Mario Nano

Pro-oxidant and proapoptotic effects of cholesterol oxidation products on human colonic epithelial cells: A potential mechanism of inflammatory bowel disease progression

With the aim of investigating whether cholesterol oxidation products could contribute to the pathogenesis of the intestinal epithelial barrier dysfunction that occurs in human inflammatory bowel disease (IBD), differentiated versus undifferentiated CaCo-2 cells, an accepted model for human intestinal epithelial cells, were challenged with a dietary-representative mixture of oxysterols. Only differentiated colonic cells were susceptible to the proapoptotic action of the oxysterol mixture, checked both by enzymatic and by morphological methods, mainly because of a very low AKT phosphorylation pathway compared to the undifferentiated counterparts. Enhanced production of reactive oxygen species by a colonic NADPH oxidase hyperactivation seemed to represent the key event in oxysterol-induced up-regulation of the mitochondrial pathway of programmed death of differentiated CaCo-2 cells. These in vitro findings point to the pro-oxidant and cytotoxic potential of cholesterol oxidation products, of both dietary and endogenous origin, as an important mechanism of induction and/or worsening of the functional impairment of enteric mucosa that characterizes IBD.

Ligation of the Inferior Mesenteric Artery in the Surgery of Rectal Cancer: Anatomical Considerations

Background: No agreement has been found in the literature concerning the safest point of ligation of the inferior mesenteric artery (ima) in order to avoid nerve damage during the surgery of rectal cancer. Study Design: The distance between the origin of the ima and the left paraortic trunk was measured, as was the distance between the left paraortic trunk and the origin of the left colic artery (lca). The measurements were carried out on 20 cadavers and during 22 operations for rectal cancer. Results: The left paraortic trunk always runs posterior to the ima: its distance from the origin of the ima is on average 1.2 cm; the distance of the left paraortic trunk from the origin of the lca is on average 0.4 cm. The point at which the ima and the left paraortic trunk cross varies greatly, but it is never near the origin of the ima. Conclusions: From an anatomical point of view the safest point of ligation of the ima is at its origin. At this point, the left paraortic trunk never runs; so there isn’t any risk to damage the nerve involving it during the ligation of the artery.

Contribution to the surgical anatomy of the ligaments of the rectum.

PURPOSE: Many authors have discussed the presence and the importance of the lateral ligaments of the rectum. Our contribution aims at clarifying some aspects of surgical anatomy that help in the preservation of the urogenital functions and may influence the surgical practice. METHODS: From 1994 to 1998 we examined 27 fresh cadavers and five embalmed pelves. We performed all dissections with a technique similar to that used for the surgical mobilization of the rectum. RESULTS: The lateral ligaments of the rectum are trapezoid structures originating from mesorectum and are anchored to the endopelvic fascia; as lateral extensions of the mesorectum, they must be included in the surgical specimen. According to our results, three main structures can be recognized laterally to the rectum: 1) the lateral ligament, which does not contain important structures; 2) the inferior hypogastric plexus and the urogenital bundle; and 3) the lateral neurovascular pedicle of the rectum that comprises the nervi recti and the middle rectal artery, both running under the lateral ligament, although at different angles. CONCLUSION: At the point of insertion into the endopelvic fascia, the lateral ligaments run close to the urogenital bundle. Nevertheless, the dissection at its attachment is safe if the urogenital bundle is kept under visual control.

Primary duodenal adenocarcinoma

Aims and Background Primary duodenal adenocarcinoma is a rare tumor with a poorly defined natural history and prognostic factors. It presents with nonspecific symptoms, and for this reason the diagnosis is often delayed. It is a serious problem for the surgeon because of the difficulty in obtaining an early diagnosis and standardizing basic tenets for an appropriate surgical approach. The aim of this work was to conduct a review of the literature analyzing the points most frequently debated about this pathology. Methods and Study Design A bibliographic search was carried out on the main search engines to find studies regarding duodenal adenocarcinoma, published in English, from January 1992 to January 2007. Results A total of 19 articles was selected. Results concerning symptoms, location of the tumor, diagnostic examinations, surgical treatment, histopathology of the tumor, survival and follow-up were obtained and discussed. Conclusions All patients who are medically fit to undergo surgery should be given the option of aggressive resection regardless of tumor size, tumor invasion or appearance of positive lymph nodes. Hopefully, an early diagnosis will correlate with improved long-term survival.

Inflammatory and redox reactions in colorectal carcinogenesis

It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment.

Progressive Increase of Matrix Metalloprotease-9 and Interleukin-8 Serum Levels during Carcinogenic Process in Human Colorectal Tract

Background Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues. Methodology/Principal findings 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. Conclusions Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only.

Wound defects in the elderly: our experience

Patients and methods To assess the safety and efficacy of laparoscopic [1-5] primary inguinal and incisional repair we reviewed the records of our patients of over 70 years old, who underwent such a procedure from June 2007 to September 2010: hernia defect size, recurrence, operative time, and procedure-related complications [6] were evaluated and a laparoscopic approach was attempted in all patients who required a mesh repair. We scheduled 42 patients (32 M 10 F, with 53 wound defects totally) for laparoscopic incisional [7] and primary inguinal hernia repair and we performed 17 surgical repair for incisional hernia and 36 for primary hernia. Of those, 13 were done for incisional hernias with a single defect (24.5% recurrence hernias), 4 with multiple defects (7.54% recurrence hernias), 12 were performed for unilateral inguinal hernias (22.56 % recurrence hernias), 16 for bilateral inguinal hernias (30.08 % recurrence hernias), 4 for umbilical hernias (1 recurrence hernias), 2 for epigastric and linea alba’s hernias, and 2 for rectum diastasis. The majority of the patients were normal weight with a mean BMI of 25 kg/m2 (45%), 38% 25 > BMI > 30 (overweight), 17% BMI > 30 (obesity). There was no conversion to an open procedure. The mean operative time was 128 minutes (range: 50 – 325). In all the patients only mesh was used (37.5% polypropylene not reabsorbable, 42.5% tridimensional polyestercollagen composite mesh, 20% lightweight multifilament mesh partly reabsorbable) [8]. The meshes were fixed in 82.5 % with absorbable fixation device, in 5% with a non-absorbable device and in 12.5 % with fibrin glue [9]. In contrast to other authors [10-13], major complications were 14.24% (6/42: 2 chronic inguinal pain, 4 recurrences). Minor complications were 5/42 (11.90%) and included only asymptomatic seromas that were aspirated. The mean hospital stay was 4.7 days (range: 1-18 days).

Elective and emergency laparoscopic cholecystectomy in the elderly: early or delayed approach

Materials and methods From January 2005 to December 2009 114 laparoscopic cholecystectomy in the elderly were performed in our surgical division: 67 for gallbladder stones and 47 for acute cholecystitis. The diagnosis of cholecystitis and gallbladder stones was based on general condition, physical examination, laboratory, radiological findings and sepsis score. For the study we’ve also considered: total hospital stay, timing after and before the operation, kind and duration of operation, conversion to the open procedure, drain and final pathological results. From this study 29 patients were excluded (17 for choledocolytiasis associated and 12 for hospitalisation > 20 days). We hadn’t excluded patients ASA III and ASA IV: in these patients (27.4 %, 17 ASA III and 4 ASA IV) abdominal pressure not superior of 10 mmHg was used [1]. Elderly patients included in the study were 85 (49 M, 36 F). Ordinary Cholecystectomy were peformed in 45 cases and Emergency Cholecystectomy in 40 cases. This last group was further divided into two groups [2-4]: DEA Early, E-DLC, (31 patients operated on within 72 hours from onset of symptoms) and DEA Delayed, DDLC, (9 patients operated on after 72 hours to 9 days from onset of symptoms). We’ve also considered the operating team (Table 1) that performed the operation because the first operator’s experience was considered as an important factor in order to evaluate our results [5-11].

The mesorectum: hypothesis on its evolution

AbstractBackgroundTwo points are controversial in the anatomy of the mesorectum: (1) its origin; and (2) the existence of the lateral ligaments. We studied these structures in animals and in human fetuses.MethodsDissections were performed on quadrupedal mammals (29 dogs and 32 pigs) and 28 primates (Macaca apes). Moreover, macroslices of Macaca ape and of 182 human fetuses were examined histologically.ResultsIn quadrupedal mammals, we found no traces of any adipose masses comparable to the human mesorectum nor were there ligaments of suspension. In the ape, the adipose tissue in the mesosigmoid forms an adipose cuff that completely surrounds the extraperitoneal rectum. Two dense connective bands were found between the lateral wall of the pelvis and the perirectal tissue. Both the mesorectum and the lateral ligaments were clearly identified in the sections of human fetus only at the end of the fifth month but not earlier.ConclusionsOn the basis of our analysis of 3 animal species, we conclude that the mesorectum and lateral ligaments are absent in quadrupedal mammals but are present in primates. Therefore, we hypothesize that these structures appeared with the attainment of the upright position, even though other hypotheses are possible.

Vascular Anatomy of the Rectal Stump After Total Mesorectal Excision

PurposeFor many years, poor vascularization of the short rectal stump has been considered the main cause of leakage. The purpose of this study was to evaluate the vascularization of the rectal stump after total mesorectal excision.MethodsWe studied the iliac vascularization on 28 volunteers with healthy rectum to have an anatomic basis. Then, we studied the vascularization of the rectal stumps after total mesorectal excision by using angio computed tomography at seven and three months after operating on 22 patients; we validated this technique by studying the vascularization using angio computed tomography in 18 rectal specimens from cadavers.ResultsBoth in healthy rectums and in rectal stumps after total mesorectal excision, there is good vascularization substained by middle and inferior rectal arteries. The former is more important and frequent as described in previous literature.ConclusionsThe vascularization of the short rectal stump is generally well represented even after total mesorectal excision.