Marcello Ingrosso

A new regimen of bowel preparation for PillCam colon capsule endoscopy: a pilot study.

BACKGROUND Colon capsule endoscopy (CCE) represents a new diagnostic, endoscopic technology for colonic exploration. Current protocols of preparation led to discordant rates of adequate cleansing level or CCE excretion. AIM To evaluate the effect of a new regimen of bowel preparation for CCE on colon cleansing levels and on rate of capsule excretion. STUDY 60 patients were prospectively enrolled. The new regimen of preparation consisted of a split regimen of PEG administration and of a 45 mL dose of sodium phosphate (NaP). Four senna tablets and a low-residue diet were also included. CCE excretion rate, colon cleansing, and accuracy were assessed. RESULTS Forty-six patients were included in the final analysis, 13 patients (22%) being excluded because of preparation protocol deviations and one due to CCE technical failure (2%). At CCE, bowel preparation was rated as good in 78% of patients, fair in 20% and poor in 2%. CCE excretion rate occurred in 83% of patients. CCE sensitivity and specificity for significant findings was 100% and 95%, respectively. CONCLUSIONS The combination of a split-dose of PEG solution with a low dose of NaP boosters resulted in high rates of adequate cleansing level and CCE excretion.

Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate cancer treated with radiotherapy.

PURPOSE To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. METHODS AND MATERIALS Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. RESULTS After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥ 2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥ 2 clinical rectal late toxicity was higher in patients with grade ≥ 2 (32% vs. 15 %, p = 0.02) or grade ≥ 3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥ 2 (31% vs. 16 %, p = 0.04) or ≥ 3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. CONCLUSIONS Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

Neoadjuvant Accelerated Concomitant Boost Radiotherapy and Multidrug Chemotherapy in Locally Advanced Rectal Cancer: A Dose-Escalation Study

ObjectivesTo determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients. MethodsPatients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria. ResultsForty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level. ConclusionsAn intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.

Early radiation-induced mucosal changes evaluated by proctoscopy: Predictive role of dosimetric parameters

BACKGROUND AND PURPOSE Late rectal complications are assessed according to different scoring systems. Endoscopy can provide a more sensitive estimation of early radiation damage. The aim of this paper is to investigate the correlation between dosimetric parameters and rectal mucosal changes after radiotherapy (RT). MATERIALS AND METHODS Patients with prostate adenocarcinoma treated with curative or adjuvant RT underwent endoscopy 1 year after RT. Receiver operating characteristics (ROC) analysis was performed to analyze the predictive capability of the dosimetric variables in determining mucosal changes classified by Vienna Rectoscopy Score (VRS). RESULTS The best dosimetric predictors of grade ≥2 telangiectasia were rectal (r) V(60 Gy) (p=0.014), rV(70 Gy) (p=0.017) and rD(mean) (p=0.018). Similar results were obtained for grade ≥2 VRS. The set of rV(60 Gy)<34.4%, rV(70 Gy)<16.7% and rD(mean)<57.5 Gy was associated with a decreased risk of grade ≥2 telangiectasia and VRS. CONCLUSIONS rV(60 Gy), rV(70 Gy) and rD(mean) were the strongest predictors of rectal mucosal alterations. In-depth analysis is required to correlate each mucosal alteration with late rectal toxicity in order to suggest early proctoscopy as surrogate end-point for rectal late toxicity in studies aimed at reducing this important complication.

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study

Abstract The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. Material and methods. Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m 2. Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. Results and discussion. Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m 2) in patients with resected pancreatic carcinoma.

Predictive factors of late-onset rectal mucosal changes after radiotherapy of prostate cancer

BACKGROUND/AIM The Vienna Rectoscopy Score (VRS; from 0, absence of rectal mucosal changes, to 5) assessed 1 year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS. PATIENTS AND METHODS We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with definitive or postoperative radiotherapy (RT) underwent endoscopy 1 year after RT. Relationships between VRS of 2 or more and treatment parameters were investigated by univariate and multivariate logistic analyses. RESULTS One hundred and ninety-five patients (mean age=69 years; range=43-81 years) were considered eligible for the study. At univariate analysis, patients treated with hypofractionation plus radiosurgery boost (p<0.001) and an equivalent dose in 2 Gy per fraction (EQD2) (α/β=3) ≥75 Gy (p<0.001) was associated with a significantly higher incidence of VRS ≥2 after 1 year of follow-up. At multivariate analysis, radiosurgery boost was an independent risk factor for developing rectal mucosal lesions (VRS ≥2), yielding an odds ratio (OR) of 4.14 (95% confidence interval (CI)=1.2-13.8), while pelvic surgery was inversely associated with VRS ≥2 (OR=0.39; 95% CI=0.17-0.94). CONCLUSION Hypofractionation followed by radiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventative treatment strategies are needed when using radiosurgery boost after hypofractionated RT.

Diffuse intestinal pneumatosis after an Endoscopic Retrograde Cholangiopancreatography: A paradigmatic case for an old pathogenetic dilemma

[1] Sezgin O, Tezel A, Sahin B. Limited duodenal pneumatosis during needle-knife sphincterotomy. Endoscopy 1999;31:S54. An 83 year-old man with severe jaundice due to an advanced ancreatic adenocarcinoma was referred to our hospital to undergo ndoscopic Retrograde Cholangiopancreatography (ERCP). In his ast history a chronic bronco-pulmonary obstructive disease COPD) was present. At admission he was in poor general condition resenting signs of malnutrition (albumin 1.8 g/dl). Before ERCP the atient experienced transient hypotension requiring colloid infuion and etilefrine chloride administration. Sphincterotomy and tent placement allowed biliary drainage. Few hours after ERCP he patient complained of abdominal pain, vomiting and hypotenion. Duodenal perforation was suspected and a CT-scan showed a iffuse intestinal pneumatosis (IP) from the esophagus to the jejual walls (Fig. 1) associated with severe gastric dilation. Gastric ecompression, antibiotics and 48-hours of bowel rest led to partial ymptoms relief. After 24 hours a CT-scan showed complete IP reslution (Fig. 2) but progressive renal failure occurred. The patient ied for the consequences of multi-organ failure.