The clinical utility of a comprehensive psychosomatic assessment in the program for colorectal cancer prevention: a cross-sectional study.

Few studies have investigated psychosocial characteristics and lifestyle behaviors of participants at programs for secondary prevention of colorectal cancer (CRC). This study aimed, through a comprehensive psychosomatic assessment based on clinimetric principles, to evaluate psychosocial characteristics and lifestyle behaviors in participants at CRC secondary prevention program, and to investigate the associations between these variables and endoscopic outcomes. In this cross-sectional study, the first 150 consecutive asymptomatic participants at the CRC prevention program who resulted positive to fecal occult blood test (FOBT) and were thus referred to colonoscopy, underwent a psychosomatic assessment including psychiatric diagnoses (DSM-5), psychosomatic syndromes (DCPR-R), psychological distress, psychological well-being and lifestyle behaviors. Whereas only 5.3% of the sample showed at least one DSM-5 diagnosis, 51.3% showed at least one DCPR syndrome, such as allostatic overload, alexithymia, Type A behavior, and demoralization. Patients affected by psychosomatic syndromes presented with significantly higher psychological distress, lower psychological well-being and unhealthy lifestyle behaviors, such as tobacco smoking and unhealthy diet, in comparison with patients without DCPR syndromes. Among endoscopic outcomes, the presence of adenomas was significantly associated with DCPR irritable mood. In a clinical context of secondary prevention addressing asymptomatic patients with positive FOBT, a comprehensive psychosomatic assessment may provide relevant clinical information for those patients who present certain psychosomatic syndromes associated with high psychological distress, impaired psychological well-being, unhealthy lifestyle behaviors and colorectal precancerous lesions. The results of the present study indicate a road to the practice of "preventive" medicine at CRC screening program.

Redesign of a GI endoscopy unit during the COVID-19 emergency: A practical model.

The pandemic diffusion of the SARS-CoV-2 infection throughout the world required measures to prevent and strategies to control the infection, as well as the reallocation of the hospital structures in order to take care of an increased number of infected patients. Endoscopy Units should be able to perform endoscopic procedures on COVID-19 infected as well as on noninfected patients. The aim of this manuscript is to propose a model for a fast reorganization of the endoscopy department environment in order to safely perform endoscopic procedures in this Pandemic COVID-19 scenario, according to the current advices given by the Scientific Societies.

The presence of rapid on-site evaluation did not increase the adequacy and diagnostic accuracy of endoscopic ultrasound-guided tissue acquisition of solid pancreatic lesions with core needle.

BACKGROUND: Rapid on-site evaluation (ROSE) improves the adequacy and accuracy of EUS-guided tissue acquisition, although it is not routinely widely available. Evidence suggested that core needles might overcome the absence of ROSE. The aim of this study was to evaluate the influence of ROSE on the adequacy and accuracy of EUS-guided tissue acquisition with core needles in patients with pancreatic solid lesions. METHODS: Patients who underwent EUS-guided tissue acquisition of pancreatic mass lesions were retrospectively identified at three tertiary referral centers and those performed with the core needle were included. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without ROSE was the primary outcome measure. The diagnostic accuracy and tissue core acquisition were the secondary outcome measures. RESULTS: A total of 333 patients with pancreatic solid mass lesions were included in the study; 140 cases sampled with ROSE and 193 cases without ROSE. The adequacy was 92.1 % in the group sampled with ROSE and 88.1 % in the group without ROSE (p = 0.227). In the ROSE group sensitivity, specificity, and accuracy were 90.7, 100 and 92.1 %, respectively. In the group without ROSE, sensitivity, specificity, and accuracy were 87.2, 100, and 88.1 %, respectively. No difference for all these figures was observed between the two groups. The tissue core was available in 61.4 and 53.4 % of cases with and without ROSE, respectively (p = 0.143). CONCLUSION: In the absence of ROSE, EUS-based tissue acquisition with Core needle should be considered since it achieves comparable tissue sampling adequacy and accuracy.

Next generation sequencing improves the accuracy of KRAS mutation analysis in endoscopic ultrasound fine needle aspiration pancreatic lesions.

The use of endoscopic ultrasonography has allowed for improved detection and pathologic analysis of fine needle aspirate material for pancreatic lesion diagnosis. The molecular analysis of KRAS has further improved the clinical sensitivity of preoperative analysis. For this reason, the use of highly analytical sensitive and specific molecular tests in the analysis of material from fine needle aspirate specimens has become of great importance. In the present study, 60 specimens from endoscopic ultrasonography fine needle aspirate were analyzed for KRAS exon 2 and exon 3 mutations, using three different techniques: Sanger sequencing, allele specific locked nucleic acid PCR and Next Generation sequencing (454 GS-Junior, Roche). Moreover, KRAS was also tested in wild-type samples, starting from DNA obtained from cytological smears after pathological evaluation. Sanger sequencing showed a clinical sensitivity for the detection of the KRAS mutation of 42.1%, allele specific locked nucleic acid of 52.8% and Next Generation of 73.7%. In two wild-type cases the re-sequencing starting from selected material allowed to detect a KRAS mutation, increasing the clinical sensitivity of next generation sequencing to 78.95%. The present study demonstrated that the performance of molecular analysis could be improved by using highly analytical sensitive techniques. The Next Generation Sequencing allowed to increase the clinical sensitivity of the test without decreasing the specificity of the analysis. Moreover we observed that it could be useful to repeat the analysis starting from selectable material, such as cytological smears to avoid false negative results.

Multiple KRAS mutations in pancreatic adenocarcinoma: molecular features of neoplastic clones indicate the selection of divergent populations of tumor cells.

KRAS is one of the most common genes mutated in pancreatic adenocarcinoma. Multiple KRAS mutations may be detected within the same pancreatic adenocarcinoma, but it is usually unclear whether the different mutations represent biologically irrelevant molecular events or whether they indicate the coexistence of distinct sizable neoplastic clones within a given tumor. We identified a case of pancreatic adenocarcinoma with 5 different mutations in the KRAS gene and have been able to characterize the allelic distribution of the KRAS mutations and the size of the neoplastic clones using allele-specific locked nucleic acid polymerase chain reaction and next-generation sequencing (454 GS-Junior). The results indicate that the tumor is composed of 5 distinct cell populations: one is KRAS G12V mutated (~38% of neoplastic cells), the second is KRAS G12V in one allele and KRAS G12D in the other (~32%), the third is KRAS G12V in one allele and KRAS G12R in the other (~24%), and the fourth is KRAS G12V in one allele and KRAS G12C in the other (~6%). The fifth clone, representing a minority of neoplastic cells, has a KRAS Q61H mutation in addition to one of the above alterations. Microsatellite analysis identified mutation of the NR21 marker out of the 13 tested, indicating that the tumor has a defect in maintaining DNA integrity different from loss of conventional DNA mismatch repair. These results are consistent with the successive selection of divergent populations of tumor cells and underscore the relevance of nucleotide instability in pancreatic adenocarcinoma.

Endoscopic ultrasound-guided drainage of pancreatic fluid collections.

Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recognized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, percutaneous and non-EUS-guided endoscopic drainage. EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to percutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct access to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the subsequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in "one step", EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.

Simultaneous EUS-FNA Diagnosis and TNM Staging of a Pancreatic Neuroendocrine Tumor in a Patient with an Unrecognized MEN Type 1.

We report the case of a woman who, during oncological followup for bronchial carcinoid (diagnosed in 2005), papillary thyroid carcinoma, and bilateral parathyroid adenoma (simultaneously diagnosed in 2007), performed a pancreatic endoscopic ultrasonography with fine needle agobiopsy (EUS-FNA) for a positron emission tomography (PET) suspicion of pancreatic and hepatic lesions; during the procedure, the pancreatic and liver lesions were confirmed, and a peripancreatic lymph node involvement was found, allowing a complete pTNM staging during the same procedure.

Very high CEA level in a large pancreatic cyst: is it a surgical indication by itself?

BACKGROUND: Pancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. METHODS: A man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). RESULTS: The patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. CONCLUSIONS: Is it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value? Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.

A comparison of uncovered metal stents for the palliation of patients with malignant biliary obstruction: nitinol vs. stainless steel.

BACKGROUND: Various types of self-expandable metal stents have been introduced for the palliation of malignant biliary obstruction. AIMS: To compare the outcomes of WallFlex™ and Wallstent™ uncovered biliary self-expandable metal stents (SEMSs) for the palliation of patients with malignant biliary obstruction. METHODS: Between October 2008 and December 2009, all SEMSs placed for malignant biliary obstruction were WallFlex™: all patients palliated were included in the study. Before October 2008, all the SEMSs placed for malignant biliary obstruction were Wallstent™, and the patients palliated from July 2007 to September 2008 were the comparative group. RESULTS: A total of 58 WallFlex™ and 54 Wallstent™ SEMSs were placed, and efficacious biliary decompression was achieved in all patients. Early complications occurred in 5 patients in the WallFlex™ group and in 3 in the Wallstent™ group (p=ns). Late complications occurred in 6 patients in the WallFlex™ group and in 16 in the Wallstent™ group (p<0.01). The overall patency of the self-expandable metal stent in the WallFlex™ and the Wallstent™ groups was similar (227 days vs. 215 days, p=ns). Mean patient survival was 242 days in the WallFlex™ group and 257 days in the Wallstent™ group (p=ns). CONCLUSIONS: We found no difference in terms of overall patency between the two types of SEMSs, but there was an increased rate of late adverse events in the Wallstent™ group.

Endoscopic ultrasound-guided fine needle aspiration with 22- and 25-gauge needles in solid pancreatic masses: a prospective comparative study with randomisation of needle sequence.

BACKGROUND: The difference in the diagnostic accuracy of 22- versus 25-gauge needles in EUS-FNA is not clear. AIMS: To compare the rates of technical success, diagnostic accuracy and complications of EUS-FNA performed with 22-gauge and 25-gauge needles on the same solid pancreatic mass. METHODS: All patients with solid pancreatic masses evaluated from September 2007 to December 2008 were enrolled and underwent EUS-FNA with both 22- and 25-gauge needles with randomisation of needle sequence. The accuracy of the EUS-FNA was determined by comparing the cytological results with the final surgical pathological diagnoses or with the results of a clinical follow-up. A cytological score with different qualitative parameters was created, and a comparison between these parameters was carried out for each needle. RESULTS: Fifty patients with 50 pancreatic masses were recruited. Technical success was 100% and no complications occurred. Diagnostic accuracy was 94% and 86% for the 25- and 22-gauge needles, respectively. Analysis of the cytological score showed a tendency towards the 25-gauge needle, although the difference was not statistically significant. CONCLUSIONS: EUS-FNA performed with 22- or 25-gauge needles had the same diagnostic accuracy. Our study results confirm a significant trend towards a better cytological diagnosis for the 25-gauge needle.

Through-the-scope large diameter self-expanding metal stent placement as a safe and effective technique for palliation of malignant colorectal obstruction: a single center experience with a long-term follow-up.

OBJECTIVE: The aim of this study was to evaluate the outcomes of through-the-scope (TTS) large diameter self-expanding metal stent (SEMS) placement for palliation of malignant colorectal obstruction. MATERIAL AND METHODS: Between January 2005 and December 2009, all patients who underwent endoscopic SEMS placement for palliation of malignant colorectal obstruction were prospectively enrolled. RESULTS: Thirty-nine patients (17M and 22F; mean age 75.9 ± 10.6 years, range 50-91) were enrolled. The most frequent location was the sigmoid colon (13 cases). The causes of obstruction were colorectal malignancy in 32 patients and extracolonic malignancy in 7. Technical success was achieved in 36/39 patients (92.3%) and clinical success in 35/39 patients (89.7%). Technical failure was related to female sex (p = 0.04) and the extracolonic etiology of the stricture (p < 0.001). There were three early complications: two procedure-related perforations successfully managed conservatively and one hemorrhage treated with APC. Early complications were related to the location of strictures at the recto-sigmoid junction (p < 0.001). Late complications occurred in 10 patients: 8 of these patients experienced occlusive symptoms (attributable to tumor ingrowth in 5 cases and stool impaction in 3 cases); the remaining 2 were one case of tumor ingrowth with sub-occlusive symptoms and hemorrhage, and one case of distal migration. There was no procedure-related mortality and all complications were managed without surgical intervention. SEMS patency duration was 236 ± 128 days (range 31-497) and mean survival of the patients was 259 ± 121 days (range, 32-511). CONCLUSIONS: In our experience, TTS large-diameter SEMS placement is a safe and effective treatment for palliation of malignant colorectal obstruction.

Efficacy, safety and outcomes of 'inject and cut' endoscopic mucosal resection for large sessile and flat colorectal polyps.

BACKGROUND AND STUDY AIMS: The study examines the outcomes of the 'inject and cut' endoscopic mucosal resection (EMR), for large sessile and flat colorectal polyps. PATIENTS AND METHODS: Between January 2006 and December 2008 all patients referred to our institution for EMR of large polyps were prospectively evaluated. The accuracy of lifting sign and the rate of en bloc and piecemeal resection, complications and recurrence were analyzed. RESULTS: A total of 157 patients with 182 lesions (median size 24.7 +/- 10.2 mm) were included in the study. The most frequent location was the sigmoid colon in 30.2%. Because of non-lifting sign, 5/182 lesions were referred to surgical resection and 177 (43 flat and 134 sessile) were resected, 79 (44.6%) en bloc and 98 (55.4%) piecemeal. There were 20 procedural (11.3%) and 2 late (1.1%) bleeding, 4 post-polypectomy syndrome (2.2%) and 2 perforations (1.1%). Bleeding was related to malignancy (p = 0.01). Intramucosal cancer was observed in 5 cases (2.8%) while invasive cancer was seen in 8 (4.5%). Malignancy was related to polyp size >or=30 mm (p = 0.002). Follow-up colonoscopy was performed in 147 patients with 172 EMR for a mean of 19.8 months. Recurrence was observed in 12/172 (6.9%) polyps. CONCLUSION: Inject and cut EMR is practical and effective with a low risk of complication and local recurrence.

Endoclip-assisted resection of large pedunculated colorectal polyps: technical aspects and outcome.

BACKGROUND: The most common complication of polypectomy is hemorrhage, and various techniques have been used to prevent this complication. AIM: This study evaluates the outcomes of endoclip-assisted polypectomy in patients with large pedunculated colorectal polyps, in comparison with a historical control group of patients treated with endoloop-assisted polypectomy. METHODS: Between January and December 2007, 32 patients with 32 large pedunculated polyps (>or=15 mm) were treated with endoclip-assisted polypectomy (group A). Between January and December 2006, 35 patients with 35 large pedunculated polyps were treated; 33 with endoloop-assisted polypectomy (control, group B) and two cases with endoclips and needle knife, which were included in group A for the analysis. RESULTS: The mean (+/- standard deviation [SD]) size of polyp head was 26.8 +/- 8.1 mm (range 15-50) in group A and 22.3 +/- 4.1 mm (range 15-30) in group B (P = 0.004). In group A, six polyps had a mean (+/-SD) head size of 40.8 +/- 5.8 mm (range 35-50) and were resected with clips and needle knife. In group A, bleeding occurred in two cases (5.9%), which were associated with the presence of cancer at histology (P = 0.006) and were managed by applying new clips. No bleeding occurred in patients of group B and no perforation and post-polypectomy syndrome occurred in either group. There were three (8.8%) cancerized adenomas in group A and one (3%) in group B. Clip application was possible in all patients, while in two cases, loop placement was impossible. CONCLUSIONS: In our experience, endoclip-assisted resection is a safe alternative to endoloop for the resection of large pedunculated colorectal polyps when endoloop placement is difficult or impossible.

Single session versus separate session endoscopic ultrasonography plus endoscopic retrograde cholangiography in patients with low to moderate risk for choledocholithiasis.

BACKGROUND AND AIM: Endoscopic ultrasonography (EUS) is a minimally invasive diagnostic tool for common bile duct stones (CBDS) and may be used to select patients for therapeutic endoscopic retrograde cholangiography (ERC). The aim of this trial is to compare, in patients with non-high-risk for CDBS, the clinical and economic impact of EUS plus ERC performed in a single endoscopic session versus EUS plus ERC in two separate sessions. METHODS: During an 11-month period, all adult patients admitted to the emergency department with suspicion of CBDS were categorized into either high-risk or non-high-risk groups, on the basis of clinical, biochemical, or transabdominal ultrasound findings. Patients in the non-high-risk group were randomized to receive EUS plus ERC in one single or in two separate sessions. RESULTS: Eighty patients were recruited and randomized. Forty patients underwent EUS plus ERC in a single session and 40 patients underwent EUS plus ERC in two separate sessions. Negative EUS examination for CBDS avoided unnecessary ERC to 33 patients. Out of 47 patients with positive EUS (25 from the single session group and 22 from the double session), ERC confirmed the presence of CBDS in 46 cases (EUS sensitivity 100% and specificity 98%). Average time of procedure and hospitalization were significantly shorter in the single session group compared to the two session group. The single session strategy was also less expensive. CONCLUSION: Endoscopic ultrasonography plus ERC with sphincterotomy and stone extraction performed during the same endoscopic session was safe and efficacious with a reduction of procedure time, hospitalization and costs.

Mutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progression.

Gene mutations in APC, K-ras, and p53 are thought to be essential events for colorectal cancer development. Recent data seem to indicate that K-ras and p53 mutations rarely co-exist in the same tumor, indicating that these alterations do not represent a synergistic evolutionary pathway. Moreover, an inverse relation between K-ras gene activation and BRAF mutations has been demonstrated, suggesting alternative pathways for colorectal cancer transformation. To reconstruct the chronological modulation of these gene mutations during cell transformation and colorectal cancer progression, mutations of p53, K-ras, and BRAF genes were analyzed by Single Strand Conformation Polymorphism (SSCP) or sequencing analysis in 100 colorectal cancer samples, evenly distributed among different Dukes' stages. We found mutations in p53, K-ras, and BRAF genes in 35%, 30%, and 4% of tumors, respectively, and observed a minimal or no co-presence of these gene alterations. Moreover, the frequency of molecular p53 mutations increased as tumor stage increased, suggesting an important role for this gene in the progression of colorectal cancer. Conversely, K-ras or BRAF genes were not related to tumor stage or location. These data seem to indicate the absence of a co-presence of the genes, highlighting the possibility of multiple pathways for colorectal tumor progression. Moreover, mutations in p53, K-ras, and BRAF are not present in about one-third of colorectal cancers and therefore other gene mutations need to be investigated to better understand molecular mechanisms at the basis of cell transformation and the progression of colorectal cancer.

Detection of colorectal cancer by a quantitative fluorescence determination of DNA amplification in stool.

DNA amplification of exfoliated cells in stool represents an inexpensive and rapid test, but has only 50% to 60% sensitivity. A new quantitative method, called fluorescence long DNA, was developed and validated in our laboratory on stool obtained from 86 patients with primary colorectal cancer and from 62 healthy individuals. It consists of the amplification of stool DNA with fluorescence primers and the quantification of the amplification using a standard curve. Results are arbitrarily expressed in nanograms. The potential of the new method compared to the conventional approach was analyzed in a subgroup of 94 individuals (56 patients and 38 healthy volunteers). In the present series, DNA amplification analysis showed a specificity of 97% and a sensitivity of only 50%. Conversely, fluorescence DNA evaluation, using the best cutoff of 25 ng, showed a sensitivity of about 76% and a specificity of 93%. Similar sensitivity was observed regardless of Dukes stage, tumor location, and size, thus also permitting the detection of early-stage tumors. The present study seems to indicate that quantitative fluorescence DNA determination in stool successfully identifies colorectal cancer patients with a sensitivity comparable, if not superior, to that of multiple gene analysis but at a lower cost and in a shorter time.