Anastomotic leaks after anterior resection for mid and low rectal cancer: survey of the Italian Society of Colorectal Surgery

BACKGROUND: The aim of the survey was to assess the incidence of anastomotic leaks (AL) and to identify risk factors predicting incidence and gravity of AL after low anterior resection (LAR) for rectal cancer performed by colorectal surgeons of the Italian Society of Colorectal Surgery (SICCR). METHODS: Information about patients with rectal cancers less than 12 cm from the anal verge who underwent LAR during 2005 was collected retrospectively. AL was classified as grade I to IV according to gravity. Fifteen clinical variables were examined by univariate and multivariate analyses. Further analysis was conducted on patients with AL to identify factors correlated with gravity. RESULTS: There were 520 patients representing 64% of LAR for rectal cancer performed by SICCR members. The overall rate of AL was 15.2%. Mortality was 2.7% including 0.6% from AL. The incidence of AL was correlated with higher age (p<0.05), lower (<20 per year) centre case volume (p<0.05), obesity (p<0.05), malnutrition (p<0.01) and intraoperative contamination (p<0.05), and was lower in patients with a colonic J-pouch reservoir (p<0.05). In the multivariate analysis age, malnutrition and intraoperative contamination were independent predictors. The only predictor of severe (grade III/IV) AL was alcohol/smoking habits (p<0.05) while the absence of a diverting stoma was borderline significant (p<0.07). CONCLUSION: Our retrospective survey identified several risk factors for AL. This survey was a necessary step to construct prospective interventional studies and to establish benchmark standards for outcome studies.     

The limits of evidence-based medicine.

The importance of clinical research for the practice of clinical medicine is immense and undeniable. Yet the type of knowledge gained from clinical research, referred to here as "empirical evidence," is itself insufficient to provide for optimal clinical care. A gap exists between empirical evidence and clinical practice. Proponents of evidence-based medicine have clearly acknowledged one aspect of this gap: the part that requires the consideration of values, both patient and professional, prior to arriving at medical decisions. Not as clearly recognized, however, is the gap that exists due to the fact that empirical evidence is not directly applicable to individual patients, as the knowledge gained from clinical research does not directly answer the primary clinical question of what is best for the patient at hand. Proponents of evidence-based medicine have made a conceptual error by grouping knowledge derived from clinical experience and physiologic rationale under the heading of "evidence" and then have compounded the error by developing hierarchies of "evidence" that relegate these forms of medical knowledge to the lowest rungs. Empirical evidence, when it exists, is viewed as the "best" evidence on which to make a clinical decision, superseding clinical experience and physiologic rationale. But these latter forms of medical knowledge differ in kind, not degree, from empirical evidence and do not belong on a graded hierarchy. As they differ in kind, these other forms of medical knowledge can be viewed as complementary to empirical evidence and their incorporation necessary to overcome the intrinsic gap noted above. Clinicians, then, need to incorporate knowledge from 5 distinct areas into each medical decision: (1) empirical evidence, (2) experiential evidence, (3) physiologic principles, (4) patient and professional values, and (5) system features. The relative weight given to each of these areas is not predetermined, but varies from case to case.     

Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience

Multiple endocrine neoplasia type 1 (MEN1) gastro-entero-pancreatic (GEP) tumours develop from the pancreatic islets and from the endocrine cells of the duodenal and gastric mucosa. Even if GEP tumours have generally a benign course, a subgroup of them shows an aggressive behaviour and is a major cause of death amongst MEN1 patients. Diagnosis of insulinoma should lead promptly to pancreatic surgery. MEN1 gastrinomas are multiple and almost exclusively localized in the duodenum. Cure rate for Zollinger-Ellison syndrome in MEN1 is low when surgery is limited to tumour enucleation or full thickness duodenal wall resection. Conversely, pancreatoduodenectomy is followed by higher chance of cure. For nonfunctioning tumours exceeding 1 cm diameter in size a prompt treatment is recommended due to their high malignant potential. Gastroscopic surveillance is indicated for the frequent occurrence of multiple, small, type 2 fundic carcinoids. Endoscopic removal is possible for lesions growing in the mucosa-submucosa, but partial or even total gastrectomy is recommended for the small number of gastric carcinoids infiltrating the muscular layers.     

Left ventricular aneurysm repair: early survival.

BACKGROUND: The aim of this study was to evaluate the early survival in patients submitted to left ventricular (LV) repair and concomitant myocardial revascularization. METHODS: We retrospectively reviewed the records of 51 patients who were submitted to LV repair and concomitant myocardial revascularization between January 1998 and June 2003. Of 51 patients (44 males with a mean age of 60+/-9.2 years, and 7 females with a mean age of 61+/-6.5 years), 29 (56.9 %) were submitted to the McCarthy technique, 16 (31.3 %) to the technique that was described by Jatene and modified by Dor, and 6 (11.8%) to the Cooley technique (linear repair). The mean preoperative LV ejection fraction was 36.5+/-7.7 %, the mean preoperative LV end-diastolic diameter was 61.8+/-3.9 mm, the mean preoperative LV end-systolic diameter was 49.9+/-5.1 mm, the mean preoperative interventricular septal thickness was 9.7+/-1.7 mm, and finally, the mean posterior wall thickness was 8.9+/-1 mm. The mean follow-up was 30.7+/-23.4 months (range 11-82 months). RESULTS: One patient died during surgery (1.9%) and one early postoperatively (1.9%). The causes of death were respectively irreversible ventricular fibrillation and low cardiac output syndrome. The overall survival at follow-up was 98% (49 patients). One patient died during follow-up of myocardial infarction. At follow-up, all patients presented with improved clinical symptoms, and had a better mean NYHA functional class with respect to the preoperative value (3.3+/-0.3 vs 2.0+/-0.5, p < 0.05). Besides, the mean CCS angina class decreased in all patients (3.4+/-0.2 vs 1.9+/-0.3, p < 0.05). The average LV ejection fraction increased from 36.3+/-7.7 to 44.3+/-4.9% (p < 0.001), the average LV end-diastolic diameter decreased from 61.7+/-3.9 to 55.5+/-5.6 mm (p < 0.001), and the average LV end-systolic diameter decreased from 49.9+/-5.1 to 40.4+/-5.1 mm (p < 0.001). No statistically significant difference was found between the preoperative and postoperative data regarding the interventricular septal thickness (9.7+/-1.7 vs 10.3+/-1.6 mm, p = NS), and the posterior wall thickness (9.7+/-1 vs 8.8+/-1.3 mm, p = NS). CONCLUSIONS: LV aneurysm repair and concomitant myocardial revascularization may be performed with an acceptable surgical risk and a good early survival.     

Mutations of the APC gene in human sporadic colorectal cancers

BACKGROUND: Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis. METHODS: Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region. RESULTS: Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C). Conclusions: These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.     

Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients

PURPOSE: Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE.SUBJECTS AND METHODS: We examined 110 consecutive patients with suspected PE. The study protocol included assessment of clinical probability, echocardiography, and perfusion lung scanning. Pulmonary angiography was performed in all patients with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used the presence of any two of the following: right ventricular (RV) hypokinesis, RV end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest probabilities in calculating, after echocardiography, the posttest probabilities of PE.RESULTS: Pulmonary angiography confirmed PE in 43 (39%) of 110 patients. Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and 98%, respectively. The posttest probabilities of PE conditioned by a negative echocardiogram were 5%, 33%, and 81%, respectively.CONCLUSIONS: In unselected patients with suspected PE, transthoracic echocardiography fails to identify some 50% of patients with angiographically proven PE. Although echocardiographic findings of RV strain, paired with a high clinical likelihood, support a diagnosis of PE, the transthoracic echocardiography has to have a better sensitivity to be used as a screening test to rule out PE.     

Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations

OBJECTIVE: To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha (TNFalpha) monoclonal antibody (infliximab) in the treatment of spondyloarthropathy (SpA) associated with active and inactive Crohn's disease (CD). METHODS: Twenty four patients with SpA associated with active or inactive CD (16 active, 8 quiescent) were treated with anti-TNFalpha monoclonal antibody (infliximab) with repeated infusions for a period of 12-18 months. The treatment aimed at ameliorating the general musculoskeletal and spinal pain, controlling peripheral arthritis and enthesitis, decreasing the BASDAI score, modifying acute phase reactants, and reducing CD activity. RESULTS: Infliximab improved both gastrointestinal (p<0.01) and overall articular symptoms (BASDAI, p<0.01; general musculoskeletal and spinal pain, p<0.01; peripheral arthritis, p<0.01) in patients with active CD. Additionally, infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis (p<0.01) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers. Amelioration of gut and musculoskeletal involvement persisted for up to 12 months. CONCLUSION: Infliximab may act on the inflammation of entheses and of periarticular structures, which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA, suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD.     

Microsatellite instability in a population of sporadic colorectal cancers correlation between genetic and pathological profiles

BACKGROUND: Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear. AIMS: To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours. METHODS: Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed. RESULTS: High frequency microsatellite instability and low-frequency microsatellite instability and apparently stable cancers were different in terms of tumour localisation (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's-like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's-like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite instability tumours were preferentially located in the right colon and exhibited a higher frequency of loss of heterozygosity at the FHIT locus compared with low-frequency microsatellite instability and apparently stable cases (p=0.0243). Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer growth (p=0.0374), were the only factors affecting patient survival. However, a borderline improvement was noted in overall survival in high-frequency microsatellite instability and low-frequency microsatellite instability cancer patients (p=0.062). CONCLUSIONS: These results indicate that low-frequency microsatellite instability tumours have different genetics and histological features and suggest that they are a distinct group of colorectal cancers.     

Short-term effect of the addition of leukotriene receptor antagonists to the current therapy in severe asthmatics

In a single blind study, the short-term efficacy of the addition of leukotriene receptor antagonists (LTRA: montelukast 10 mg o.d. in 15 subjects, zafirlukast 20 mg b.i.d. in 11 subjects) to the current therapy was evaluated in severe asthmatics, unstable under regular treatment with high dose inhaled corticosteroids, bronchodilators and, in seven of them, oral corticosteroids. Each subject monitored symptoms, PEF and rescue medication during two weeks with the addition of placebo, and during two following weeks with the addition of LTRA; clinic FEV1 was measured at the beginning and at the end of each 2 weeks period. There was no significant difference in the mean FEV1, PEF, symptom score and rescue medication use between two periods of placebo and LTRA treatments. When two subjects with asthma exacerbation during treatment with LTRA were excluded, FEV1 was higher after LTRA than after placebo treatment (p=0.055). An increase in FEV1>12% pred. at the end of LTRA treatment was observed in five out of 26 subjects (19%). We suggest that LTRA have no overall significant efficacy in severe asthmatics not controlled by high dose inhaled corticosteroids and bronchodilators, but that a minority of these patients could be particularly sensitive to the positive effects of these drugs. The detection of these 'responders' could be relevant in the treatment of severe asthma.