Robotic Colonoscopy and Beyond: Insights into Modern Lower Gastrointestinal Endoscopy.

Lower gastrointestinal endoscopy is considered the gold standard for the diagnosis and removal of colonic polyps. Delays in colonoscopy following a positive fecal immunochemical test increase the likelihood of advanced adenomas and colorectal cancer (CRC) occurrence. However, patients may refuse to undergo conventional colonoscopy (CC) due to fear of possible risks and pain or discomfort. In this regard, patients undergoing CC frequently require sedation to better tolerate the procedure, increasing the risk of deep sedation or other complications related to sedation. Accordingly, the use of CC as a first-line screening strategy for CRC is hampered by patients' reluctance due to its invasiveness and anxiety about possible discomfort. To overcome the limitations of CC and improve patients' compliance, several studies have investigated the use of robotic colonoscopy (RC) both in experimental models and in vivo. Self-propelling robotic colonoscopes have proven to be promising thanks to their peculiar dexterity and adaptability to the shape of the lower gastrointestinal tract, allowing a virtually painless examination of the colon. In some instances, when alternatives to CC and RC are required, barium enema (BE), computed tomographic colonography (CTC), and colon capsule endoscopy (CCE) may be options. However, BE and CTC are limited by the need for subsequent investigations whenever suspicious lesions are found. In this narrative review, we discussed the current clinical applications of RC, CTC, and CCE, as well as the advantages and disadvantages of different endoscopic procedures, with a particular focus on RC.

Transarterial radioembolization for hepatocellular carcinoma: a review.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is the second cause of death due to malignancy in the world. The treatment of HCC is complex and includes potentially curative and palliative approaches. However, both curative and palliative treatments for HCC are often associated with a not-completely favorable safety/efficacy ratio. Therefore, other treatment options appear necessary in clinical practice. Transarterial radioembolization has shown a promising efficacy in terms of disease control and is associated with a good safety profile. This review discusses the use of transarterial radioembolization in HCC, with a focus on the clinical aspects of this therapeutic strategy.

Curative therapies for hepatocellular carcinoma: an update and perspectives.

Curative treatments, including liver transplantation, surgical resection and percutaneous treatments, are the recommended therapies in BCLC-0 (Barcelona Clinic of Liver Cancer) or BCLC-A hepatocellular carcinoma (HCC). This review provides an overview of some issues of clinical importance concerning curative treatments in HCC.

Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives.

In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium(90)), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib.

Assessment of clinical and radiological response to sorafenib in hepatocellular carcinoma patients.

Sorafenib is an effective anti-angiogenic treatment for hepatocellular carcinoma (HCC). The assessment of tumor progression in patients treated with sorafenib is crucial to help identify potentially-resistant patients, avoiding unnecessary toxicities. Traditional methods to assess tumor progression are based on variations in tumor size and provide unreliable results in patients treated with sorafenib. New methods to assess tumor progression such as the modified Response Evaluation Criteria in Solid Tumors or European Association for the Study of Liver criteria are based on imaging to measure the vascularization and tumor volume (viable or necrotic). These however fail especially when the tumor response results in irregular development of necrotic tissue. Newer assessment techniques focus on the evaluation of tumor volume, density or perfusion. Perfusion computed tomography and Dynamic Contrast-Enhanced-UltraSound can measure the vascularization of HCC lesions and help predict tumor response to anti-angiogenic therapies. Mean Transit Time is a possible predictive biomarker to measure tumor response. Volumetric techniques are reliable, reproducible and time-efficient and can help measure minimal changes in viable tumor or necrotic tissue, allowing the prompt identification of non-responders. Volume ratio may be a reproducible biomarker for tumor response. Larger trials are needed to confirm the use of these techniques in the prediction of response to sorafenib.

Granulocytapheresis in steroid-dependent and steroid-resistant patients with inflammatory bowel disease: a prospective observational study.

BACKGROUND: Despite the mounting importance of granulocytapheresis (GCAP) for inflammatory bowel disease (IBD) treatment, its effectiveness in steroid-dependent (SD) and steroid-resistant (SR) patients has not been clearly evaluated. This prospective observational study describes the use of GCAP in SD and SR patients with either Ulcerative Colitis (UC) or Crohn's Disease (CD). METHODS: 118 patients, 83 affected by UC (55 SD and 28 SR) and 35 by CD (22 SD and 13 SR), were treated with GCAP, using Adacolumn™, for 5 consecutive weeks, 1 session/week. All patients were followed for 12 months after the end of GCAP. Clinical remission was defined as Clinical Activity Index (CAI) ≤6 for UC patients and Crohn's Disease Activity Index (CDAI) <150 for CD patients. RESULTS: All patients completed the study; no major complications were reported. At the end of GCAP 71% of UC and 63% of CD patients showed clinical remission. At 6 months the remission was maintained by 66% and 54% of UC and CD patients respectively, while at 12 months the percentages were 48% and 43%, respectively. No differences between SD and SR subgroups were reported at any timepoint. CAI and CDAI values significantly dropped after GCAP treatment and at 6 and 12 months' follow-up (p<0.05 vs baseline for both timepoints). No differences were measured in CAI and CDAI between SD and SR patients. CONCLUSION: GCAP therapy is safe and effective in inducing and maintaining clinical remission both in SD and in SR patients affected by either UC or CD.

Long-term results of sorafenib in advanced-stage hepatocellular carcinoma: what can we learn from routine clinical practice?

BACKGROUND AND AIMS: Prospective randomized trials have proven that sorafenib is a valid treatment option for patients with advanced-stage hepatocellular carcinoma (HCC). The aim of the present study is to evaluate the effectiveness and safety of sorafenib in patients encountered in routine clinical practice. METHODS: From September 2008 to March 2011, 42 cirrhotic patients (30 male; 12 female; mean age: 70.2 ± 7.6 years; range: 56-85 years) with HCC of Barcelona Clinic Liver Cancer stage B (n = 5) or C (n = 37; mean size: 66.6 ± 42.3 mm; mean number per patient: 3.3 ± 2.8) were treated with sorafenib at either a standard dose of 800 mg/day (n = 29; 69.1%) or at 400 mg/day with subsequent dose escalation (ramp-up strategy; n = 13, 30.9%). Baseline clinical parameters were comparable. Clinical data and side effects, laboratory analyses (in particular, serum α-fetoprotein) and radiological data (tumor response according to amended RECIST criteria) were assessed every 3 months. Survival was calculated by Kaplan-Meier analysis. RESULTS: Mean follow-up was 12.2 ± 9 months (range: 1-32 months). Median overall survival was 26.1 months with overall 6- and 12-month survival rates of 92.1 and 85%, respectively. Median time to radiological progression was 8 months. The progression-free rate was 64.3%. Fatigue, skin disorders and diarrhea were the most frequent grade 3-4 side effects. Treatment discontinuation occurred in 25 patients. The starting dose for the last 13 enrolled patients was 400 mg/day; in the absence of toxicity this dosage was gradually increased to 800 mg/day after 3 weeks ('ramp-up strategy'). No grade 3/4 adverse events were observed in the ramp-up group. CONCLUSION: Sorafenib is a valid treatment option for advanced-stage HCC. Starting at a lower dosage may allow prolonged compliance to treatment and might be considered according to patient tolerance.

Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study.

AIM: To assess clinical outcome of transarterial chemoembolization (TACE) in a series of patients with early-stage hepatocellular carcinoma (HCC), within Milan criteria, but clinically unfit for liver transplantation (OLT). METHODS: From January 2006 to May 2009, 67 patients (43 males, mean age 70 ± 7.6 years) with very early or early-stage unresectable HCC, within Milan selection criteria but clinically unfit for OLT, underwent TACE. The primary endpoint of the study was overall survival. Secondary endpoints were: safety, liver toxicity, 1-month tumour response according to the amended RECIST criteria, time to local and distant intrahepatic tumour recurrence and time to radiological progression. RESULTS: Two major periprocedural complications occurred (3%), consisting of liver failure. Periprocedural mortality rate was 1.5% (1 patient). A significant increase in ALT and bilirubin levels 24h after treatment was reported, with progressive decrease at discharge. At 1-month follow-up, complete and partial tumour response rates were 67.2% and 29.8%, respectively, with two cases of progressive disease. Mean follow-up was 37.3 ± 15 months. The 1-, 2-, and 3-year overall survival rates were 90.9%, 86.1%, and 80.5%, respectively. Median expected time to local tumour recurrence and intrahepatic tumour recurrence were 7.9 and 13.8 months, respectively. Radiological disease progression was observed in 12 patients (17.9%) with a mean expected time of 26.5 months. CONCLUSION: In patients with early-stage HCC, clinically excluded from OLT and unfit for surgery or percutaneous ablation, TACE is a safe and effective option, with favourable long-term survival.

Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival. RESULTS: In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival. CONCLUSIONS: Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.

Endotics system vs colonoscopy for the detection of polyps.

AIM: To compare the endotics system (ES), a set of new medical equipment for diagnostic colonoscopy, with video-colonoscopy in the detection of polyps. METHODS: Patients with clinical or familial risk of colonic polyps/carcinomas were eligible for this study. After a standard colonic cleaning, detection of polyps by the ES and by video-colonoscopy was performed in each patient on the same day. In each single patient, the assessment of the presence of polyps was performed by two independent endoscopists, who were randomly assigned to evaluate, in a blind fashion, the presence of polyps either by ES or by standard colonoscopy. The frequency of successful procedures (i.e. reaching to the cecum), the time for endoscopy, and the need for sedation were recorded. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ES were also calculated. RESULTS: A total of 71 patients (40 men, mean age 51.9 ± 12.0 years) were enrolled. The cecum was reached in 81.6% of ES examinations and in 94.3% of colonoscopies (P = 0.03). The average time of endoscopy was 45.1 ± 18.5 and 23.7 ± 7.2 min for the ES and traditional colonoscopy, respectively (P < 0.0001). No patient required sedation during ES examination, compared with 19.7% of patients undergoing colonoscopy (P < 0.0001). The sensitivity and specificity of ES for detecting polyps were 93.3% (95% CI: 68-98) and 100% (95% CI: 76.8-100), respectively. PPV was 100% (95% CI: 76.8-100) and NPV was 97.7% (95% CI: 88-99.9). CONCLUSION: The ES allows the visualization of the entire colonic mucosa in most patients, with good sensitivity/specificity for the detection of lesions and without requiring sedation.

The intelligent, painless, "germ-free" colonoscopy: A Columbus' egg for increasing population adherence to colorectal cancer screening?

Colorectal cancer (CRC) represents a major cause of morbidity and mortality. Although it is widely accepted that CRC screening in average risk populations lowers CRC incidence and mortality, a disappointedly low adherence rate to both faecal occult blood testing and colonoscopy-based screening programs has been observed in Italy and in other European countries. Main reasons for the low acceptance of colonoscopy-based CRC screening has been ascribed to lack of recommendations given by general practitioners, fear of discomfort or complications, embarrassment, and avoidance of unpleasant preparation. New advances in endoscopic technology such as colon capsule and robotic colonoscopy might represent the ideal tool for CRC screening since they reduce or eliminate procedure-related pain and discomfort. Moreover, no disinfection between procedures is required. Motion of the new probes along the gastrointestinal tract is achieved either in passive modality by utilizing the gut peristalsis (colon capsule) or in active "intelligent" modality by means of computer-assisted propulsion (robotic colonoscopy). In this review, the preliminary clinical results obtained with the new devices are summarized. It is expected that the new instruments will be soon available in clinical practice with the hope of increasing adherence to CRC screening programs.

Functional evaluation of the endotics system, a new disposable self-propelled robotic colonoscope: in vitro tests and clinical trial.

OBJECTIVE: Currently, the best method for CRC screening is colonoscopy, which ideally (where possible) is performed under partial or deep sedation. This study aims to evaluate the efficacy of the Endotics System, a new robotic device composed of a workstation and a disposable probe, in performing accurate and well-tolerated colonoscopies. This new system could also be considered a precursor of other innovating vectors for atraumatic locomotion through natural orifices such as the bowel. The flexible probe adapts its shape to the complex contours of the colon, thereby exerting low strenuous forces during its movement. These novel characteristics allow for a painless and safe colonoscopy, thus eliminating all major associated risks such as infection, cardiopulmonary complications and colon perforation. METHODS: An experimental study was devised to investigate stress pattern differences between traditional and robotic colonoscopy, in which 40 enrolled patients underwent both robotic and standard colonoscopy within the same day. RESULTS: The stress pattern related to robotic colonoscopy was 90% lower than that of standard colonoscopy. Additionally, the robotic colonoscopy demonstrated a higher diagnostic accuracy, since, due to the lower insufflation rate, it was able to visualize small polyps and angiodysplasias not seen during the standard colonoscopy. All patients rated the robotic colonoscopy as virtually painless compared to the standard colonoscopy, ranking pain and discomfort as 0.9 and 1.1 respectively, on a scale of O to 10, versus 6.9 and 6.8 respectively for the standard device. CONCLUSIONS: The new Endotics System demonstrates efficacy in the diagnosis of colonic pathologies using a procedure nearly completely devoid of pain. Therefore, this system can also be looked upon as the first step toward developing and implementing colonoscopy with atraumatic locomotion through the bowel while maintaining a high level of diagnostic accuracy;

Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: a cohort study.

AIM: To prospectively evaluate the short and long term clinical impact of selective transarterial chemoembolization (TACE) on liver function in patients with hepatocellular carcinoma (HCC). To assess side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. METHODS: One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine-aminotransferase (ALT), prothrombin time (PT) and bilirubin. According to Cancer Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC) staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed "on demand". Liver function tests were checked in all patients every four months. RESULTS: After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 +/- 1.12 to 6.11 +/- 1.57 at discharge time (P < 0.0001), decreasing after four months to 5.81 +/- 0.73 (not significant). ALT, PT and bilirubin significantly (P < 0.0001) increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 +/- 6.3 mo (median: 16 mo). Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. CONCLUSION: Selective TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.

The role of video capsule endoscopy for evaluating obscure gastrointestinal bleeding: usefulness of early use.

BACKGROUND: We report our preliminary experience with the use of video capsule endoscopy (VCE) in 64 patients with obscure gastrointestinal bleeding (OGIB) and suspected small intestine disease. METHODS: To be eligible for VCE, patients had to have undergone upper endoscopy, small bowel series, and colonscopy without discovering any source of bleeding. To find the best timing to perform VCE, the patients were retrospectively divided in two groups of 32 cases each: group 1 with patients who had been submitted to VCE within 15 days from OGIB diagnosis, and group 2 with patients who had been submitted to VCE at least 15 days after OGIB diagnosis. RESULTS: Lesions were found by VCE in 29 (91%) in group 1: angioectasia-like lesions of the small bowel in 12, some erosions of the ileum without signs of bleeding in 14, a polyp with erosions in 1, and a bleeding site where the surgery showed a tumor of the ileum in 2 patients. In 2 cases, VCE missed showing two small tumors that were revealed by laparoscopy in 1 case and by push enteroscopy in the other. In group 2, lesions were found by VCE in 11 (34%): angioectasia-like lesions of the small bowel in 6, some erosions in 3, a short segmental stenosis in 1, and two polyps in 1. In 1 case, VCE missed showing a small polyp in the jejunum that was revealed by push enteroscopy. In none of these cases was a bleeding site identified. VCE was well tolerated and able to acquire good images in patients with OGIB. It showed lesions in 91% of the patients in group 1 and 34% of cases in group 2. CONCLUSIONS: Our data suggest that the optimal timing to perform VCE is within a few days after the occurrence of bleeding, possibly within 2 weeks.