Heterogeneous expression of cyclooxygenase-2 and inducible nitric oxide synthase within colorectal tumors: correlation with tumor angiogenesis.

BACKGROUND: Recent studies have shown that the cyclooxygenase (COX) and the inducible nitric oxide synthase (iNOS) pathways are involved in the development of tumor angiogenesis in human cancers. AIMS: To investigate whether a different pattern of COX-2 and iNOS expression/activity exists within different areas of colorectal tumors and to analyze the relationship between these two enzymes and tumor angiogenesis. METHODS: Microvessel density (MVD) and COX-2, iNOS, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein expression were evaluated at both the invasive front (IF) and the tumor center (TC) in 46 human colorectal cancer specimens. We also investigated the concentration of PGE2 and NO at the same sites. RESULTS: COX-2 and iNOS protein expression and activity were significantly higher within the IF than the TC of the tumor specimens. Similarly, MVD and VEGF/VEGFR-2 expression significantly increased from the TC to the IF. Only COX-2 expression was significantly correlated with MVD and VEGF/VEGFR-2 expression at both the TC and the IF. CONCLUSION: Our study shows a heterogeneous expression of COX-2 and iNOS in colorectal cancer. The up-regulation of COX-2 at the IF parallels an increase in vessel density and VEGF/VEGFR-2 expression, thus supporting the hypothesis that the tumor periphery is the most aggressive portion of a colorectal tumor.

[Retained rectal foreign bodies by trans-anal introduction. Case report]. / Corpi estranei endorettali introdotti per via anale. Case report.

The Authors refer about two cases of retained rectal foreign bodies by trans-anal introduction as consequence of anal eroticism: a deodorant aerosol-can cap and a sizeable phallic object. These reports represent an occasion to talk about the etiology (the wide variety of foreign bodies) and the motivations (eroticism or sadism, clumsy diagnostic and therapeutic procedures, true or presume accidents) responsible for this pathological condition and to consider every therapeutic options employed during the past years, without forgetting that, despite difficulties, non-surgical extraction is to prefer, if possible, because of the negative prognostic implications often related to the surgical treatment. The Authors finally confirm, because of the severity of this pathological condition - with negative outcomes especially in that cases with complete or incomplete perforative complications (produced during introduction through the anus or during several attempts of extraction of the object or caused by its long staying in the rectum because of the patient's denial of medical care) - the surgeons can't put aside possible indication for surgical treatment.

[Idiopathic ischaemic infarction of the stomach. Case report]. / Infarto ischemico idiopatico dello stomaco: case report.

Idiopathic ischaemic infarction of the stomach is an extremely rare condition since only 2 other cases have been published in the Literature so far. The Authors report a case of such entity on a 75 year old male patient, admitted from the accident and emergency department because of a upper digestive tract haemorrhage with clinical signs of hypovolemic shock. The patient subsequently underwent an upper gastro-intestinal endoscopy that suspected an ulcerated gastric neoplasm. The patient therefore underwent a total gastrectomy and was discharged home on p.o. day X. The pathology report showed an Ischaemic infarction of gastric mucosal tissue with pomphoid Oedema of submucosal layer. Ulcerative superficial necrosis with venous haemorragic swarm and focal acute pseudomembranous inflammation. Not neoplastic features. Etiopathogenetic, pathophisiologic ipoteses and clinical implication of Idiopathic ischaemic infarction of the stomach are discussed.

[Strangulated pelvic internal hernia: early postoperative complication of sacral colpopexy with prosthesis]. / Ernia interna pelvica strozzata quale complicanza postoperatoria precoce di colposacropessi con protesi.

The Authors report a case of internal strangulated hernia in a patient operated of colposacropexy for vaginal prolapse following total hysterectomy. The diagnosis was formularized by abdominal TC consenting the surgical treatment by bowel loop resection completed by pelvic floor reconstruction.

[Inguinal hernioplasty: Shouldice vs. tension-free techniques. A personal experience]. / L'ernioplastica inguinale: metodiche a confronto (Shouldice vs. tecniche "tension-free"). La nostra esperienza.

The Authors report their experience with the use of Shouldice technique and tension-free procedures (Lichtenstein, Trabucco). They evaluate long time results with both procedures making a comparasion of Shouldice versus tension-free. The results evaluation underlines the best performance of tension-free procedures with elimination of recurrence. The Authors achieve that the tension-free techniques are now the gold standard for surgical treatment of groin hernia.

[Acute bleeding in gastrointestinal stromal tumor: case report]. / Enterorragia acuta da tumore stromale gastrointestinale (GIST). Contributo clinico.

A.A. refer a case report on a patient observed in emergency condition for acute bleeding from digiunal bowel by a GIST. Starting from clinical case, describe a brief profile of clinical, histogenetic, diagnostic and prognostic characteristics of the GIST also delineated by recent reports from literature; agree with other A.A. about treatment procedure represented always by resection of affected intestinal tract and never by enucleation for inconstant and unforeseeable biologic comportment by this tumours.

[Gastrointestinal stromal tumors]. / I tumori stromali gastrointestinali.

The Authors report two cases of GIST and underline cytogenetic, clinic and prognostic aspects of this disease; they describe as well new histo-cyto-genetic data that identify as origin tissue interstitial cells of Cajal, by immunohistochemical and genetic tests. They also consider new diagnostic and therapeutic options based on surgical treatment. Finally controversial prognostic problems are discussed.

Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats.

Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leukocyte infiltration, upregulation of the expression of intercellular adhesion molecule 1 (ICAM-1) and upregulation of P-selectin in the colon. Here, we investigate the effects of the selective cyclo-oxygenase-2 inhibitor, celecoxib, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced hemorrhagic diarrhoea and weight loss. At 4 days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology, as well as an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin, as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) polymerase showed intense staining in the inflamed colon. Celecoxib (5 mg/kg twice a day orally) significantly reduced the degree of hemorrhagic diarrhoea and the weight loss caused by administration of DNBS. Celecoxib also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in myeloperoxidase activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde, (iv) the increase in staining (immunohistochemistry) for nitrotyrosine, as well as (v) the upregulation of ICAM-1 and P-selectin caused by DNBS in the colon. Thus, we provide the first evidence that a selective cyclo-oxygenase-2 inhibitor celecoxib reduces the degree of colitis caused by DNBS.

Inducible nitric oxide synthase knockout mice exhibit resistance to the multiple organ failure induced by zymosan.

In the present study, by comparing the responses in wild-type mice (+/+) and mice lacking (-/-) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of non-septic shock. A severe inflammatory response characterized by peritoneal exudation, high peritoneal levels of nitrate/nitrite, and leukocyte infiltration into peritoneal exudate was induced by zymosan administration in iNOS +/+ mice. This inflammatory process coincided with the damage of lung, liver, and small intestine, as assessed by histological examination. Lung, small intestine, and liver myeloperoxidase (MPO) activity, indicative of neutrophil infiltration and lipid peroxidation, were significantly increased in zymosan-treated iNOS +/+ mice. Peritoneal administration of zymosan in the iNOS +/+ mice induced also a significant increase in the plasma levels of nitrite/nitrate and in the levels of peroxynitrite at 18 h after zymosan challenge. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine and to poly ADP-ribose synthetase (PARS) in the lung, liver, and intestine of zymosan-treated iNOS +/+ mice. The intensity and degree of nitrotyrosine and PARS were markedly reduced in tissue section from zymosan-iNOS -/- mice. Zymosan-treated iNOS -/- mice showed a significantly decreased mortality and inhibition of the development of peritonitis. In addition, iNOS -/- mice showed a significant protection on the development of organ failure since tissue injury and MPO were reduced in lung, small intestine, and liver. Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage, and reduction of cellular levels of NAD+ was observed in ex vivo macrophages harvested from the peritoneal cavity of iNOS -/- mice subjected to zymosan-induced non-septic shock. In vivo treatment with aminoguanidine (300 mg/kg 1 and 6 h after zymosan administration) significantly prevents the inflammatory process. Taken together, our results clearly demonstrate that iNOS plays an important role in zymosan-induced non-septic shock.

Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat.

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor alpha, and interleukin 1beta. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an decrease in mitochondrial respiration, and partially restored the cellular level of NAD+ in ex vivo macrophages harvested from the pleural cavity of rats subjected to carrageenan-induced pleurisy. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role.

Calpain inhibitor I reduces colon injury caused by dinitrobenzene sulphonic acid in the rat.

BACKGROUND AND AIMS: Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis. METHODS: Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulphonic acid (DNBS). RESULTS: Rats experienced haemorrhagic diarrhoea and weight loss. Four days after administration of DNAB, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as by an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed intense staining in the inflamed colon. Staining of sections of colon obtained from DNBS treated rats with an anti-cyclooxygenase 2 antibody showed diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. Calpain inhibitor I also caused a substantial reduction in (i) degree of colon injury, (ii) rise in myeloperoxidase activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv) increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the colon. CONCLUSION: Calpain inhibitor I reduces the degree of colitis caused by DNBS. We propose that calpain inhibitor I may be useful in the treatment of inflammatory bowel disease.

Beneficial effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure induced by zymosan in the rat.

BACKGROUND AND METHODS: We investigated the effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure (MOF) caused by zymosan in the rat. Zymosan (500 mg/kg, suspended in saline solution, ip) enhances formation of reactive oxygen species, which contribute to the pathophysiology of MOF. After zymosan or saline administration, animals were monitored for 12 days. RESULTS: Treatment of rats with tempol (10, 30, or 100 mg/kg ip, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Tempol also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in the concentrations of myeloperoxidase and malondialdehyde caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose)synthetase demonstrated a positive staining in lung, liver, and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose) synthetase was markedly reduced in tissue sections obtained from zymosan-treated rats that had received tempol (100 mg/kg ip). Furthermore, treatment of rats with tempol significantly reduced the following: a) the formation of peroxynitrite, b) the DNA damage, c) the impairment in mitochondrial respiration, and d) the decrease in the cellular concentration of oxidized nicotinamide adenine dinucleotide observed in macrophages harvested from the peritoneal cavity of rats treated with zymosan. CONCLUSION: This study provides the first evidence that tempol, a small molecule that permeates biological membranes and scavenges reactive oxygen species, attenuates the degree of MOF associated with zymosan-induced peritonitis in the rat.

[Diaphragm rupture caused by closed trauma. A more and more frequent condition]. / La rottura del diaframma da trauma chiuso. Una patologia di sempre più frequente riscontro.

The Authors report a case of rupture of the diaphragm in blunt trauma of the abdomen, to examine the more significant features of this condition whose incidence proves to be increasing, after a review of the literature data, parallel to the increase of accidents on the road and at work. They examine the most important pathogenic problems and these related to the mechanism leading to diaphragmatic lesion and they highlight the deeper pathophysiological changes suffered from the patient with such a condition. They draw attention to what they consider to be the most important aspect, and therefore the diagnosis. In fact, in accordance with the various series of cases reported in the literature, it is crucial in the diagnostic problem is when the possible cause of the rupture is suspected and necessary diagnostic cascade (Rx, echotomography, TC) is activated so to highlight the lesion. Therefore a quick diagnostic fitting is necessary for the survival of the acute patient with hernia of the thorax cavity, as well as quick surgical correction of the lesion that, as in the case described, serves to achieve the best possible anatomic-functional results.

[Authors' experience with the role of preoperative ultrasonography in the study of benign lesions of the gallbladder]. / La nostra esperienza sul ruolo dell'esame ecografico preoperatorio nello studio delle lesioni parietali benigne della colecisti.

The benign parietal lesions of the gallbladder are diseases that, as known, found their pathogenetic moment on hyperplasia of constituent tissues of the gallbladder wall and comprises the controversial chapter of "cholecystosis". The Authors, to contribute to their better clinical and pathogenetic staging, report their experience on 25 cases. They debate on the usefulness of ultrasonography, surely a diagnostic progress for these formations, which are small structures more or less echogenic and that they develop in the gallbladder; the echographic imaging, for its sharpening, has substituted the cholecystographic procedure. The aim of present study is to analyse the results obtained by using echography as diagnostic preoperative procedure of "cholecystosis". The ultrasonography supplies the surgeon an indication to prophylactic surgical treatment as single, effective procedure in preventing the gallbladder carcinoma.

[Our experience in using a synthetic prostacyclin analog in the treatment of critical ischemia of the extremities]. / La nostra esperienza sull'utilizzo dell'analogo sintetico della prostaciclina nel trattamento dell'ischemia critica degli arti.

The authors, after examination of pharmacologic profile of Iloprost, prostacyclin synthetic analogue, report their clinical experience from January 1992 to June 1997 on 105 patients with severe ischaemia of inferior limbs. They utilize two protocols: 0.5-2 ng/kg/min x 6 hs once a day x 28 days and 1-1.5 ng/kg/min x 6 hs twice a day x 12 days. The first protocol were practise along the first 2 years; the second on following period as long as today. The results, evaluated on clinical criteria, are referred entity and time of pain remission and decrease of analgesic use, performance status improvement, increase of gear autonomy and, if present, wound healing. The incidence of amputation was 4.76% (5 pts). The authors issue that Iloprost is a conservative treatment, often alternative with amputation, giving sometimes to patients a longtime functional "restitutio ad integrum".

[Clinical considerations and therapeutic options in papillomatosis of common bile duct. Clinical case]. / Considerazioni cliniche ed opzioni terapeutiche nella papillomatosi della via biliare principale. Caso clinico.

The Authors report a case of endoscopic treatment of common biliary tract papillomatosis. This therapeutic option derive by patient's clinical evaluation and clinical reports from literature. Agreeing with Cornud, we have opted for endoscopic conservative management with drainage of common biliary tract; furthermore endoscopic procedure permit, by an intensive follow-up, identification and management of possible recurrences. This approach, minimally invasive, is in our opinion the first option for the biliary papillomatosis management.

[Spigelian hernia: clinical, diagnostic and therapeutical aspects]. / L'ernia di Spigelio: aspetti clinici, diagnostici e terapeutici.

The Authors describing a case of Spigelian hernia observed point out clinical, diagnostic and therapeutic considerations about this rare pathology of abdominal wall. They specify the anatomic characteristics of the region and underline as any diagnostic difficulties are by passed by use of USG and TC imaging for formulation of correct preoperative diagnosis. They confirm as surgical treatment by a correct access isn't different by a normal hernioplasty and guarantee the long term surgical outcome.

[Intercostal incisional hernia: case report]. / Il laparocele intercostale: caso clinico.

The authors report a case of intercostal incisional hernia following marsupialization of liver hydatid cyst stressing the considerable rarity of the pathology and describing the restorative procedure by intercostal plastic with polypropilene Mesh and rib's approach with stainless steel wires.

[Necrotizing fasciitis: apropos of a case]. / La fascite necrotizzante: a proposito di un caso.

Necrotizing fasciitis is an infection which involves soft tissues up to the fascia, with wide areas of necrosis, and is mainly caused by group A beta-hemolytic Streptococcus. The Authors report a case recently observed and after an accurate review of the Literature, taking into account the most recent pathogenetic knowledges, confirm the necessity of an early diagnosis based on clinical criteria but above all on histological biopsy. The treatment is mainly surgical, and allows, together with the medical treatment, to subdue the rapid progression of the infection which notwithstanding maintains an high mortality rate.

[Inguinal hernia repair in the elderly: modified Shouldice procedure, 10 years of experience]. / L'ernioplastica inguinale sec. shouldice modificata nel paziente anziano. 10 anni di esperienza.

Authors relate their experience of 10 years period (1984-1994) with Shouldice technique for inguinal hernia repair in the elderly. This technique, in the Author's clinical practice, replaced the Bassini operation. The personal series is costituted of 190 patients underwent to inguinal repair during a 10 years period from 1984 to 1994 with recurrence rate of 1.1% (2 pt.). Authors consider Shouldice operation to be most valid from the methods of direct suture, with lower recurrence range.