Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2.

The mechanism(s) involved in the development of pulmonary hypertension (PH) in COPD is still the object of investigation. Cigarette smoke (CS) may lead to remodelling of intrapulmonary vessels and dynamic changes in vascular function, at least in some smokers. A role for proteases in PH has been recently put forward. We investigated, in smoking mice, the role of protease-activated receptor (PAR)-2 in the pathogenesis of PH associated with emphysema. We demonstrated that CS exposure can modulate PAR-2 expression in mouse lung. Acute CS exposure induces in wildtype (WT) and in transgenic mice over-expressing PAR-2 (FVB(PAR-2-TgN)) a similar degree of neutrophil influx in bronchoalveolar lavage fluids. After chronic CS exposure WT and FVB(PAR-2-TgN) mice show emphysema, but only transgenic mice develop muscularisation of small intrapulmonary vessels that precedes the development of PH (~45% increase) and right ventricular hypertrophy. Smoking in FVB(PAR-2-TgN) mice results in an imbalance between vasoconstrictors (especially endothelin-1) and vasodilators (i.e. vascular endothelial growth factor, endothelial nitric oxide synthase and inducible nitric oxide synthase) and enhanced production of growth factors involved both in fibroblast-smooth muscle cell transaction (i.e. platelet-derived growth factor (PDGF) and transforming growth factor ß) and vascular cell proliferation (PDGF). PAR-2 signalling can influence the production and release of many factors, which may play a role in the development of PH in smokers.

Laparoscopic treatment of incarcerated hernia through right broad ligament in patients with bilateral parametrium defects.

We present the first case reported in the literature of small bowel obstruction due to internal incarcerated hernia through a diagnosed bilateral broad ligament defect, and treated by laparoscopy. A 36-year-old white woman, gravida 0, para 0, was admitted to our hospital with intestinal obstruction symptoms. A laparoscopic approach was performed with 3 trocars and internal incarcerated hernia due to a defect in the right broad ligament was found. There was a similar defect in the left broad ligament. The small bowel, once reduced, appeared viable. Closure of both defects was carried out by laparoscopy with 2-0 monofilament absorbable running suture. The patient's postoperative course was unremarkable and she was discharged from the hospital 4 days after the surgical procedure. The classification of defect was a bilateral fenestrae type I defect. Congenital ethiology is plausible because of the presence of bilateral defects and the absence of surgical trauma, pregnancy, pelvic inflammatory disease, endometriosis in the clinical history.

[Short-term results in colorectal surgery. Statistical analysis about mortality, morbidity and hospital stay]. / Risultati a breve temine della chirurgia colo-rettale. Studio statistico su mortalità, morbilità e tempi di degenza.

AIM: The surgical approach on the colon and rectum represents a wide slice of the surgical procedures carry out in election or emergency in a general surgery unit. The literature reports prospective and retrospective studies evidencing emergency surgery, advanced age, comorbidity and other factors can determinate a worsening of short-term outcome (postoperative mortality, morbidity and hospital stay). The aim of the study was to verify, through a statistical analysis on a group of patients operated on the colon and the rectum, which are the factors weighting on the short-term outcome. METHODS: Our retrospective study is carried out on 150 patients consecutively operated on the colon and rectum from January 2002 to September 2004 in elective or emergency surgery in the Unity of General Surgery of the Hospital S. Maria Nuova Azienda Sanitaria of Florence. The variables for the statistical analysis were: sex, age, comorbidity, nature of pathology, timing of surgery, type of emergency, lesion location, surgical intervention, presence of social factors delaying the discharge, blood transfusion, Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM-score). RESULTS: The mortality study found the advanced age (>70 years) as risk factor in the univariate analysis, not confirmed in the multivariate one. The morbidity study found advanced age, presence of comorbidity and blood transfusion as risk factors in the univariate analysis, not confirmed in the multivariate one. The POSSUM-score represents in both multivariate analyses the only statistically meaningful parameter correlated with mortality (P<0.005) and morbidity (P<0.05). The multivariate analysis in the study on the hospital stay found that more staged surgery carry to a lengthening of hospital stay (P<0.0001); in minor such measure blood transfusion (P=0.0005), emergency surgery (P=0.002) and presence of social factors (P=0.008); comorbidity (P=0.02) and advanced age (P=0.03) had less statistical weight. CONCLUSIONS: Despite of the literature, this study found none of the analyzed variables related on postoperative mortality and morbidity in statistically meaningful way. The POSSUM-score demonstrated once again validity in estimating the probability of dead and of postoperative complications. The variables that influenced in lengthening of hospital stay were: more staged surgery, blood transfusion, emergency surgery, presence of social factors conditioning the discharge, comorbidity and advanced age of the patients. The good results about mortality and morbidity can be explained by the fact we prefer in emergency more staged surgery that protect the patients from complications related to the anastomosis, the presence of sub-intensive surgical beds with a constant monitoring of high risk patients and the close collaboration between surgeons and intensive care medical doctors.

[Abdominal tuberculosis: clinical features, diagnosis and role of surgery]. / La tubercolosi addominale: aspetti clinico-diagnostici e ruolo della chirurgia.

AIM: Nowadays the incidence of tuberculosis is increasing in some population groups (subjects immigrated from developing countries, affected from HIV infection, or undergoing immunosuppressive therapy) and to the development of multidrug-resistance. The clinical manifestations, routine laboratory and radiographic analyses of abdominal tuberculosis are nonspecific and surgery plays a fundamental role because 25-75% of such patients are operated. METHODS: Six patients, 4 male and 2 female (age 23-62 years) underwent laparotomy or laparoscopy. Five patients were not European, 1 was Italian. The surgical indications were: intestinal occlusion in 3 patients; perforation in 1 patient; peritonitis in 2 patients. RESULTS: The most frequent clinical manifestations were pyrexia, weight loss, anemia, ascites. Chest X-ray was normal in all patients. All patients were found ARB-negative in sputum and in ascitic fluid, while 1 was positive to culture of sputum and 3 of ascitic fluid. In all patients histopathologic examination showed typical findings of tuberculosis. CONCLUSIONS: The surgical indication is made for diagnostic aim or due to the presence of complications. Laparoscopy is the gold standard in the diagnosis,since it allows whole exploration of abdomen and taking of sample for biopsy and ascitic fluid to find micobacterium. In fact, abdominal tuberculosis is a paucibacillar disease and rarely it is possible to demonstrate the direct presence of M. Tuberculosis, but nowadays the methods of the genome amplification allow to demonstrate the sequence of the chromosomial DNA of M. Tuberculosis from small fragments of bioptic material.

[Endometriomas of the abdominal wall: Imaging findings]. / Endométriomes de la paroi abdominale: apport de l'imagerie.

Endometrioma of the abdominal wall is a not well-recognized disease and usually develops after pelvic surgery. The most common presentation is a mass of the abdominal wall associated with pain during menstruation. We report six cases of parietal endometriomas studied with ultrasonography, CT, and in one case with MRI. Our results are compared with recent findings in the literature. The purpose of this study was to describe the clinical and imaging findings in abdominal wall endometriomas that can help reach a presurgical diagnosis.

[Transitional carcinoma of the ureter and urinary tuberculosis]. / Carcinoma transizionale dell'uretere e tubercolosi urinaria.

Tumors of the renal pelvis are rare neoplasms: their yearly incidence is 1.4 cases per 100,000 men and 0.6 cases per 100,000 women. The annual incidence of renal tuberculosis is 13 cases per 100,000 persons. The likelihood of both diseases occurring in the same kidney is extremely remote. We report on a case of ureter transitional cell carcinoma developed in a patient with tuberculosis stenosis of the same ureter, small retracted bladder and destruction of the opposite kidney. Total uterectomy, augmentation ileocaecocystoplasty and contralateral nephrectomy were performed. Literature is briefly reviewed and is underlined too the paradoxical simultaneous occurrence of transitional cell carcinoma and active tuberculosis infection, while the use of the bacillus of Calmette-Guerin is being advocated in the treatment of urotelial tumors.

Augmentation ileocystoplasty in a case of eosinophilic cystitis.

Eosinophilic cystitis (EC) is a rare form of bladder inflammation characterized by massive eosinophilic infiltration of the bladder wall. The most frequent signs and symptoms are pollakiuria, urgency, macroscopic haematuria and hypogastric pain: the involvement of the ureters may cause hydronephrosis and renal failure. Eosinophilia and eosinophiluria are present in 35% and in 50% of the cases respectively. EC may evolve towards sclerosis up to the anatomoclinical picture of small retracted bladder, which requires to be differentiated from tubercular cystitis, interstitial cystitis and cancer. Imaging techniques are not definitely diagnostic. Diagnosis can be reached only by biopsy with the microscopic demonstration of eosinofilic infiltration of the whole bladder wall in the early and acute stages, while fibrosis with poor cellularity predominates in the chronic stages. Etiology is unknown and the hypothesis of an allergic origin is unproved even though remissions or recoveries induced by steroidal therapy have been reported. Surgical therapy of EC, as in our observation, is absolutely required to correct urgency and incontinence and to prevent renal failure when the urinary upper tract has been primarily or secondarily involved.

Comparing two modalities of screening for prostate cancer: digital rectal examination + transrectal ultrasonography vs. prostate-specific antigen.

AIMS AND BACKGROUND: To evaluate the performance and feasibility of screening for prostate cancer by comparing screening modalities. METHODS: Prospective study of two comparable cohorts of healthy resident males aged 60 to 75 years. Screening attenders in the two invited cohorts were screened either by digital rectal examination (DRE) and transrectal ultrasonography (TRUS), or by serum prostate-specific antigen determination (PSA: cutoff 4 ng/ml). Attendance and biopsy rates, predictive values, prevalence of screen-detected cancers, as well as screening costs were determined, and the efficiency of the two screening modalities was compared. RESULTS: 1425 subjects were screened by DRE+TRUS. Attendance rate was 33.7%, the biopsy rate was 2.7%, and the prevalence of detected cancers was 1.82%. A total of 1315 subjects was screened by PSA. Attendance rate was 66.9%, the biopsy rate was 2.8%, and the prevalence of detected cancers was 1.67%. Screen-detected cancer stage was more favorable than observed in clinical practice, and early detection was evident, with the prevalence/incidence ratio higher than 10:1 in both programs. The cost per subject screened was about 34,000 Lire for DRE+TRSU and about 30,000 Lire for PSA program. CONCLUSIONS: The study confirms that early detection of prostate cancer is possible and that screening is practically feasible. Both screening modalities achieved comparable results as regards early detection, but screening by PSA had a higher compliance and lower costs. PSA seems the ideal test to be used in prospective controlled studies aimed at demonstrating screening efficacy.

[Comparison between 2 techniques of screening for prostatic carcinoma. Rectal exploration and transrectal ultrasonography vs. prostate specific antigen]. / Confronto tra due modalità di screening per il carcinoma prostatico. Esplorazione rettale ed ecografia transrettale vs. antigene prostatico specifico.

We report the results of two pilot studies for the early detection of prostatic carcinoma in resident men aged 60-75 years, using combined digital rectal examination (DRE) and transrectal ultrasonography (TRUS) versus prostate-specific antigen (PSA; cutoff: 4 ng/ml) as screening tests. Both screening protocols exhibited high cancer detection rates (DRE + TRUS = 1.82%, PSA = 1.67%), with a high prevalence/incidence ratio (observed/expected ratio: DRE-TRUS = 13.8:1, PSA = 11.3:1) and a diagnostic anticipation of about 6-7 years. Stage (DRE + TRUS: A = 0%, B = 69%, C-D = 31%; PSA:A = 14%, B = 77%, C-D = 9%) and grading distribution (no case with Gleason score < 5) suggests that most screen-detected cancers were clinically assessable but the extent of overdiagnosis of latent carcinomas cannot be estimated. Both screening protocols proved to be cost-effective (biopsy rate: DRE + TRUS = 2.7%, PSA = 2.8%; cost per screened subject: DRE + TRUS = L. 33,750, PSA = L. 30,400; cost per cancer detected: DRE + TRUS = L. 1,854,000, PSA = L. 1,817,500) but screening by PSA was much better accepted (attendance rate: DRE + TRUS = 33.7%, PSA = 66.9%), which makes it the screening test of choice for controlled studies on screening efficacy. This study allows no definitive conclusions to be drawn on screening efficacy but confirms only that screening is feasible at a reasonable cost and yields high diagnostic anticipation. Whether this benefits the screened population is currently debated and needs to be confirmed by controlled studies. Screening may have upsetting negative outcomes such as overdiagnosis, overtreatment, increased treatment-related mortality rates and worsened quality of life, and there is no evidence supporting the recommendation of screening as a routine practice.

[Early observations of pancreatic ultrastructure during hemorrhagic necrosis in the rat with closed duodenal pouch]. / Prime osservazioni ultrastrutturali sulla necrosi emorragica del pancreas nel ratto con tasca duodenale chiusa.

Many problems are still unanswered in the pathogenesis of acute clinical and experimental pancreatic necrosis. A new technique which can be performed in the rat seems a suitable model for reflux pancreatic necrosis without artificial pressure changes in the ductal system. A closed duodenal loop is obtained with ligation proximal and distal to Vater's ampulla and a gastroenteroanastomosis is associated to avoid intestinal obstruction. All the rats die with hemorrhagic pancreatic necrosis in 36 hours. After 12 hours from the operation ductal and acinar lumina are enlarged. In the centroacinar and intercalated duct cells some lysosomes and mitochondria with clear matrix and reduced cristae are detected. Intercellular junctions in ducts and acini have normal morphology. In the basal cytoplasm of acinar cells some prominent autophagic vacuoles are detectable. After 24 hours in the acinar cells autophagic vacuoles are greatly increased and basal cytoplasmic degeneration often occurs, with plasmalemma and basal lamina interruptions. Intercellular junctions are apparently unaffected until cell necrosis sets in. In blood capillaries endothelial cells are swollen, fibrin thrombosis, hemorrhage and leucocyte infiltration are often detectable. As lysosomal activity occurs also in different kinds of experimental pancreatic necrosis, it could be a common pathogenetic factor, responsible for hydrolytic enzyme activation and for vascular damage in the early stages of hemorrhagic pancreatic necrosis.