A multicenter randomized phase 4 trial comparing sodium picosulphate plus magnesium citrate vs. polyethylene glycol plus ascorbic acid for bowel preparation before colonoscopy. The PRECOL trial.

Background: Adequate bowel preparation before colonoscopy is crucial. Unfortunately, 25% of colonoscopies have inadequate bowel cleansing. From a patient perspective, bowel preparation is the main obstacle to colonoscopy. Several low-volume bowel preparations have been formulated to provide more tolerable purgative solutions without loss of efficacy. Objectives: Investigate efficacy, safety, and tolerability of Sodium Picosulphate plus Magnesium Citrate (SPMC) vs. Polyethylene Glycol plus Ascorbic Acid (PEG-ASC) solutions in patients undergoing diagnostic colonoscopy. Materials and methods: In this phase 4, randomized, multicenter, two-arm trial, adult outpatients received either SPMC or PEG-ASC for bowel preparation before colonoscopy. The primary aims were quality of bowel cleansing (primary endpoint scored according to Boston Bowel Preparation Scale) and patient acceptance (measured with six visual analogue scales). The study was open for treatment assignment and blinded for primary endpoint assessment. This was done independently with videotaped colonoscopies reviewed by two endoscopists unaware of study arms. A sample size of 525 patients was calculated to recognize a difference of 10% in the proportion of successes between the arms with a two-sided alpha error of 0.05 and 90% statistical power. Results: Overall 550 subjects (279 assigned to PEG-ASC and 271 assigned to SPMC) represented the analysis population. There was no statistically significant difference in success rate according to BBPS: 94.4% with PEG-ASC and 95.7% with SPMC (P = 0.49). Acceptance and willing to repeat colonoscopy were significantly better for SPMC with all the scales. Compliance was less than full in 6.6 and 9.9% of cases with PEG-ASC and SPMC, respectively (P = 0.17). Nausea and meteorism were significantly more bothersome with PEG-ASC than SPMC. There were no serious adverse events in either group. Conclusion: SPMC and PEG-ASC are not different in terms of efficacy, but SPMC is better tolerated than PEG-ASC. SPMC could be an alternative to low-volume PEG based purgative solutions for bowel preparation. Clinical trial registration: [ClinicalTrials.gov], Identifier [NCT01649674 and EudraCT 2011-000587-10].

Surgery has a key role for quality assurance of colorectal cancer screening programs: impact of the third level multidisciplinary team on lymph nodal staging.

PURPOSE: From 2011 to 2013 in the area of the Naples 3 public health district (ASL-NA3), a colorectal cancer screening program (CCSP) was developed. In order to stress the need of quality assurance procedures for surgery and pathology, a third level oncologic pathway was added and set up at a referral colorectal cancer center (RC). Lymph nodal (LN) harvesting, as a process indicator, and nodal positivity were adopted for an interim analysis. METHODS: The program was implemented by a series of audit meetings and a double type of multidisciplinary team (MDT): "horizontal" and "vertical." Three hundred and forty colorectal cancer (CRC) patients underwent surgery: 119 chose to be operated at the RC (Gr In), 65 were operated at 22 district hospitals (DH) (Gr Out), and 156 symptomatic not screened patients were operated at the RC (Gr Sym). RESULTS: Statistical analysis revealed differences between Gr In and Gr Out colon groups both for LN harvesting (median of 26 and 11, respectively, P = 0.0001), and for nodal positivity after the first screening round (34.78 and 19.45%, respectively, P = 0.0169). Results were all the more significant in a subset analysis on early T stage colon subgroups (In vs Out) both for LN harvesting (P < 0.0001) and nodal positivity (P < 0.0001). CONCLUSION: xSignificant differences between RC and DHs were found, particularly for early-stage CRC patients. LN harvesting should be considered as a surrogate marker of quality assurance for at least screening hospitals for "minimum best" standard of care. This should lead to set up a third level in any CCSP.

Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer.

The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery.

Endoscopic surveillance for hereditary non-polyposis colorectal cancer (HNPCC) family members in a Southern Italian region.

BACKGROUND: Surveillance in hereditary non-polyposis colorectal cancer (HNPCC) family members recommends baseline colonoscopy starting at age 20 and then surveillance colonoscopy every 1-2 years. AIMS: To verify adherence to the guidelines for HNPCC family members enrolled in endoscopic surveillance. METHODS: Data regarding 11 HNPCC families was retrieved from our database. Excluding 11 probands, 106 family members were evaluated and 40 underwent surveillance. RESULTS: At baseline colonoscopy, 7 colorectal cancers (CRC), 14 polyps (PO) [1 inflammatory, 2 hyperplastic, 10 adenomas with low grade dysplasia (LGD-AD) and 1 adenoma with high-grade dysplasia (HGD-AD)] were diagnosed in sixteen individuals. Twenty-eight HNPCC family members underwent endoscopic surveillance, with a total of 94 surveillance colonoscopies. Of these, 45 were positive (4 CRC, 3 inflammatory PO, 34 hyperplastic PO, 21 LGD-AD and 5 HGD-AD). Mean time between two consecutive surveillance colonoscopies was 24.6 months (range 4-168). Median time to first positive surveillance colonoscopy was 84 months for HNPCC family members with negative baseline colonoscopy, and 60 months for those with positive baseline colonoscopy (p=0.21). CONCLUSIONS: Our data suggests that surveillance colonoscopy every 2 years is adequate to diagnose advanced lesions in HNPCC family members, and improves their compliance with surveillance.

Awake single-access (uniportal) video-assisted thoracoscopic surgery for peripheral pulmonary nodules in a complete ambulatory setting.

PURPOSE: Traditional 3-port video-assisted thoracoscopic surgery (VATS) in a patient who is awake has been proposed as a breakthrough in the direction of fast tracking patients through routine thoracic surgical procedures. We wanted to explore the possibility of further reducing surgical invasiveness by resecting a peripheral pulmonary nodule with single-access (uniportal) VATS in an awake, nonintubated, nonventilated patient, with selective occlusion of the tributary lobar bronchus. DESCRIPTION: A 47-year-old woman with bilateral peripheral nodules underwent uniportal VATS wedge resection of an undetermined nodule in the right middle lobe. The patient was awake and under mild sedation for the entire procedure. Single-shot epidural regional anesthesia was administered. Under guidance provided by a reusable, portable flexible bronchoscope, a Fogarty balloon was positioned to occlude the right middle lobe bronchus to facilitate collapse of the targeted parenchyma. At the end of the procedure, the chest drain was connected to a portable vacuum system delivering autonomous suction. EVALUATION: Awake uniportal VATS resection of peripheral nodules in selected patients is feasible and appears to be safe. Available technology may enable further reduction of costs related to length of hospitalization. CONCLUSIONS: The concept of ambulatory thoracic surgery may further evolve by utilizing uniportal VATS in an awake patient to solve the often-challenging diagnostic dilemmas represented by undetermined lung lesions.

The mutation spectrum of the APC gene in FAP patients from southern Italy: detection of known and four novel mutations.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited condition accounting for about 1% of all colorectal cancers, results from mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. The clinical spectrum and severity of FAP varies greatly with the mutation site, and both between and within families. Using the protein truncation test, single strand conformation polymorphism analysis and DNA sequencing, we identified 30 (75%) mutant alleles in 40 unrelated FAP families, for a total of 22 different APC mutations. Of these, 18 are known and 4 are novel: c.1797C>A (C599X), c.893_894delAC, (c.3225T>A; c.3226C>A) and c.4526_4527insT. Of the 30 APC gene mutations, 5 (approximately 17%) are nonsense mutations, 17 (approximately 57%) are small deletions, 5 (approximately 17%) are small insertions and 3 (approximately 10%) are complete deletions. All mutations occurred in single pedigrees, except those at codons 1061 and 1062, each found in two unrelated families, and the mutation at codon 1309 in exon 15, found in five unrelated families. About 40% of mutations, mostly small deletions and insertions, are located at repeated sequences; they promote misalignment-mediated errors in DNA replication and could represent a hot spot mutation region. This study enlarges the spectrum of APC gene mutations and sheds light on the correlation between the site of APC germline mutations and clinical manifestations of FAP.