•GUT microbiota alterations have a role in gastrointestinal carcinogenesis.•GUT microbiota modulates the activity and the toxicity of several chemotherapy agents.•The manipulation of GUT microbiota ...could improve the chemotherapy efficacy.•Toxicity from chemotherapy could be reduced through GUT microbiota manipulation.
Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.
Background Differential diagnosis of pancreatic solid masses with EUS-guided FNA (EUS-FNA) is still challenging in about 15% of cases. Mutation of the K- ras gene is present in over 75% of pancreatic ...adenocarcinomas (PADC). Objective To assess the accuracy of K- ras gene mutation analysis for diagnosing PADC. Design We systematically searched the electronic databases for relevant studies published. Data from selected studies underwent meta-analysis by use of a bivariate model providing a pooled value for sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve. Setting Meta-analysis of 8 prospective studies. Patients Total of 931 patients undergoing EUS-FNA for diagnosis of pancreatic solid masses. Intervention K- ras mutation analysis. Main Outcome Measurements Diagnostic accuracy of K- ras mutation analysis and of combined diagnostic strategy by using EUS-FNA and K- ras mutation analysis in the diagnosis of PADC. Results The pooled sensitivity of EUS-FNA for the differential diagnosis of PADC was 80.6%, and the specificity was 97%. Estimated sensitivity and specificity were 76.8% and 93.3% for K- ras gene analysis, respectively, and 88.7% and 92% for combined EUS-FNA plus K- ras mutation analysis. Overall, K- ras mutation testing applied to cases that were inconclusive by EUS-FNA reduced the false-negative rate by 55.6%, with a false-positive rate of 10.7%. Not repeating EUS-FNA in cases in which mutation testing of the K- ras gene is inconclusive would reduce the repeat-biopsy rate from 12.5% to 6.8%. Limitations Small number of studies and between-study heterogeneity. Conclusion K- ras mutation analysis can be useful in the diagnostic work-up of pancreatic masses, in particular when tissue obtained by EUS-FNA is insufficient, and the diagnosis inconclusive.
Background Endoscopic procedures may represent an alternative to esophagectomy for superficial neoplasms of the esophagus (T1m/T1sm), but they are considered curative only in case of no lymph node ...involvement. Endoscopic ultrasound (EUS) is the most accurate method to define both T and N staging of esophageal carcinoma. Aims of the study were to assess the staging accuracy of EUS in superficial lesions (T1m and T1sm) of patients who were candidates for esophagectomy or local endoscopic resection and to establish which variables (site of neoplasm, histologic type, macroscopic appearance) can affect the accuracy of EUS in distinguishing between T1m and T1sm lesions. Methods The study population consisted of 55 patients with superficial carcinoma of the esophagus who underwent EUS (October 2002 to January 2007). Endoscopic ultrasound features were compared with findings from surgical specimens or samples obtained at mucosectomy. Results There were 33 patients with adenocarcinoma (60%), which developed on Barrett’s esophagus in 27 cases, 21 patients (38%) with squamous cell carcinoma, and 1 (2%) with lymphoepithelial-like carcinoma. All lesions were confirmed as T1 on pathology. Of the 22 (40%) T1m lesions on EUS, 19 (86%) were confirmed as T1m on pathology; of the 33 T1sm on EUS, 22 (66%) were confirmed as T1sm. Positive predictive value of EUS for invasion of the submucosa was 67%, negative predictive value 86%, sensitivity 88%, specificity 63%, and diagnostic accuracy 75%. The accuracy of EUS in evaluating lymph node metastases was 71%, with a negative predictive value of 84%. Endoscopic ultrasound accuracy in differentiating mucosal from submucosal lesions increased from the lower esophagus or gastroesophageal junction to the mid and upper esophagus (71%, 76%, and 100%, respectively; not significant). As for the histologic type, accuracy was 70% for adenocarcinoma and 81% for squamous cell carcinoma, (not significant); for lesions detected as type 0-IIa (13 patients), accuracy was 100%; for type 0-I lesions (23 patients), accuracy was 70% ( p = 0.03). Conclusions Despite difficulties in differentiating mucosal from submucosal lesions, even with 20-MHz miniprobes, EUS remains an extremely valuable tool when nonsurgical treatments are considered. Its staging accuracy depends on site and macroscopic appearance of the neoplasm.
Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G ...contributed analytic tools; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C analyzed the data; Diamantis G and Scarpa M wrote the paper; all authors revised and approved the final version of the manuscript.
Posterior reversible encephalopathy syndrome is a rare syndrome characterized by brain edema and neurological symptoms, often resulting from several drugs. Treatment is based on discontinuation, and ...diagnosis is thus essential. Only 13 cases of posterior reversible encephalopathy syndrome have been reported in inflammatory bowel diseases, and we present the first after azathioprine in adults. A 56-year-old patient with active ulcerative colitis was found unconscious 5 days after the institution of azathioprine. Right-sided hemiplegia was found after the patient regained consciousness. Magnetic resonance imaging showed altered signal associated with diffusion restriction in the occipital lobe and cerebral vasogenic edema. Complete regression of neurological signs occurred after azathioprine discontinuation.
Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often ...unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2 , ABCC3 , CYP2A6 , PPARG , and SLC7A8 genes was greater than that of clinical factors alone (area under the curve AUC = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.
Brunner’s gland hamartoma (BGH) is an uncommon benign tumor arising from alkaline-based mucin-secreting glands of the duodenum. These lesions are typically discovered incidentally during upper ...gastrointestinal endoscopy or radiological diagnostics, even though they can eventually lead (in the case of increasing size) to obstructive or hemorrhagic symptoms. We report the case of a 67-year-old Caucasian man with two episodes of melena and epigastric pain during the last month. Esophagogastroduodenoscopy revealed a large pedunculated and eroded polyp inside the antrum with a 2-cm-long stalk arising from the anterior wall of the duodenal bulb. Endoscopic ultrasonography showed a submucosal lesion with homogeneous hyperechoic parietal thickening and some central gaps. The muscularis was undamaged. No lymphadenopathy was observed. We performed an en bloc endoscopic resection of the polyp. The size of the whole piece was approximately 6 × 3 × 2 cm, pseudocapsulated and tough in consistency. In the case presented, the en bloc endoscopic removal was successful despite the size of the tumor.
Background and Aim: Contrast harmonic endoscopic ultrasound (CH‐EUS) was recently introduced to clinical practice; its reproducibility among endosonographers is unknown. Our aim was to assess the ...interobserver agreement (IA) in CH‐EUS.
Methods: Fifteen endosonographers (eight experienced and seven non‐experienced) from 11 Italian EUS centers evaluated 80 video‐cases (40 solid pancreatic lesions, 20 pancreatic cystic lesions and 20 submucosal lesions) of CH‐EUS, according to the degree of enhancement, the pattern of distribution and the washout of the contrast agent. IA within each group and between the two groups of observers was assessed with the Fleiss kappa statistic.
Results: Overall IA was moderate for the uptake and fair for the pattern of distribution and the washout. In solid pancreatic lesions, IA was moderate for the uptake and fair for the pattern and the washout. In cystic pancreatic lesions, IA was uniformly moderate for the assessment of uptake, slight for the pattern and fair for the washout. In submucosal tumors, IA was substantial for the uptake, slight for the pattern and fair for the washout. Non‐experienced endosonographers demonstrated, in most cases, comparable IA with the experienced ones.
Conclusions: Interobserver agreement among endosonographers for CH EUS was satisfactory. In particular, overall IA varied from slight to substantial, being fair in the majority of cases. Inherent structural features of the lesions, as well as technical differences between the variables assessed, could have accounted for the fluctuation of the results. Outcomes of IA were reproducible between experienced and non‐experienced endosonographers.
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