Analysis of patients attitude to undergo urgent endoscopic procedures during COVID-19 outbreak in Italy.

We conducted a survey to investigate to what extent the fear of COVID-19 has influenced the patients decision to undergo or to cancel endoscopic procedures. We collected data from 847 patients from 13 centres. The main indication for endoscopy was anemia, followed by pain and unexplained weight loss. The percentage of not presenters progressively increased throughout the three weeks of study, from 15.1% at the beginning to 48.2% at the end. 37 (34.2%) upper GI endoscopies and 112 (56.3 %) colonoscopies showed an organic cause explaining the symptoms presented by the patients, respectively; 5 cases of gastric cancer (4.6%) and 16 cases of colorectal cancer (CRC) (6.0%), respectively, were detected; during the second week the percentage of organic diseases found at upper endoscopy was 19 (33.3%) with 5 cancer (8.7%), and 61 (49.1% ) at colonoscopy, with 2 CRC (1.6%); finally, during the third week the corresponding figures were 19 (48.7%) for upper GI examinations, with 3 gastric cancers (7.7%), and 43 (60.5%) with 4 (6.5%) CRC cases found.We conclude that patients weighted the fear of having a clinically relevant disease with the fear of becoming infected by coronavirus, and a relevant percentage of them (29.4%) decided not to attend the endoscopy suites at the scheduled date.

µMAPPS: a novel phasor approach to second harmonic analysis for in vitro-in vivo investigation of collagen microstructure.

Second Harmonic Generation (SHG) is a label-free imaging method used to monitor collagen organization in tissues. Due to its sensitivity to the incident polarization, it provides microstructural information otherwise unreachable by other intensity based imaging methods. We develop and test a Microscopic Multiparametric Analysis by Phasor projection of Polarization-dependent SHG (µMAPPS) that maps the features of the collagen architecture in tissues at the micrometer scale. µMAPPS retrieves pixel-by-pixel the collagen fibrils anisotropy and orientation by operating directly on two coupled phasor spaces, avoiding direct fitting of the polarization dependent SHG signal. We apply µMAPPS to fixed tissue sections and to the study of the collagen microscopic organization in tumors ex-vivo and in-vivo. We develop a clustering algorithm to automatically group pixels with similar microstructural features. µMAPPS can perform fast analyses of tissues and opens to future applications for in-situ diagnosis of pathologies and diseases that could assist histo-pathological evaluation.

Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme.

OBJECTIVE: Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). The present study was aimed at evaluating whether a split regimen was superior to the traditional 'full-dose, day-before' regimen in terms of ADR. DESIGN: In a multicentre, randomised, endoscopist-blinded study, 50-69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to receive low-volume 2-L polyethylene glycol (PEG)-ascorbate solution in a 'split-dose' (Split-Dose Group, SDG) or 'day-before' regimen (Day-Before Group, DBG). The primary endpoint was the proportion of subjects with at least one adenoma. Secondary endpoints were the detection rates of advanced adenomas and serrated lesions at per-patient analysis and the total number of lesions. RESULTS: 690 subjects were included in the study. At per-patient analysis, the proportion of subjects with at least one adenoma was significantly higher in the SDG than in the DBG (183/345, 53.0% vs 141/345, 40.9%, relative risk (RR) 1.22, 95% CI 1.03 to 1.46); corresponding figures for advanced adenomas were 26.4% (91/345) versus 20.0% (69/345, RR 1.35, 95% CI 1.06 to 1.73). At per-polyp analysis, the total numbers of both adenomas and advanced adenomas per subject were significantly higher in the SDG (1.15 vs 0.8, p <0.001; 0.36 vs 0.22, p<0.001). CONCLUSIONS: In an organised screening setting, the adoption of a split regimen resulted into a higher detection rate of clinically relevant neoplastic lesions, thus improving the effectiveness of colonoscopy. Based on such evidence, the adoption of a split regimen for colonoscopy should be strongly recommended. CLINICAL TRIAL REGISTRATION NUMBER: NCT02178033.

Barriers against split-dose bowel preparation for colonoscopy.

OBJECTIVE: Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake. DESIGN: In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. RESULTS: Of the 1447 patients (mean age 59.2±13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, χ2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). CONCLUSION: Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. TRIAL REGISTRATION NUMBER: NCT02287051; pre-result.

Anastomotic leakage following colorectal resection for cancer: how to define, manage and treat it.

AIM: Aim of the study was to report the experience of a single center in the surgical treatment of anastomotic leak after colorectal resection for cancer, focusing on its incidence, diagnosis and management, with particular attention to surgical options. METHODS: Demograhic and clinical data from 1284 consecutive patients operated on for colorectal cancer during a period of 11 years, were prospectively collected and inserted into an electronic database. For the purpose of the study, only patients in whom an anastomosis was performed were considered. Therefore, 128 patients (9.9%) were excluded and 1156 represent the study population. All complications occurring after surgery were systematically recorded. The incidence of colorectal anastomotic leak (CAL), its management and outcome was analyzed. RESULTS: An ileo-colic anastomosis was performed in 426 cases (36.8%), ileo-rectal in 29 (2.5%), colo-colic in 409 (35.4), colo-rectal with partial mesorectal excision in 211 (18.3%) and lower colorectal or coloanal anastomosis with total mesorectal excision and temporary loop ileostomy in 81 (7%). Colorectal anastomotic leak occurred in 78/1156 patients (6.7%), accounting for 19% of overall complications. Thirty-six out of 78 patients (46.2%) were successfully treated conservatively, whereas 42 (53.8%) underwent re-operation. Nine out of 78 patients (11.5%) with CAL died owing to an uncontrolled sepsis. All had undergone previous re-intervention, with a post-operative mortality rate of 21.4% (9 out of 42). CONCLUSION: Mortality rate in patients undergoing re-operation for colorectal anastomotic leakeage is still high, and accounts for up to 40% of the deaths after colorectal resection for cancer. In the light of these data, strategic clinical decisions are mandatory to optimize the selection of patients who need an early and fast surgical approach. What does this paper add to the literature? Systematic and prospective data recording is an essential tool to assess the quality of healthcare and to plan quality improvement programs. Every effort should be done to reach an early diagnosis of CAL, possibly in a pre-clinical phase in which non clinical methods could be used to predict it.

Efficacy and acceptability of sodium picosulphate/magnesium citrate vs low-volume polyethylene glycol plus ascorbic acid for colon cleansing: a randomized controlled trial.

AIM: The study compared the efficacy, safety and tolerability of a low-volume picosulphate/magnesium citrate preparation with that of polyethylene glycol plus ascorbic acid (PEG + ASC) in a randomized clinical trial (RCT). METHOD: A multicentre randomized, single-blinded study was designed. Adult outpatients undergoing colonoscopy received either picosulphate/magnesium citrate (Group 1) or PEG + ASC (Group 2). Bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS) and rated as adequate if ≥ 2 in each segment. Patient acceptance, satisfaction and related symptoms were recorded. RESULTS: Two-hundred and eighty-five patients were included. Preparation was adequate in 75.7% of patients in Group 1 and in 76.5% of patients in Group 2. The mean BBPS scores for the entire colon and for the right colon were comparable between groups. In addition, 97.1% patients in Group 1 and 84.8% in Group 2 reported no or mild discomfort (P < 0.0003) and 97.8% and 83.4% expressed their willingness to repeat the preparation (P < 0.0001). Palatability was better in Group 1, whereas related symptoms occurred more frequently in Group 2. Regardless of which preparation was used, the split regimen was associated with better cleansing compared with the same-day method (OR = 3.39; 95% CI: 1.1-10.4; P = 0.03). Other predictors of poor cleansing were comorbidity, discomfort during preparation and incomplete (< 75%) preparation. CONCLUSION: Both picosulphate/magnesium citrate and PEG + ASC are effective for bowel preparation. Tolerability and palatability are better for picosulphate/magnesium citrate. A split schedule is associated with higher cleansing quality also for low-volume regimens.

Warm water infusion colonoscopy: a review and meta-analysis.

BACKGROUND AND STUDY AIMS: Warm water infusion instead of traditional air insufflation during the insertion phase of colonoscopy has been proposed to reduce pain and improve patient acceptance of the procedure. This systematic review aimed to compare warm water infusion with standard air insufflation according to findings from randomized controlled trials (RCTs). METHODS: In a systematic review and meta-analysis of RCTs comparing warm water infusion with standard air insufflation, primary outcome measures were procedure-related (cecal intubation, time to cecal intubation, and adenoma detection rates) and patient-related (pain). RESULTS: Nine studies (1283 patients) were included. Warm water infusion, as sole modality for facilitating insertion, was associated with a fourfold higher risk of cecal intubation failure compared with air insufflation (risk ratio [RR] 4.01, confidence interval [CI] 1.17 to 13.78, P = 0.03), but this risk did not significantly differ between warm water infusion and air insufflation with the hybrid technique (i. e., brief use of air when difficulty, e. g. poor view, was encountered). Warm water infusion and air insufflation were associated with similar cecal intubation times (P = 0.62) and adenoma detection rates (P = 0.49), but with warm water infusion patients experienced significantly less pain (P < 0.00001) and a significantly lower proportion requested sedation and/or analgesia (RR 0.48, CI 0.35 to 0.66, P < 0.00001). CONCLUSIONS: Although failure of cecal intubation is more frequent with warm water infusion, technical modifications, i. e., short air insufflations, can abolish this. Warm water infusion is less painful than standard air insufflation, reduces the need for sedation/analgesia, and improves patient acceptance of colonoscopy, without additional adverse reactions.

Resect and discard strategy in clinical practice: a prospective cohort study.

BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps. In patients with small polyps (< 10  mm), the application of NBI within a "resect and discard" strategy, might allow post-polypectomy surveillance intervals to be determined independently from histopathology. The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice. PATIENTS AND METHODS: Consecutive colonoscopy outpatients with one or more polyps smaller than 10  mm were prospectively included. Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria, and future post-polypectomy surveillance interval was assigned accordingly. Following histopathology, post-polypectomy surveillance interval was subsequently re-assigned, and the accordance between endoscopy- and histology-directed surveillance strategies was calculated. RESULTS: Among 942 colonoscopy patients, 286 (30.4 %) with only small polyps were included. In total, 511 small polyps were evaluated; 350 (68.5 %) were adenomas and 18 of these (5.1 %) had histologic features of advanced neoplasia. For the in vivo diagnosis of adenoma, NBI sensitivity, specificity, accuracy, and positive and negative likelihood ratios were 94.9 %, 65.8 %, 85.7 %, 2.80, and 0.08, respectively. The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients (82.9 %). In 9.8 % and 7.3 % patients, the endoscopy-directed approach would have resulted in early and delayed surveillance, respectively. CONCLUSIONS: The resect and discard strategy seems to be a viable, safe, and cost-effective approach for the management of patients with small polyps. However, caution in the application of the strategy should be advocated for patients with polyps 6 - 9  mm in size and those with right-sided lesions, due to their malignant potential. The study was registered on Clinicaltrials.gov (NCT01462123).

Removal of infused water predominantly during insertion (water exchange) is consistently associated with a greater reduction of pain score - review of randomized controlled trials (RCTs) of water method colonoscopy.

INTRODUCTION: Variation in the outcomes in RcTs comparing water-related methods and air insufflation during the insertion phase of colonoscopy raises challenging questions regarding the approach. This report reviews the impact of water exchange on the variation in attenuation of pain during colonoscopy by water-related methods. METHODS: Medline (2008 to 2011) searches, abstracts of the 2011 Digestive Disease Week (DDW) and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of the colonoscope. Results: Since 2008 nine published and one submitted RcTs and five abstracts of RcTs presented at the 2011 DDW have been identified. Thirteen RcTs (nine published, one submitted and one abstract, n=1850) described reduction of pain score during or after colonoscopy (eleven reported statistical significance); the remaining reports described lower doses of medication used, or lower proportion of patients experiencing severe pain in colonoscopy performed with water-related methods compared with air insufflation (Tables 1 and 2). The water-related methods notably differ in the timing of removal of the infused water - predominantly during insertion (water exchange) versus predominantly during withdrawal (water immersion). Use of water exchange was consistently associated with a greater attenuation of pain score in patients who did not receive full sedation (Table 3). CONCLUSION: The comparative data reveal that a greater attenuation of pain was associated with water exchange than water immersion during insertion. The intriguing results should be subjected to further evaluation by additional RcTs to elucidate the mechanism of the pain-alleviating impact of the water method.

Removal of infused water predominantly during insertion (water exchange) is consistently associated with an increase in adenoma detection rate - review of data in randomized controlled trials (RCTs) of water-related methods.

INTRODUCTION: Variation in outcomes in RcTs comparing water-related methods and air insufflation raises challenging questions regarding the new approach. This report reviews impact of water exchange - simultaneous infusion and removal of infused water during insertion on adenoma detection rate (ADR) defined as proportion of patients with a least one adenoma of any size. METHODS: Medline (2008-2011) searches, abstract of 2011 Digestive Disease Week (DDW) meeting and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of colonoscope. RESULTS: Since 2008, eleven reports of RcTs (6 published, 1 submitted and 4 abstracts, n=1728) described ADR in patients randomized to be examined by air and water-related methods. The water-related methods differed in timing of removal of the infused water -predominantly during insertion (water exchange) (n=825) or predominantly during withdrawal (water immersion) (n=903). Water immersion was associated with both increases and decreases in ADR compared to respective air method patients and the net overall change (-7%) was significant. On the other hand water exchange was associated with increases in ADR consistently and the net changes (overall, 8%; proximal overall, 11%; and proximal <10 mm, 12%) were all significant. CONCLUSION: Comparative data generated the hypothesis that significantly larger increases in overall and proximal colon ADRs were associated with water exchange than water immersion or air insufflation during insertion. The hypothesis should be evaluated by RCTs to elucidate the mechanism of water exchange on adenoma detection.

Colonoscopy practice in Italy: a prospective survey on behalf of the Italian Association of Hospital Gastroenterologists.

BACKGROUND: Examining the current practice is important for the benchmarking of quality of colonoscopy and the comparison with the standards and recommendations expected by professional societies. AIM: To describe colonoscopy practice in Italy, on the basis of prospective analysis of a large number of examinations performed by operators with different levels of expertise in a wide range of unselected centres. DESIGN AND SETTING: Cross-sectional, prospective and multicentre study. METHODS: The main features of each endoscopy centre (structure indicators) were collected through the use of a standardised questionnaire. A second questionnaire was used to prospectively record details of all the consecutive colonoscopies performed in a 2-week study period. RESULTS: Data from 278 centres and 12,835 consecutive colonoscopies were evaluated. Centres were uniformly distributed throughout Italy - north, centre and south - as was their organizational complexity and workload. Overall, adequate facilities (i.e. cleaning area for disinfection/reprocessing, equipped recovery room), and safety equipment (i.e. pulse oximetry, equipment for emergency cardiopulmonary resuscitation) were lacking in a considerable amount of centres, especially in those with a lower degree of organizational complexity. Written informed consent was routinely required in 87% of the centres, but a specific consent for colonoscopy, including detailed information on adverse events, was adopted by 66%. Regular programs for recording some quality indicators (i.e. cecal intubation, quality of bowel cleansing, patients' satisfaction and complications) were implemented in a minority of centres. About 93% of the colonoscopies were performed for diagnostic purpose; screening and surveillance accounted for 13.7% and 25.3% of the indications, respectively. Sedation and/or analgesia was administered in about half of the patients. Overall, colonoscopies were completed to the cecum in 80.7% of cases, and only 22.1% of the centres reported a cecal intubation rate >or=90%; this figure was reported in 33.1% of centres with high-organizational complexity and in 14.4% of outpatient units. The overall incidence of immediate complications was low (2 perforations, 26 bleedings and 32 serious cardiorespiratory complications). CONCLUSIONS: This study documented a wide variation in colonoscopy practice between centres and highlighted problem areas where interventions are needed to improve performance and safety of the examinations.

Effectiveness of a continuous quality improvement program on colonoscopy practice.

BACKGROUND AND STUDY AIM: Continuous quality improvement (CQI) is recommended by professional societies as part of every colonoscopy program, but little is known with regard to its effectiveness for colonoscopy outcomes. We prospectively assessed whether the implementation of a CQI program in routine clinical practice influences the quality performance of colonoscopy. METHODS: In an open-access endoscopy unit at a secondary care center in Northern Italy, 6-monthly audit cycles were carried out over a 4-year period, to identify reasons for poor colonoscopy outcomes and institute appropriate changes to improve performance. The colonoscopy completion rate and the polyp detection rate as detected by endoscopists were considered to be key measures for improvement. RESULTS: The initial crude colonoscopy completion rate was 84.6%, with a range for individual endoscopists 80.4%-94%. Four endoscopists had a completion rate lower than 90%. The overall polyp detection rate was 34%, with a wide variation among endoscopists (range 14%-42%). Poor patient tolerance and differences in colonoscopist expertise were the main determinants of lack of completion and variation in polyp detection rate. Changes to sedation practice, greater access to endoscopy sessions for the endoscopists with the lowest performance rates, and other organizational arrangements, were implemented to improve quality performance. The crude completion rates improved consistently, up to 93.1%, over the study period. This trend was confirmed even when adjusted completion rates were calculated. All endoscopists reached a crude completion rate of 90% or more and a polyp detection rate of over 20%. The introduction of CQI did not significantly change the overall incidence of procedure-related complications. CONCLUSIONS: The effectiveness of colonoscopy can be improved by implementing a CQI program in routine colonoscopy practice.

Increased prevalence of migraine in patients with uninvestigated dyspepsia referred for open-access upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: The association between gastrointestinal symptoms and headache is frequently unrecognized. The aim of the present study was to determine the prevalence of migraine in dyspeptic outpatients referred for upper gastrointestinal endoscopy. PATIENTS AND METHODS: Patients aged 18 - 55 years undergoing upper gastrointestinal endoscopy for dyspeptic symptoms in three endoscopic units were recruited consecutively. All of the patients were given a validated questionnaire on headache symptoms in order to determine the prevalence of migraine. Patients were divided into four groups (ulcer-like dyspepsia, reflux-like dyspepsia, dysmotility-like dyspepsia, only nausea and/or vomiting). Age-matched blood donors were given the same questionnaires and served as controls. RESULTS: A total of 378 patients (mean age 40 +/- 11, 52 % men) and 310 controls (mean age 39 +/- 11, 56 % men) were enrolled. No differences were observed between the two groups in the prevalence of migraine (15 % vs. 11 %; P = 0.12). A higher prevalence of migraine was found among women in both groups (P < 0.006). In patients with reflux-like and ulcer-like dyspepsia, the prevalence of migraine did not differ from that in the control individuals (8 % and 7 %, respectively), whereas a higher prevalence of migraine was noted in patients with dysmotility-like dyspepsia (23 %; P < 0.02 vs. controls, those with ulcer-like dyspepsia and those with reflux-like dyspepsia) and in patients with nausea and/or vomiting alone (53 %; P < 0.002 vs. all other groups). The multivariate analysis confirmed that the symptom pattern and sex were the only variables independently associated with migraine. CONCLUSIONS: A diagnosis of migraine should be considered in young patients referred for upper gastrointestinal endoscopy due to nausea and/or vomiting or for dysmotility-like dyspepsia.

Routine versus "on demand" sedation and analgesia for colonoscopy: a prospective randomized controlled trial.

BACKGROUND: The safety and tolerance of routine sedation and analgesia versus "on demand" sedation were compared in patients undergoing colonoscopy. METHODS: Two hundred forty-nine outpatients were randomly assigned to one of two groups. Group A (n = 125) received midazolam, 0.07 mg/kg intravenously plus meperidine, 0.77 mg/kg intravenously immediately preceding the colonoscope insertion. Group B (n = 124) received the same medication upon request during the procedure. Tolerance was assessed 24 hours later by phone interview performed by a nurse blinded to the medication regimen administered. RESULTS: Eighty-three patients (66%) in Group B required sedation during colonoscopy. Among men in Group B more than 60 years of age, only 23% required sedation. The proportion of patients reporting moderate or severe pain (34% vs. 12.1%, p < 0.001) and of those stating they would not be willing to undergo colonoscopy again in the future (22% vs. 9.7%, p < 0.005) was significantly higher in the "on demand" sedation group. By multivariate analysis the randomization group was the single variable independently associated with both such outcomes. The frequency of side effects was similar in the two groups. CONCLUSIONS: Administration of sedative and analgesic drugs routinely before colonoscopy is superior to "on demand" sedation in terms of tolerance and is not associated with an increase in side effects.

Hepatocyte proliferation and risk of hepatocellular carcinoma in cirrhotic patients.

OBJECTIVES: High hepatocyte proliferation has been recently proposed as a risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess whether hepatocyte proliferation is an independent risk factor for HCC when considered together with clinical and demographic characteristics. METHODS: We retrospectively evaluated 97 consecutive patients with a histological diagnosis of cirrhosis and preserved liver function, enrolled in a surveillance program for early diagnosis of HCC. Hepatocyte proliferation was evaluated by flow-cytometric analysis in liver samples collected at the time of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum alpha-fetoprotein (AFP) assays every 6 months. RESULTS: During a mean follow-up of 53 months (range, 12-120 months), 12 patients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5%+/-1.6 in patients who developed HCC and 0.9%+/-0.6 in those who did not (p < 0.0001). By univariate analysis, S-phase fraction 1.8% or higher and AFP higher than 20 ng/ml were the only two variables significantly correlated with the development of HCC (p < 0.0001, p < 0.0001). Multivariate analysis found that both variables were independently associated with HCC development (p < 0.003 and p < 0.005, respectively), with hazard ratios of 8.0 and 7.3 (confidence intervals, 2.1-31.2 and 1.8-29.2). Among patients with high AFP and/or high S-phase fraction, 11 (39%) developed HCC, compared with only one (1%) with a low S-phase fraction and normal AFP, corresponding to HCC yearly incidences of 9.5% and 0.3% (p < 0.00009). CONCLUSIONS: Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surveillance program.