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Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607-0.682), 0.670 (0.626-0.714) and 0.682 (0.580-0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.

Background The SARS-CoV-2 pandemic has had a huge impact on healthcare systems, resulting in many routine diagnostic procedures either being halted or postponed. Aims To evaluate whether the diagnoses of colorectal, gastric and pancreatic cancers have been impacted by the SARS-CoV-2 pandemic in Italy. Methods A survey designed to collect the number of histologically-proven diagnoses of the three cancers in gastroenterology services across Italy from January 1 to October 31 in 2017–2020. Non-parametric ANOVA for repeated measurements was applied to compare distributions by years and macro-areas. Results Compared to 2019, in 2020 gastric cancer diagnoses decreased by 15.9%, CRC by 11.9% and pancreatic by 9.9%. CRC distributions showed significant differences between all years, stomach cancer between 2018 and 2020 and 2019–2020, and pancreatic cancer only between 2017 and 2019. The 2019–2020 comparison showed fewer CRC diagnoses in the North (-13.7%), Center (-16.5%) and South (-4.1%), fewer stomach cancers in the North (-19.0%) and South (-9.4%), and fewer pancreatic cancers in the North (-14.1%) and Center (-4.7%), with an increase in the South (+12.3%). Distributions of CRC and gastric cancer were significantly different between all years in the North. Conclusions This survey highlights the concerning effects of the COVID-19 pandemic on the diagnostic yield of gastroenterology services for stomach, colorectal and pancreatic cancers in Italy.

To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy.Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure.A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes.Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy.

Laser energy can be used for a variety of neoplastic diseases including benign tumors, early stage malignancies, and advanced carcinomas, either with curative intent or for palliation. Nd:YAG laser photocoagulation of 168 colorectal adenomas allowed a complete eradication in 70% of cases, after a mean follow-up of 22 months. Advanced and obstructing tumors were treated with Nd:YAG laser to recanalize the lumen. In the upper gastrointestinal tract the recanalization of the lumen by means of laser photocoagulation improved the quality of life and survival. In fact, in our series of 308 patients treated, 1-year survival was 23% in recanalized patients and 7% in nonrecanalized patients. In the lower gastrointestinal tract, 289 cancer patients were treated and an amelioration of symptoms related to the obstruction was obtained in 93%). The current indication for photodynamic therapy is mainly the treatment of flat or ulcerative early stage tumors in the esophagus and stomach of high risk patients. Out of 17 patients treated, 14 were locally cured.

It is still not clear what is the best way of evaluating rectal bleeding in young people. Our aim was to examine the prevalence of neoplastic colonic lesions in these patients.This prospective, multicenter study enrolled 622 patients aged 30-50 yr (F 232/M 390) consecutively seen in 14 open-access endoscopy departments for hematochezia, defined as bright red blood from the rectum, red blood noted either in the feces, on toilet paper, or in the toilet bowl. At colonoscopy, pathology was stratified as either proximal or distal to the splenic flexure. Exclusion criteria were a history of colitis, colorectal cancer, polyps, anemia, significant weight loss, severe bleeding, or strong family history of colorectal cancer.Malignant polyps were found in two patients (0.6%), aged 30-40 yr, one in the rectum and one in the sigmoid. A malignant polyp of the cecum was found in a 41-yr-old patient. Another, aged 47, had a malignant granular-cell tumor of the rectum. A total of 35 advanced adenomas were identified in 18 patients. In 7 patients (2.2 %) within the 30-40 yr age bracket we found 8 advanced adenomas (all in the rectum/sigmoid). The other 27 advanced adenomas were in 11 patients (3.5%) in the 41-50 yr age bracket. In this age group we observed 3 patients with 10 isolated proximal advanced adenomas.In patients younger than 40 yr with hematochezia, advanced neoplastic lesions are rare and usually located in the rectum and sigmoid colon. Sigmoidoscopy appears to be sufficient for evaluation in these patients.

We assessed prospectively clinical and quality of life changes in 9 patients with Parkinson's disease (PD; HYor = 3) with severe motor fluctuations and dyskinesia who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy. Seven patients completed the follow-up period. Duration of "off" periods and time with disabling dyskinesia shortened significantly in all patients (P0.01). Total daily dose of levodopa infused did not differ from baseline equivalents. There were significant improvements in UPDRS-II (activities of daily living) and -IV (motor complications) in the "on" condition (P0.02), and in four PDQ-39 domains (mobility, activities of daily living, stigma, bodily discomfort; P0.05). Two patients withdrew for adverse events. Our results demonstrate that a satisfactory therapeutic window can be achieved and maintained for several months in advanced PD patients.

The main purpose of cancer therapy is to treat malignant tissue with the least damage to normal surrounding structures. Photodynamic therapy (PDT) seems to be able to fulfil this simple but fundamental premise. The mechanism of action of the photosensitizer- light system can be summarized in two main points. Chiefly, it seems to be a photodynamic process, with energy transfer from the light to the photosensitizer and from it to the oxygen molecules. Oxygen is excited and becomes singlet oxygen, which is extremely reactive and very noxious for tissues in which it develops. Secondly, a thermal mechanism related to light absorption and consequent temperature rise also seems to be involved in malignant necrosis by PDT. Thirteen males were submitted to endoscopic PDT. A total of 15 treatments were given: 2 patients were submitted to 2 sessions of PDT. Forty-eight hours after HPD administration (72 h in a few cases), the lesions were exposed to a 630 nm light from an argon-dye laser system. The total estimated energy dose delivered to the tumour surface was 90-150 J/cm 2 in 11 cases. All cases treated responded well and total disappearance was obtained. Median follow-up was 9.5 months (1-20 months) and the estimated energy delivered from 90-600 J/cm 2. No major complications were reported.

The dependence of autofluorescence properties on the excitation wavelength was studied on colon tissue, comparing neoplastic with non-neoplastic tissues. Studies were performed both on tissue sections and on whole tissue from biopsies of surgical resection, using microscopic and optic fiber devices, respectively. The excitation wavelengths 366, 405 and 436 nm, corresponding to emission lines of Mercury lamp, were considered. The results indicate that the emission intensity and spectral shape of autofluorescence of both the histological components of tissue and of the whole tissue are affected by the excitation wavelength to an extent varying with tissue condition. Excitation at 366 nm enhances the differences between non-neoplastic and neoplastic tissues in the spectral region mainly related to the tissue metabolism (NADH); excitation at 436 nm favors the differences attributable to the tissue alteration arising from tumor host-response. The findings provide useful information for optimizing autofluorescence-based technique in tumor diagnosis.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The purpose of this study was to evaluate the efficacy and safety of endoscopic Nd:YAG laser photocoagulation for the treatment of flat colorectal adenomas. From January 1982 to December 1994, 222 lesions were treated in 216 patients. Initial eradication was obtained in 96% of lesions with a diameter less than 1 cm, in 89% of lesions with a diameter between 1 and 4 cm, and in 64% of lesions with a diameter greater than 4 cm. According to the histology, a complete disappearance was obtained in 94% of tubular, in 89% of tubulovillous, and in 80% of villous adenomas. Adenomas with severe dysplasia or foci of invasive carcinoma were eradicated in 76% and in 75% of cases, respectively. During a median follow- up of 24 months (3 - 129 months), recurrences developed in 46 of the 186 initially cured lesions (25%). All recurrent lesions were submitted to Nd:YAG laser photocoagulation, obtaining eradication in 37/46 (80%) of the cases. Malignant degeneration occurred in 6% of lesions. Complications related to laser treatments were observed in 5% of patients.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Background The management of postoperative leaks into the mediastinum or pleural cavities after esophageal surgery yields unsatisfactory results. A recently described method, drainage of the mediastinum or pleural cavity through suture line defects, has been used in our department with eight patients. Methods A suction tube was advanced over an endoscopically placed guide wire into the abscess from inside the esophagus, and gentle aspiration was used to remove saliva and secretions. Intravenous antibiotics and total parenteral nutrition were also given. Results The sepsis was rapidly controlled, and the abscess cavity progressively collapsed in all cases. Seven patients recovered and were discharged 34 to 61 days after operation; one died of concomitant complications. Conclusions This method seems promising for the management of intrathoracic esophageal leaks.

In an attempt to evaluate the role of the histological and histochemical features of adenocarcinoma and normal tissue on their fluorescence spectral patterns, we developed a Monte Carlo model to simulate the fluorescence emission from tissue. According to histology, normal colon and adenocarcinoma were considered composed of three and two tissue layers, respectively (i.e., superficial epithelium, mucosa and submucosa; tumor mass and submucosa). Characterization of the fluorescence pattern of the tissue layers as well as of several histological components was performed by spectrofluorometric analysis on ex vivo samples. Results obtained from differently modelling the morphology and histological arrangement of colon suggest the following remarks. The decrease in fluorescence intensity observed in passing from normal to abnormal tissue could be ascribed mainly to a modification in morphology. When carcinomatous tissue is involved a modification in the spectral shape is also expected.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

Both 'in vivo' and 'ex vivo' spectrofluorometric studies of neoplastic and non-neoplastic mucosa of human colon have been carried out, in order to verify the potentials of tissue natural fluorescence as a possible parameter to distinguish normal from diseased tissues, Spectrofluorometric analysis performed at colonoscopy on patients affected by neoplasia, showed that adenocarcinoma, adenoma and non-neoplastic mucosa differ in the fluorescence emissions. The results have been interpreted according to the data obtained on cryostatic sections from biopsies by means of a microspectrofluorometric analysis carried out on each histological component.

In an attempt to evaluate whether induced fluorescence could be exploited to discriminate neoplastic from non-neoplastic tissue, fluorescence spectroscopy was performed at 450-800 nm on 83 biopsy specimens of colonic mucosa. Measurements showed that fluorescence spectra of adenoma, adenocarcinoma and non-neoplastic mucosa manifest dissimilar patterns. Nine variables, whose photophysical and/or biological bases need further investigation, were derived from the spectra. Discriminant functions between the groups of lesions were determined by using a stepwise discriminant analysis. The diagnostic test had a sensitivity of 80.6% and 88.2%, and a specificity of 90.5% and 95.2% in discriminating neoplastic from non-neoplastic mucosa and adenoma from non-neoplastic mucosa respectively. These results suggest that fluorescence spectroscopy has the potential to improve endoscopic diagnosis of premalignant and malignant lesions of colonic mucosa.

Three hundred eight patients with obstructing malignant tumors of the gastrointestinal tract were submitted to endoscopic Nd:YAG laser palliation. The number of sessions as well as the number of days and total energy required for initial recanalization of the stenosis were related to tumor length. Luminal patency was obtained in 94% of patients, but improved swallowing was achieved in 74% of patients. The technical success rate did not depend on tumor site, whereas functional positive results are related to the location of the stenosis, with worst results for tumors involving the upper third of the esophagus. Life-table analysis revealed that 1-year survival was 23% when a luminal patency was achieved and 7% when treatment failed.

Photodynamic therapy (PDT) is a selective, experimental treatment for solid tumors. PDT consists of the activation of a photosensitizing agent by light. The photodynamic reaction induced by light causes damage to the tissue containing the photosensitizer in the presence of oxygen. The idea of treating tumors by photosensitizers is as old as the early 1900s; already in 1903, topic application of eosin and exposition to sunlight was known to produce a response in skin tumors. Later, in 1924, Policard reported reddish fluorescence in animal and human tumors observed under Wood lamp. The presence of fluorescence was attributed to endogenous porphyrins accumulated after infection of the observed tissue by hemolytic bacteria.2 In 1942, Auler and Banzer3 reported animal tumor fluorescence after systemic administration of Hematoporphyrin (HP) and in 1960 Lipson and coworkers prepared the Hematoporphyrine derivative (HPD), a mixture of porphyrins obtained by treating HP with acetic and sulphuric acids.4 They demonstrated that HPD was selectively accumulated by malignant as well as by actively proliferating tissues and produced the first demonstration of endoscopic diagnosis of malignant tissues by detection of fluorescence in the respiratory and in the upper digestive tract.5 After the development of the laser, diagnosis through fluorescence and particularly PDT have been studied further.

Intravenously injected haematoporphyrin derivative localizes in malignant tissue more than it does in the surrounding normal tissues; this allows cancer to be treated photodynamically. The aim of this study is to determine whether adenomas of the large bowel, which are benign precarcinomatous lesions, accumulate HPD as well as does malignant tissue, and whether such accumulation occurs to a greater extent than it does in the surrounding normal mucosa. For this purpose, microspectrofluorometric analysis was performed on biopsy samples of adenomas, on adenocarcinomas, and on normal mucosa, and the data were compared. The samples were obtained from patients affected by histologically proven adenocarcinomas and synchronous adenomas of the bowel 48h after intravenous injection of HPD (3 mg/kg bodyweight), that is, the time interval usually required for photodynamic therapy. The intensity of fluorescence of the adenomas was a little lower than that observed from adenocarcinomas, but was higher than that from the surrounding mucosa. The fluorescence spectra from adenomas and from adenocarcinomas showed three main emission bands centred at about 630, 670 and 700 nm. The relative amplitudes of the band at 630 and 670 nm in benign and malignant colorectal tumours varied with the excitation wavelength, depending on the different physicochemical state of the accumulated drug. A further analysis, performed 72 h after administration, indicated the existence of an intratissue turnover of the porphyrins.