Early gastric cancer (EGC) is defined as cancer invasion confined to the mucosa or submucosa, irrespective of lymph node metastasis. Recently endoscopic submucosal dissection (ESD) has been widely accepted for the treatment for dysplasia and EGC without lymph node metastases. While the method has been advanced in Far East countries, ESD is still being developed in Europe and has not gained enough popularity although it has been recommended as the treatment of choice for superficial gastric neoplastic lesions by European Society of Gastrointestinal Endoscopy (ESGE) in 2015. METHODS: The aim of the study was to perform a retrospective analysis of clinical and histomorphologic features of 58 cases of EGCs removed by ESD in a university hospital in Western Pomerania in Poland and to evaluate factors related to the efficiency of ESD resection. RESULTS: With univariate analysis, indications for ESD with the highest R0 rate were found in EGCs limited to mucosa (T1a, small mucosal, M), without muscularis mucosa invasion, localised in the middle/lower part of stomach and intestinal type in histological examination. The R0 complete resection rate was significantly (p < 0.0001) lower for T1b than that for T1a tumours (21.4% vs. 100%). Tumours with submucosal involvement were associated with lower efficiency of ESD procedure. CONCLUSIONS: Our data showed that in EGCs with favourable histomorphologic characteristics, ESD seemed to be a totally efficient and safe method of treatment in a European small-volume centre. R0 resection rate reached 81.1% of cases and median time of the ESD procedure was 61.5 min.
Sujet(s)
Adénocarcinome/anatomopathologie , Adénocarcinome/chirurgie , Mucosectomie endoscopique/méthodes , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/chirurgie , Sujet âgé , Sujet âgé de 80 ans ou plus , Dissection/méthodes , Mucosectomie endoscopique/effets indésirables , Femelle , Muqueuse gastrique/anatomopathologie , Humains , Métastase lymphatique/anatomopathologie , Adulte d'âge moyen , Pologne , Études rétrospectivesRÉSUMÉ
Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblastlike stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma. We wondered if a similar correlation occurs in patients with colorectal cancer (CRC). A total of 46 patients were enrolled in this study: 17 with CRC, 18 with benign colonic adenomas (BCA) and 11 healthy individuals. By employing fluorescence-activated cell sorting (FACS) we evaluated the number of BM-derived SCs circulating in PB: i) CD34+/Lin-/CD45- and CD133-/Lin-/CD45- VSELs; ii) CD45-/CD105+/CD90+/CD29+ MSCs; iii) CD45-/CD34+/CD133+/KDR+ endothelial progenitor cells (EPCs); and iv) CD133+/Lin-/CD45+ or CD34+/Lin-/CD45+ cells enriched for hematopoietic stem/progenitor cells (HSPCs). In parallel, we measured in the PB parameters regulating the egress of SCs from BM into PB. In contrast to pancreatic and gastric cancer patients, CRC subjects presented neither an increase in the number of circulating SCs nor the activation of pro-mobilizing factors such as complement, coagulation and fibrinolytic cascade, circulating stromal derived factor 1 (SDF1), vascular endothelial growth factor (VEGF) and intestinal permeability marker (zonulin). In conclusion, mobilization of SCs in cancer patients depends on the type of malignancy and its ability to activate pro-mobilization cascades.
Sujet(s)
Adénomes/sang , Tumeurs colorectales/sang , Cellules souches/métabolisme , Adénomes/anatomopathologie , Adulte , Sujet âgé , Études cas-témoins , Tumeurs colorectales/anatomopathologie , Femelle , Facteur de croissance des hépatocytes/sang , Humains , Mâle , Adulte d'âge moyen , Facteur de croissance endothéliale vasculaire de type A/sangRÉSUMÉ
BACKGROUND Mutations in DNA of mismatch repair (MMR) genes result in failure to repair errors that occur during DNA replication in microsatellites, resulting in accumulation of frameshift mutations in these genes and leading to DNA mismatch replication errors and microsatellite instability. Gastric cancers (GCs) with high MSI (MSI-H) are a well-defined subset of carcinomas showing distinctive clinicopathological features. In this study we investigated the rate of MSI and the correlation between MSI status and clinicopathological features of GC. MATERIAL AND METHODS The study included 107 patients with GCs: 61 with advanced gastric cancers (AGC) and 46 with early gastric cancer (EGC). MSI deficiency in GCs was assessed by the immunohistochemical analysis of expression of MMR proteins - MLH1, MSH2, MSH6, and PMS2 - using formalin-fixed and paraffin-embedded tissue. RESULTS A total of 6 (5.6%) MSI-H were observed. The loss of MMR proteins expression was associated with the intestinal type of GC in Lauren classification, and tubular and papillary architecture in WHO classification. There was no statistically significant association between negative MMR expression and other selected clinical parameters: age, sex, tumor location, depth of invasion (EGC and AGC), lymph nodes status, presence of the ulceration, and lymphocytic infiltrate. CONCLUSIONS In the present era of personalized medicine, the histological type of GC and MMR proteins status in cancer cells are very important for the proper surveillance of patients with familial GC and sporadic GCs, as well as for selecting the proper follow-up and treatment. Larger collaborative studies are needed to verify the features of MSI-H GCs in Poland.
Sujet(s)
Réparation de mésappariement de l'ADN , Instabilité des microsatellites , Tumeurs de l'estomac/génétique , Sujet âgé , Protéines de liaison à l'ADN/génétique , Protéines de liaison à l'ADN/métabolisme , Femelle , Régulation de l'expression des gènes tumoraux , Humains , Immunohistochimie , Mâle , Adulte d'âge moyen , Mismatch repair endonuclease PMS2/génétique , Mismatch repair endonuclease PMS2/métabolisme , Protéine-1 homologue de MutL/génétique , Protéine-1 homologue de MutL/métabolisme , Protéine-2 homologue de MutS/génétique , Protéine-2 homologue de MutS/métabolisme , Pologne , Tumeurs de l'estomac/métabolisme , Transcriptome/génétiqueRÉSUMÉ
BACKGROUND: Gastric cancer (GC) is part of the spectrum of diseases linked to BRCA1 and BRCA2 mutations that increase the risk of breast and ovarian cancer. Data suggesting an increased risk of developing GC among BRCA1 and BRCA2 mutation carriers are based almost exclusively on indirect studies. The objective was to assess in a direct study whether there is a relationship between GC and selected recurrent BRCA1 and BRCA2 mutations in the Polish population. METHODS: Three hundred seventeen GC patients (193 males and 124 females; mean age 59.5 ± 12.8 y) diagnosed at the Department of Gastroenterology at the Pomeranian Medical University were included in this retrospective study. All patients were genotyped for 3 BRCA1 Polish founder mutations (5382insC, C61G and 4153delA) as well as for 9 known recurrent mutations in BRCA1 and BRCA2 genes. Genotyping was performed using allele-specific oligonucleotide polymerase chain reaction (ASA-PCR) for 4153delA and 5382insC, restriction fragment length polymorphism (PCR-RFLP) for C61G and TaqMan real-time PCR for 185delAG, 3819del5, 3875del4, 5370C > T, 886delGT, 4075delGT, 5467insT, 6174delT and 8138del5. RESULTS: Among tested mutations one founder BRCA1 mutation 5382insC was detected in two of 317 (0.63 %) GC cases. A comparison of frequency of detected BRCA1 founder mutations in GC patients to previously described 4570 Polish controls (0.63 % vs. 0.48 %) failed to indicate an increased risk of GC in the mutation carriers (OR = 1.3; 95 % CI 0.3-5.6, p = 0.71). A comparison of frequency of GC male cases and male controls (1.0 % vs. 0.43 %,OR = 1.5; 95 % CI 0.3-6.4, p = 0.61) allowed to formulate the same conclusion that there is no increased risk for GC for males. None of the 9 recurrent BRCA1 and BRCA2 mutations has been detected in tested GC patients. CONCLUSION: The current study indicates that founder BRCA1 mutations reported in Polish breast/ovarian cancer patients do not contribute to increased GC risk. The nine tested recurrent BRCA1 and BRCA2 mutations were not detected in GC patients which may suggests that they are rare in GC patients in the Polish population. Further analyses, including sequencing of entire sequences of BRCA1 and BRCA2 genes, are necessary to ultimately determine the role of these two genes in GC in Poland.
RÉSUMÉ
UNLABELLED: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. MAIN RECOMMENDATIONS: 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10âmm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett's esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15âmm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10â-â15âmm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).
Sujet(s)
Oesophage de Barrett/chirurgie , Dissection/normes , Endoscopie gastrointestinale/normes , Tumeurs gastro-intestinales/chirurgie , Oesophage de Barrett/diagnostic , Europe , Muqueuse gastrique , Tumeurs gastro-intestinales/diagnostic , Humains , Sélection de patientsRÉSUMÉ
INTRODUCTION: Gastric cancer (GC) belongs to a group of cancers linked to BRCA2 gene mutations and observed in patients with a family history of breast and ovarian cancers. A common variant allele (C5972T) observed in the BRCA2 gene in the Polish population is associated with an increased risk of breast cancer. OBJECTIVES: The objective of the study was to assess a relationship between the BRCA2 C5972T variant and GC. PATIENTS AND METHODS: A total of 380 patients with GC (234 men and 146 women; mean age, 59.0 ±12.8 years) and 380 sex- and age-matched healthy individuals (234 men and 146 women; mean age, 59.0 ±12.9 years) were included in this retrospective study. Polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) was used to detect the BRCA2 C5972T variant. We compared the frequency of BRCA2 allele carriers among patients and controls. We also compared selected clinical and pathological features between allele carriers and noncarriers among patients with GC. RESULTS: The BRCA2 C5972T variant was observed in 28 patients with GC (7.4%) and in 18 controls (4.7%) (P = 0.17). The odds ratio [OR] for GC in allele carriers was 1.59 (95% confidence interval [CI], 0.87-2.94). A comparison of selected clinical and pathological features between carriers and noncarriers did not show any significant differences. The analysis of a family history showed a trend for an increased risk of breast or ovarian cancer in the families of patients with GC carrying the C5972T allele (OR, 2.51; 95% CI, 0.80-7.88, P = 0.11). CONCLUSIONS: Our study showed that the C5972T allele is a low-penetrant variant of the BRCA2 gene, which tended to increase the risk of GC. Further research is needed to fully elucidate the role of BRCA2 polymorphisms in GC.
Sujet(s)
Gène BRCA2 , Prédisposition génétique à une maladie , Tumeurs de l'estomac/génétique , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Allèles , Études cas-témoins , Femelle , Génotype , Humains , Mâle , Adulte d'âge moyen , Pologne/épidémiologie , Polymorphisme de nucléotide simple , Études rétrospectives , Appréciation des risques , Tumeurs de l'estomac/épidémiologie , Jeune adulteRÉSUMÉ
AIM: To determine the prevalence and characteristics of additional primary malignancies in gastric cancer (GC) patients. METHODS: GC patients (862 total; 570 men, 292 women; mean age 59.8 ± 12.8 years) diagnosed at the Department of Gastroenterology at Pomeranian Medical University over a period of 23 years were included in this retrospective analysis of a prospectively maintained database. Mean follow-up time was 31.3 ± 38.6 mo (range 1-241 mo). The following clinicopathological features of patients with synchronous tumors were compared to those with metachronous tumors: age, sex, symptom duration, family history of cancer, tumor site, stage (early vs advanced), histology, and blood group. GC patients with and without a second tumor were compared in terms of the same clinicopathological features. RESULTS: Of 862 GC patients, 58 (6.7%) developed a total of 62 multiple primary tumors, of which 39 (63%) were metachronous and 23 (37%) synchronous. Four (6.9%) of the 58 multiple GC patients developed two or more neoplasms. The predominant tumor type of the secondary neoplasms was colorectal (n = 17), followed by lung (n = 9), breast (n = 8), and prostate (n = 7). Age was the only clinicopathological feature that differed between GC patients with synchronous vs metachronous malignancies; GC patients with synchronous neoplasms were older than those with metachronous neoplasms (68.0 ± 10.3 years vs 59.9 ± 11.1 years, respectively, P = 0.008). Comparisons between patients with and without a second primary cancer revealed that the only statistically significant differences were in age and blood group. The mean age of the patients with multiple GC was higher than that of those without a second primary tumor (63.4 ± 11.4 years vs 59.5 ± 13.0 years, respectively, P = 0.026). GC patients with a second primary tumor were more commonly blood group O than those without (56.2% vs 31.6%, respectively, P = 0.002). CONCLUSION: GC patients may develop other primary cancers; appropriate preoperative and postoperative diagnostic modalities are thus required, particularly if patients are older and blood group O.
Sujet(s)
Tumeurs primitives multiples , Seconde tumeur primitive , Tumeurs de l'estomac/anatomopathologie , Système ABO de groupes sanguins , Facteurs âges , Sujet âgé , Bases de données factuelles , Femelle , Humains , Mâle , Adulte d'âge moyen , Stadification tumorale , Pologne/épidémiologie , Prévalence , Études rétrospectives , Facteurs de risque , Tumeurs de l'estomac/sang , Tumeurs de l'estomac/épidémiologie , Facteurs tempsRÉSUMÉ
OBJECTIVE: Endoscopic submucosal dissection (ESD) has a high curative resection rate for gastrointestinal mucosal lesions, but is not used widely in Europe because of a high complication rate and a long learning curve. This study analyzed the ESD learning curve at a single European treatment center. MATERIALS AND METHODS: ESD and hybrid-ESD (hESD) procedures were used to treat large colonic lesions that could not be resected in one piece by other endoscopic methods. Procedure duration and speed, and en-bloc, complete (R0) resection, and complication rates were analyzed. RESULTS: Fifty-three patients underwent ESD (37 pure ESD, 16 hESD), most with rectal lesions (n=34, 64.2%). The mean lesion diameter was 3.7 ± 1.1 cm2 (range 2.0-7.0 cm), the median procedure duration was 70.0 min [interquartile range (IQR) 31.0-113.0 min], and the median treatment speed was 0.086 cm2/min (IQR 0.055-0.152). En-bloc and R0 resection rates were 86.5% (32/37) and 81.1% (30/37), respectively. Procedure speed increased significantly after about 25 cases (P=0.0313). The median hESD procedure treatment speed was 0.159 cm/min (n=16, IQR 0.094-0.193), which was better than with classical ESD (P=0.04). The hESD en-bloc and R0 resection rates were comparable to those of classical ESD (P>0.05). The only complication was bleeding, 5.7% (3/53); no perforation occurred. Recurrence was detected during follow-up (median 30.0 months, IQR 12-48) in one patient (1.7%). CONCLUSION: ESD is useful and safe for resection of large colorectal polyps, and procedure speed increased considerably after 25 procedures. hESD was faster than ESD, with a high therapeutic resection rate.
Sujet(s)
Coloscopie/méthodes , Tumeurs colorectales/chirurgie , Adénocarcinome/anatomopathologie , Adénocarcinome/chirurgie , Adénomes/anatomopathologie , Adénomes/chirurgie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Coloscopie/effets indésirables , Coloscopie/enseignement et éducation , Tumeurs colorectales/anatomopathologie , Dissection/effets indésirables , Dissection/enseignement et éducation , Dissection/méthodes , Formation médicale continue comme sujet/méthodes , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Durée opératoire , Résultat thérapeutiqueRÉSUMÉ
Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G), glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.
Sujet(s)
Acides et sels biliaires/toxicité , Acides et sels biliaires/urine , Cholestase/métabolisme , Cholestase/urine , Foie/métabolisme , Apoptose/effets des médicaments et des substances chimiques , Chénodiol/toxicité , Chénodiol/urine , Acide désoxycholique/toxicité , Acide désoxycholique/urine , Femelle , Cellules HepG2 , Humains , Acide lithocholique/toxicité , Acide lithocholique/urine , MâleRÉSUMÉ
Anatomic variations of the right biliary system are one of the most common risk factors for sectoral bile duct injury (BDI) during cholecystectomy. Isolated right posterior BDI may in particular be a challenge for both diagnosis and management. Herein we describe two cases of isolated right posterior sectoral BDI that took place during laparoscopic cholecystectomy. Despite effective external biliary drainage from the liver hilum in both cases, there was a persistent biliary leak observed which was not visible on endoscopic retrograde cholangiogram. Careful evaluation of images from both endoscopic and magnetic resonance cholangiograms revealed the diagnosis of an isolated right posterior sectoral BDI. These were treated with a delayed bisegmental (segments 6 and 7) liver resection and a Roux-en-Y hepaticojejunostomy respectively with good outcomes at 24 and 4 mo of follow-up. This paper discusses strategies for prevention of such injuries along with the diagnostic and therapeutic challenges it offers.