Patient management after primary rectal cancer diagnosis. Special focus on surgical treatment for non-metastatic disease.

Background: Rectal cancer is a public health priority. Primary objectives of this study were to evaluate the quality of care for non-metastatic rectal cancer using process and outcome indicators. Delay of management, length of stay and readmission rate, sphincter preservation, morbidity, number of examined lymph nodes, mortality, overall and disease-free survivals were evaluated. Secondary objectives were to estimate the relationship between possible predictive parameters for (1) anastomotic leakage (logistic regression), (2) overall or disease-free survivals (cox regression).Methods: We performed a retrospective study on 312 consecutive patients diagnosed with primary rectal cancer between 2016 and 2019. We focused on the 163 patients treated by surgery for non-metastatic cancer.Results: The treatment began within 33 days (range 0-264) after incidence, resection rate was 67%. Digestive continuity rate in lower, middle and upper rectum was 30%, 87% and 96%. Median of 14 lymph nodes (range 1-46) was analyzed. Length of stay and readmission rate were 11 days (range 3-56) and 4%, respectively. Within 90 postoperative days, clinical anastomotic leakage occurred in 9.2% of cases, major morbidity rate was 17%, mortality 1.2%. Multivariate analysis revealed that stoma decreased the risk of anastomotic leakage [hazard ratio: 0.16; 95% confidence intervals: 0.04-0.63; p = 0.008]. The 5-year overall survival after surgery was 85 ± 4%, disease-free survival 83 ± 4%. Patients with major complications, male gender and R1/R2 resection margin had a poorer prognosis.Conclusion: This work showed encouraging results in rectal cancer treatment in our institution, our results were in line with recommendations at the time.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years.

PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.

[In vivo studies of the inhbitory effect of various food components on aflatoxin B1 metabolism]. / Etude in vivo de l'effet inhibiteur de certains composants alimentaires sur la métabolisation de l'aflatoxine B1.

Possible interferences with aflatoxin B1 metabolism, of some compounds naturally present in food (quercetin, beta-naphthoflavone), resulting from way of cooking method (2-aminodipyrido [1,2-a; 1',2'-d] imidazole (Glu-P-2), norharmane; NH) or used as food additives (butylated hydroxytoluene; BHT) have been studied in vivo by evaluating the production of adducts to glutathione and adducts to serum proteins in laboratory rats. Glu-P-2 and norharmane inhibit strongly the production of adducts to glutathione whereas quercetin and beta-naphthoflavone have only a low effect. BHT is completely ineffective. The adducts to proteins are inhibited by the five compounds, norharmane being the most efficient.

[In vitro study of the interference of certain food components with the metabolism of aflatoxin B1]. / Etude in vitro de l'interférence de certains constituants alimentaires avec la métabolisation de l'aflatoxine B1.

Some compounds naturally present in food (quercetin, beta-naphthoflavone), used as food additives (butylated hydroxytoluene, sodium sulfite) or resulting from the way they were cooked (2-aminodipyrido [1,2-a; 3', 2'-d] imidazole, norharmane) can interfere with AFB1 metabolism. These interferences have been studied in vitro by evaluating the production of adducts to glutathione and by the Ames test on Salmonella typhimurium. Whereas all compounds produced a drastic decrease of the mutagenic activity, the first three only (quercetin, beta-naphthoflavone, butylated hydroxytoluene) interfered with the production of the adducts to glutathione.

Primary balloon dilatation in coarctation of the aorta complicated by severe aortic insufficiency.

The combination of coarctation of the aorta in the presence of severe aortic insufficiency poses a serious clinical problem. Although successful single- and two-stage repair for combined coarctation in the presence of severe aortic regurgitation has been described, the surgical management of this lesion remains particularly difficult. The analysis of larger series of patients operated upon for coarctation reveals significant early mortality rate in patients with associated severe aortic insufficiency. Although the exact cause of the acute left ventricular failure remains unclear and is a matter of debate, one can assume that changes in the haemodynamics, resulting in global myocardial ischaemia from impaired coronary blood supply or a massive volume overload of the left ventricle after the correction of the coarctation, could have led to myocardial irritability and left ventricular failure. We present a three-stage repair with subtotal relief of the coarctation by balloon angioplasty and stenting first; elective aortic valve replacement in a second stage and finally total balloon dilatation of the residual stenosis at the previously subtotal dilated coarcted segment.

Genotoxic potential of beta-carbolines: a review.

The mutagenic and co-mutagenic properties of harman, norharman and of some of their pharmacologically important derivatives are reviewed. These compounds do not behave as true mutagens, but rather interact, directly or indirectly with DNA, leading to various consequences. This unusual behaviour is most probably related to the particular structure of the chemical nucleus common to all beta-carbolines which confers to the different derivatives the property to interact with various macromolecules and enzymatic systems. These interactions are compiled and discussed in this review. The alterations, by beta-carbolines, of some important enzymatic systems, e.g. cytochrome P-450, have been clearly demonstrated, yet many discrepancies and contradictions exist so that an interpretation of the results and the definition of some common mechanism appears premature. Since beta-carbolines are widely distributed in tissues and since they may modify and increase genotoxic and toxic consequences of other compounds, these interactions need to be clarified.

The role of cooked food mutagens as possible etiological agents in human cancer. A critical appraisal of recent epidemiological investigations.

The paper reviews the epidemiological studies that investigate the relationships between dietary protein intake and the risk of some cancer and that have been published since 1980. A comparison of these reports is complicated because of many confounding factors that could obscure the conclusions (e.g. choice of controls) and because it is difficult to distinguish the consumption of fat from that of animal proteins. The 75 examined publications deal with the influence of food intake on different cancers: colo-rectal (42), stomach (8), breast (7), ovarian (4), endometrium (3), prostate (4), pancreas (2), urothelium (1), bladder (2), brain (1), lymphoma (1). From these studies in parallel with information from other sources, it is concluded that pyrolysis products generated by heat treatment of protein-rich food could be responsible factors for, at least, colo-rectal cancer.

[In vitro study of the metabolic conversion of aflatoxin B1 into its epoxide]. / Etude, in vitro, de la conversion métabolique de l'aflatoxine B1 en son époxyde.

The conversion of aflatoxin B1 into its epoxide was evaluated in vitro by two different approaches based on HPLC analysis: the quantitative estimation of the tris(OH)AFB1 addition product resulting from the indirect reaction of AFB1-epoxide with tris buffer (hydroxymethyl) aminomethane and on the other hand by the quantification of the formation of the glutathione conjugate (AFB1-SG). The tris(OH)AFB1 is more sensitive than AFB1-SG in fluorescence detection. The AFB1-SG obtained (5.42 +/- 0.42 microgram) is weakly less than the quantity of tris(OH)AFB1 (6.00 +/- 0.72) obtained in the same experimental conditions.

Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci.

We have tested for evidence of linkage between the genetic loci determining concentrations and composition of plasma high density lipoproteins (HDL) with the genes for the major apolipoproteins and enzymes participating in lipoprotein metabolism. These genes include those encoding various apolipoproteins (apo), including apoA-I, apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, apoE, and apo(a), cholesteryl ester transfer protein (CETP), HDL-binding protein, lipoprotein lipase, and the low density lipoprotein (LDL) receptor. Polymorphisms of these genes, and nearby highly polymorphic simple sequence repeat markers, were examined by quantitative sib-pair linkage analysis in 30 coronary artery disease families consisting of a total of 366 individuals. Evidence for linkage was observed between a marker locus D16S313 linked to the CETP locus and a locus determining plasma HDL-cholesterol concentration (P = 0.002), and the genetic locus for apoA-II and a locus determining the levels of the major apolipoproteins of HDL, apoA-I and apoA-II (P = 0.009 and 0.02, respectively). HDL level was also influenced by the variation at the apo(a) locus on chromosome 6 (P = 0.02). Thus, these data indicate the simultaneous involvement of at least two different genetic loci in the determination of the levels of HDL and its associated lipoproteins.

The mutagenicity of nitrite in the Salmonella/microsome test system.

The bacterial strains of Salmonella typhimurium used for detection of base-pair substitutions (TA1530, TA1535, TA100 and TA102) and various types of frameshift mutations (YG1024, DJ400 and DJ460) were exposed to nitrites in the Salmonella/microsome test system. In agreement with published data, nitrites exhibited mutagenic activity in standard strains TA1530, TA1535 and TA100. The TA102 strain was insensitive as were the frameshift tester strains despite their genetically manipulated genome increasing their sensitivity.

Evidence for linkage of the apolipoprotein A-II locus to plasma apolipoprotein A-II and free fatty acid levels in mice and humans.

Although it has been hypothesized that the synteny between mouse and human genes provides an approach to the localization of genes that determine quantitative traits in humans, this has yet to be demonstrated. We tested this approach with two quantitative traits, plasma apolipoprotein A-II (apoAII) and free fatty acid (FFA) levels. ApoAII is the second most abundant protein of high density lipoprotein particles, but its function remains largely unknown. We now show that, in a backcross between strains Mus spretus and C57BL/6J, apoAII levels correlate with plasma FFA concentrations on both chow (P < 0.0001) and high-fat (P < 0.0003) diets and that apoAII levels are linked to the apoAII gene (P < 0.0002). To test whether variations of the apoAII gene influence plasma lipid metabolism in humans, we studied 306 individuals in 25 families enriched for coronary artery disease. The segregation of the apoAII gene was followed by using an informative simple sequence repeat in the second intron of the gene and two nearby genetic markers. Robust sib-pair linkage analysis was performed on members of these families using the SAGE linkage programs. The results suggest linkage between the human apoAII gene and a gene controlling plasma apoAII levels (P = 0.03). Plasma apoAII levels were also significantly correlated with plasma FFA levels (P = 0.007). Moreover, the apoAII gene exhibited linkage with a gene controlling FFA levels (P = 0.003). Evidence for nonrandom segregation was seen with markers as far as 6-12 centimorgans from the apoAII structural locus. These data provide evidence, in two species, that the apoAII gene is linked to a gene that controls plasma apoAII levels and that apoAII influences, by an unknown mechanism, plasma FFA levels. The results illustrate the utility of animal studies for analysis of complex traits.

[In vitro study of clastogenic properties of nitrites and nitrates]. / Etude, in vitro, des propriétés clastogènes des nitrites et des nitrates.

In vitro culture of peripheral blood lymphocytes has been used to evaluate the ability of nitrates (NaNO3) and nitrites (NaNO2) to produce chromosome aberrations in mammalian cells. Whereas treatment with NaNO3 did not increase the spontaneous yield of aberrations, exposure to high doses of NaNO2 resulted in an low increase of micronucleated cells and of chromatid gaps.

Mutagenicity of nitroxyl compounds: structure-activity relationships.

Three piperidinoxyl radicals were found to be directly mutagenic in Salmonella typhimurium TA 100, one pyrrolidinoxyl compound had weaker activity, and two other pyrrolidinoxyl derivatives did not produce an increase of the spontaneous revertants. The tester strain TA 100 was selected in preliminary tests for its higher sensitivity compared to TA 98 and TA 102. The mutagenic activity of the three active compounds was abolished by partial reduction with ascorbic acid, suggesting that the mutagenicity was linked to the free radical nature of these compounds, and reduced in the presence of a cofactor supplemented rat liver subcellular fraction. The mutagenicity of the tested compounds was correlated to the resistance of the nitroxyl spin labels to reduction: the more reactive radicals were found to possess higher mutagenic activity.

Mutagenic potency of heterocyclic amines towards Salmonella typhimurium; possible causes of variability in the results observed.

The potent food mutagens and carcinogens 2-amino-3-methylimidazol[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MEIQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are probably the most active bacterial mutagens so far discovered. Important discrepancies were found, however, in the specific mutagenicities published for these compounds. This paper analyzes a number of experimental factors that could explain these differences: purity of the compounds, stability under the experimental conditions employed, solvents used, bacterial toxicity, testing procedure, amount and age of the S9 fraction, dose-effect relationships, day-to-day variability, origin of the compounds investigated or of the bacterial strain and age of the strain culture used. None of these factors was found to play a critical role, when the other experimental conditions were strictly standardized. The in-house testing procedure used probably explains the interlaboratory variations observed.

[Detoxification of aflatoxin B1 by different chemical methods and evaluation of the effectiveness of the treatments applied]. / Détoxification de l'aflatoxine B1 par différentes méthodes chimiques et évaluation de l'efficacité des traitements appliqués.

Different chemical treatments were applied to solutions of Aflatoxin B1 in order to compare their efficacy for the detoxification of AfB1: sodium sulfite, sodium hydrogen sulfate, sodium hydroxide, ammonia, sodium hypochlorite, hydrogen peroxide. The rate of the detoxification of AfB1 has been followed by three experimental approaches: 1. Quantitative estimation of the unmodified AfB1 by HPLC chromatography. 2. Quantitative estimation of the most toxic metabolite. AfB1-epoxide by chemical transformation into the trishydroxy AfB1 derivative followed by HPLC analysis. 3. Determination of the bacterial mutagenic activity, following the Ames' test. Among the different detoxification methods that were compared, the treatment with sodium sulfite proved to be the most efficient and seems thus to be recommended for foods contaminated by AfB1.

The mutagenicity of cassava (Manihot esculenta Crantz) preparations.

Different cassava products were found to contain mutagenic activities in the Ames test. This paper describes how the flavonol quercetin is released during the cooking of fresh cassava leaves, following a process very similar to culinary habits. The hydrolysis of the glucoside(s) and the release of free quercetin has been followed by the monitoring of mutagenic activities with a simultaneous isolation and purification by thin-layer chromatography. The fluorodensitometric method applied revealed that fresh leaves contained about 1300 mg quercetin per kg wet weight, of which 800 mg were released during a normal cooking process.

Effect of dipyridoimidazole pretreatment on mutagen activation in rats.

Rats were pretreated with a single oral dose of different mutagenic fractions obtained from glutamic acid pyrolysate: Glu-P-2 (2-amino-dipyrido[1,2-a:3',2'-d]imidazole), Glu-P-3 (3-amino-4,6-dimethyldipyrido[1,2-a:3',2'-d]imidazole), the tar residue and a basic extract (B2). The liver S9 fractions of these animals were used to investigate the mutagenic activation of 3 promutagens (2-aminoanthracene, Glu-P-2 and Glu-P-3) in Salmonella typhimurium strain TA1538. Different factors were analyzed; influence of the structure of the compounds administered, doses, time interval between pretreatment and sacrifice and sex of the rats. Interpretation of the hepatic induction effects was complicated, however, by the fact that simple oral pretreatment with the solvents (DMSO or ethanol) enhances the activation of the substrates tested for mutagenicity. A dose-effect relationship was found between 2-AA mutagenic activation and Glu-P-2 pretreatment. Glu-P-3 induced the activation of 2-AA more than did Glu-P-2, in the male as in the female. The mutagenicity of 2-AA activated with S9 from male rats was found to be optimal after 24 h pretreatment with 20 mg Glu-P-2/kg b.w. The mutagenicity of Glu-P-2 was poorly influenced by the different pretreatments applied to either the males or the females, whereas some dose effect was found in the autoinduction of Glu-P-2 mutagenicity. Compared to Glu-P-2, the mutagenicity of Glu-P-3 was increased at higher levels when tested with S9 from males pretreated with the same compound, but no differences were observed between males and females.

A comparative study, with 40 chemicals, of the efficiency of the Salmonella assay and the SOS chromotest (kit procedure).

A comparison was made, for 40 compounds belonging to different chemical classes, of the mutagenicity as measured by the Salmonella assay and of the SOS-inducing potency as measured by the SOS chromotest kit procedure. It was found that most (78%) of the chemicals described as mutagens/carcinogens (14 compounds) were detected with a simplified Ames test procedure, using 3 strains (TA 97, TA 98, TA 100) and 3 concentrations of the tested material. The SOS chromotest, carried out following the recommendations of the commercially available kits, revealed that only 4 Ames test-positive compounds were mutagenic towards E. coli strain PQ 37.