Sebastiano Biondo

Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data

BACKGROUND Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. METHODS In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. FINDINGS 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors. INTERPRETATION Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. FUNDING None.

Large Bowel Obstruction: Predictive Factors for Postoperative Mortality

PURPOSEThe aims of this study were to assess the prognostic value for mortality of several factors in patients with colonic obstruction and to study the differences between proximal and distal obstruction.METHODSTwo-hundred and thirty-four consecutive patients who underwent emergency surgery for colonic obstruction were studied. Patients with an obstructive lesion distal to the splenic flexure were assessed as having a distal colonic obstruction. Resection and primary anastomosis was the operation of choice in selected patients. Alternative procedures were Hartmann’s procedure in high-risk patients, subtotal colectomy in cases of associated proximal colonic damage, and colostomy or intestinal bypass in the presence of irresectable lesions. Obstruction was considered proximal when the tumor was situated at the splenic flexure or proximally and a right or extended right colectomy was performed. A range of factors were investigated to estimate the probability of death: gender, age, American Society of Anesthesiologists score, nature of obstruction (benign vs. malign), location of the lesion (proximal vs. distal), associated proximal colonic damage and/or peritonitis, preoperative transfusion, preoperative renal failure, and laboratory data (hematocrit ≤30 percent, hemoglobin ≤10 g/dl, and leukocyte count >15,000/mm3). Univariate and multivariate forward steptwise logistic regression analysis was used to study the prognostic value of each significant variable in terms of mortality.RESULTSOne or more complications were detected in 109 patients (46.5 percent). Death occurred in 44 patients (18.8 percent). No differences were observed between proximal and distal obstruction. Age (>70 years), American Society of Anesthesiologists III–IV score, preoperative renal failure, and the presence of proximal colon damage with or without peritonitis were significantly associated with postoperative mortality in the univariate analysis. Only American Society of Anesthesiologists score, presence of proximal colon damage, and preoperative renal failure were significant predictors of outcome in multivariate logistic regression.CONCLUSIONLarge bowel obstruction still has a high of mortality rate. An accurate preoperative evaluation of severity factors might allow stratification of patients in terms of their mortality risk and help in the decision-making process for treatment. Such an evaluation would also enable better comparison between studies performed by different authors. Principles and stratification similar to those of distal lesions should be considered in patients with proximal colonic obstruction.

Prognostic factors for mortality in Left colonic peritonitis : A new scoring system

BACKGROUND Perforating lesions of the colon affect a heterogeneous group of patients, often elderly, and usually present as abdominal emergencies, with high morbidity and mortality. The aims of this study were to assess the prognostic value of specific factors in patients with left colonic peritonitis and to evaluate the utility of a scoring method that allows one to define groups of patients with different mortality risks. STUDY DESIGN Between January 1994 and December 1999, 156 patients (77 men and 79 women), with a mean (SD) age of 63.2 years (15.5 years) (range 22 to 87 years), underwent emergency operation for a distal colonic perforation. Intraoperative colonic lavage was the first choice operation and it was performed in 74 patients (47.4%). There were three alternative procedures: the Hartmann operation was performed in 69 patients (44.2%), subtotal colectomy in 9, and colostomy in 4 patients. We analyzed specific variables for their possible relation to death including gender, age, American Society of Anesthesiologists (ASA) score, immunocompromised status, etiology, and degree of peritonitis, preoperative organ failure, time (hours) between hospital admission and surgical intervention, and degree of temperature elevation (38 degrees C). Univariate relations between predictors and outcomes (death) were analyzed using logistic regression. Multivariate logistic regression analysis was used to assess the prognostic value of combinations of the variables. Significant factors identified in univariate and multivariate logistic regression analyses were used to define a left colonic Peritonitis Severity Score (PSS). Factors that were significant only in univariate analysis scored 2 points if present and 1 if not. Variables significant in multivariate analysis were scored from 1 to 3 points. Patients were randomly split into two groups, one to calculate the scoring system and the other to validate it. RESULTS Overall postoperative mortality rate was 22.4%. Septic-related mortality was observed in 24 patients (15.4%). Age, peritonitis grade, ASA score, immunocompromised status, and ischemic colitis were significant for postoperative death in univariate analysis. But only ASA score and preoperative organ failure were significantly associated with postoperative mortality in multivariate logistic regression analysis. The PSS, as defined in this study, was related to outcomes of patients. Mortality rate increased from 0%, when PSS was 6 points (minimum possible score), to 100% in patients with a PSS of 13 (maximum possible PSS = 14). CONCLUSIONS Left colonic peritonitis continues to have a persistently high mortality in patients with septic complications. ASA score and preoperative organ failure are the only factors that are significantly associated with mortality in the multivariate analysis. The PSS classification may help uniformly define the mortality risk of patients with distal large bowel peritonitis, and may help to increase the comparability of studies carried out at different centers.

Randomized clinical study of Gastrografin administration in patients with adhesive small bowel obstruction.

Oral Gastrografin® has been used to differentiate partial from complete small bowel obstruction (SBO). It may have a therapeutic effect and predict the need for early surgery in adhesive SBO. The aim of this study was to determine whether contrast examination in the management of SBO allows an early oral intake and reduces hospital stay.

Low anterior resection syndrome and quality of life: an international multicenter study.

BACKGROUND: An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to 90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome. OBJECTIVE: The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer. DESIGN: The study was designed as an international cross-sectional study involving 5 centers in 4 European countries. PATIENTS: All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery. INTERVENTIONS: The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30. MAIN OUTCOME MEASURES: Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea. RESULTS: A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation. LIMITATIONS: The cross-sectional design prevents an evaluation of causality. CONCLUSIONS: The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.

Outpatient Versus Hospitalization Management for Uncomplicated Diverticulitis A Prospective, Multicenter Randomized Clinical Trial (DIVER Trial)

Objective:We compare the results of 2 different strategies for the management of patients with uncomplicated left colonic diverticulitis and to analyze differences in quality of life and economic costs. Background:The most frequent standard management of acute uncomplicated diverticulitis still is hospital admission both in Europe and United States. Methods:This multicenter, randomized controlled trial included patients older than 18 years with acute uncomplicated diverticulitis. All the patients underwent abdominal computed tomography. There were 2 strategies of management: hospitalization (group 1) and outpatient (group 2). The first dose of antibiotic was given intravenously to all patients in the emergency department and then group 1 patients were hospitalized whereas patients in group 2 were discharged. The primary end point was the treatment failure rate of the outpatient protocol and need for hospital admission. The secondary end points included quality-of-life assessment and evaluation of costs. Results:A total of 132 patients were randomized: 4 patients in group 1 and 3 patients in group 2 presented treatment failure without differences between the groups (P = 0.619). The overall health care cost per episode was 3 times lower in group 2, with savings of &OV0556;1124.70 per patient. No differences were observed between the groups in terms of quality of life. Conclusions:Outpatient treatment is safe and effective in selected patients with uncomplicated acute diverticulitis. Outpatient treatment allows important costs saving to the health systems without negative influence on the quality of life of patients with uncomplicated diverticulitis. Trial registration ID: EudraCT number 2008-008452-17.

Surgical Site Infection in Elective Operations for Colorectal Cancer After the Application of Preventive Measures

OBJECTIVES To assess the prevalence of surgical site infection (SSI) after elective operations for colon and rectal cancer after the application of evidence-based preventive measures and to identify risk factors for SSI. DESIGN Prospective, observational, multicenter. SETTING Tertiary and community public hospitals in Catalonia, Spain. PATIENTS Consecutive patients undergoing elective surgical resections for colon and rectal cancer during a 9-month period. MAIN OUTCOME MEASURES The prevalence of SSI within 30 days after the operations and risk factors for SSI. RESULTS Data from 611 patients were documented: 383 patients underwent operations for colon cancer and 228 underwent operations for rectal cancer. Surgical site infection was observed in 89 (23.2%) colon cancer patients (superficial, 12.8%; deep, 2.1%; and organ/space, 8.4%) and in 63 (27.6%) rectal cancer patients (superficial, 13.6%; deep, 5.7%; and organ/space, 8.3%). For colon procedures, the following independent predictive factors were identified: for incisional SSI, open procedure vs laparoscopy; for organ/space SSI, hyperglycemia at 48 hours postoperatively (serum glucose level, >200 mg/dL), ostomy, and National Nosocomial Infection System index of 1 or more. In rectal procedures, no risk factors were identified for incisional SSI; hyperglycemia at 48 hours postoperatively (serum glucose level, >200 mg/dL) and temperature lower than 36°C at the time of surgical incision were associated with organ/space SSI. CONCLUSION The prevalence of SSI in elective colon and rectal operations remains high despite the application of evidence-based preventive measures.

Anastomotic Dehiscence After Resection and Primary Anastomosis in Left-Sided Colonic Emergencies

PURPOSEThere is no consensus about the risk factors for anastomotic failure after elective or emergency colorectal surgery. The purpose of this study was to analyze the factors that may contribute in anastomotic dehiscence.METHODSA total of 208 patients who underwent left colonic resection and primary anastomosis for distal colonic emergencies were studied. Preoperative and operative variables analyzed for each patient were gender, age, American Society of Anesthesiologists score, comorbidities, indication for surgery, etiology of the disease, presence and grade of peritonitis, preoperative creatinine, hematocrit, hemoglobin, and leukocyte count, need for preoperative and operative transfusion. The end point was the clinical evident incidence of anastomotic leak. Bivariate comparisons of those patients with or without anastomotic leak were unpaired, and all tests of significance were two-tailed. A multivariate analysis, in which presentation of anastomotic leak was the dependent outcome variable, was performed by forward stepwise logistic regression model.RESULTSOne hundred five patients (50.4 percent) had one or more complications. Anastomotic leak was diagnosed in 12 patients (5.7 percent). Seventeen patients (8.2 percent) needed a reoperation for complication. The overall mortality was 6.2 percent (13 patients). Obesity was significant as a predictor of anastomotic leak.CONCLUSIONSObesity is a factor predicting anastomotic leak risk after resection and primary anastomosis for left-sided colonic emergencies.

International Validation of the Low Anterior Resection Syndrome Score

Objective:The aims of this study were to investigate the convergent and discriminative validity and reliability of the low anterior resection syndrome (LARS) score in an international setting. Background:The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal cancer surgery. The score is intended to be commonly used in international research and clinical practice in the future. Therefore, a thorough validation in an international setting is of utmost importance. Methods:The LARS score was translated using methods in keeping with current international recommendations. A total of 801 patients operated for rectal cancer in Sweden, Spain, Germany, and Denmark completed the LARS score questionnaire, including an anchor question assessing the impact of bowel function on quality of life. A subgroup of 218 patients completed the LARS score twice. Data were analyzed per country. Results:The LARS score has demonstrated a high convergent validity in terms of a high correlation between LARS score and quality of life (P < 0.001). Sensitivity ranged from 67.7% to 88.3% and specificity from 58.1% to 86.3%. The LARS score was able to discriminate between groups of patients differing with regard to radiotherapy, surgery, and age (P < 0.05). The score also demonstrated high reliability at test-retest with narrow limits of agreement and no statistically significant difference between scores at the first and second test. Conclusions:The Swedish, Spanish, German, and Danish versions of the LARS score have proven to be valid and reliable tools for measuring LARS in European rectal cancer patients.

DNA Methylation Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer (CRC) and precursor lesions have been extensively studied. Different panels have been reported attempting to improve current protocols in clinical practice, although no definite biomarkers have been established. In the present study, we have examined patient biopsies starting from a comprehensive analysis of DNA methylation differences between paired normal and tumor samples in known cancer-related genes aiming to select the best performing candidates informative for CRC diagnosis in stool samples. Five selected markers were considered for subsequent analyses in independent biologic cohorts and in silico data sets. Among the five selected genes, three of them (AGTR1, WNT2 and SLIT2) were validated in stool DNA of affected patients with a detection sensitivity of 78% [95% confidence interval (CI), 56%–89%]. As a reference, DNA methylation of VIM and SEPT9 was evaluated in a subset of stool samples yielding sensitivities of 55% and 20%, respectively. Moreover, our panel may complement histologic and endoscopic diagnosis of inflammatory bowel disease (IBD)-associated neoplasia, as it was also efficient detecting aberrant DNA methylation in non-neoplastic tissue samples from affected patients. This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA and may help in the follow-up of high-risk patients with IBD. Cancer Prev Res; 6(7); 656–65. ©2013 AACR.