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Biomedical subjects

C Bottini

Publications and source records attributed to C Bottini.

11 recordsLinked to original sources

The rectal pocket syndrome after stapled mucosectomy.

OBJECTIVE: Stapled rectal mucosectomy (SM) is less painful than manual haemorrhoidectomy but may be followed by unusual complications which may require reinterventions. The aim of the present study was to report on a particular postoperative complication, the rectal pocket syndrome (RPS). METHODS: Six patients, four females and two males, five with severe proctalgia and signs of intermittent sepsis and one with faecal soiling following SM, underwent clinical examination, proctoscopy (n = 5) anal manometry and ultrasound (n = 4) revealing a painful rectal intramucosal pocket with an endoluminal orifice at the level of the suture line. Four of them underwent a reintervention. RESULTS: At surgery, a faecolyth was found to be entrapped in the rectal pocket with an underlying chronic abscess in four patients. The cavity was laid open and curetted in all cases. One of the females needed a fistulotomy of a low intersphincteric track after one year. In none of the others did endorectal pocketing and abscess or prostatitis recur after a mean follow up of 25 months (range 2-60 months). The male patient still had moderate postevacuation pain and prostatitis possibly via a bacterial translocation after two months. Overall, the incidence of the post mucosectomy RPS at our Units was 2.5%. CONCLUSIONS: The RPS can occur after SM, is likely to be due to a failure of either the purse-string or of the staples causing a suture defect leading to an intramural sinus, and may be successfully treated by a transanal lay-open in most cases.

Abscess↗

Complications after stapled hemorrhoidectomy: can they be prevented?

Stapled hemorrhoidectomy (SH), a new approach to the treatment of hemorrhoids, removes a circumferential strip of mucosa about four centimeters above the dentate line. A review of 1,107 patients treated with SH from twelve Italian coloproctological centers has revealed a 15% (164/1,107) complication rate. Immediate complications (first week) were: severe pain in 5.0% of all patients, bleeding (4.2%), thrombosis (2.3%), urinary retention (1.5%), anastomotic dehiscence (0.5%), fissure (0.2%), perineal intramural hematoma (0.1%), and submucosal abscess (0.1%). Bleeding was treated surgically in 24%, with Foley insertion 15%; and by epinephrine infiltration in 2%; 53% of patients with bleeding received no treatment and 6% needed transfusion. One patient with anastomotic dehiscence needed pelvic drainage and colostomy formation. The most common complication after 1 week was recurrence of hemorrhoids in 2.3% of patients, severe pain (1.7%), stenosis (0.8%), fissure (0.6%), bleeding (0.5%), skin tag (0.5%), thrombosis (0.4%), papillary hypertrophy (0.3%) fecal urency (0.2%), staples problems (0.2%), gas flatus and fecal incontinence (0.2%), intramural abscess, partial dehiscence, mucosal septum and intussusception (each <0.1%). Recurrent hemorrhoids were treated by ligation in 40% and by Milligan-Morgan procedure in 32%. All hemorrhoidal thromboses were excised. Anal stenoses were treated by dilatation in 55% and by anoplasty in 45%. Fissure was treated by dilatation in 57%. Most complications (65%) occurred after the surgeon had more than 25 case experiences of stapled hemorrhoidectomy. The most common complication in the first 25 cases of the surgeon's experience was bleeding (48%). Even though SH appears to be promising, we feel that a multicenter randomized study with a long-term follow-up comparing SH and banding is necessary before recommending the procedure. Most complications can be avoided by respecting the rectal wall anatomy in the execution of the procedure.

Adult↗

Which surgical approach for rectocele? A multicentric report from Italian coloproctologists.

The most effective surgical technique for rectocele has not yet been clearly established. A retrospective multicentric study was carried out to compare the long-term results of 3 endorectal techniques (Block, Sarles and stapled) and the perineal levatorplasty, alone and in association, in a series of patients with symptomatic rectocele. From January 1992 to December 1999, 2212 patients with defecation disorders were referred to 5 Italian coloproctology units. An anterior rectocele was clinically diagnosed in 1045 patients and confirmed with defecography. On the basis of clinical and radiological parameters, 317 patients (312 women; mean age, 52.4+/-20.1 years) were selected for surgery. Group 1 consisted of 141 patients (136 women; mean age, 50.4+/-18.8 years) who were submitted to endorectal operations. Group 2 consisted of 126 women (mean age, 52.5+/-19.7 years) who received perineal levatorplasty. Finally, 50 women (mean age, 54.3+/-21.9 years) in Group 3 received endorectal operations associated with perineal levatorplasty. A total of 269 patients were followed postoperatively (mean period, 24.2+/-3.1 months, 27.5+/-5.4 months and, 22.8+/-2.8 months, respectively) with the same questionnaire and clinical examination. Three months after surgery, a defecography examination and anorectal manometry were performed in 136 and 132 patients, respectively. Operative time, hospital stay and time to return to work were significantly higher in Group 3 (p<0.001). There was one death in Group 3 due to severe sepsis. Main postoperative complications were: in Group 1, hemorrhage (7.8%, all Sarles), dehiscence of the endorectal suture (5.0%, all Block), distal rectal stenosis (2.1%, 1 stapled, 2 block), and rectovaginal fistula (1.4%, all Sarles); in Group 2, delayed healing of the perineal wound (16.4%); in Group 3 delayed healing of the perineal wound (22.0%), hemorrhage (6%, all Sarles), dehiscence (4.0%), stenosis (2.0%). 17.3% of patients of Group 2 and 22.5% of Group 3 complained of dyspareunia. Postoperative defecography showed a complete absence of the rectocele in 44.1% of patients and reduction of size in the others, without significant differences among the three groups. Manometric pattern was not significantly modified by surgery. Significant symptoms recurred in 5.9% of the patients in Group 1, 6.4% in Group 2, and 5.0% in Group 3. Perineal levatorplasty did not significantly improve obstructed defecation, as it did not allow to excise the rectal mucosal prolapse, and was followed by an high incidence of delayed healing of the perineal wound and dyspareunia. Sarles procedure achieved better control of mucosal prolapse but carried a higher complication rate compared to the others. The association of the perineal levatorplasty with an endorectal technique required significantly longer operative time, and led to a longer hospital stay and time to return to work. In conclusion, the investigated techniques showed different patterns of postoperative complications: bleeding after Sarles, dehiscence after Block, dyspareunia after perineoplasty and fatal gangrene after stapled, but non of them showed a clear superiority over the others in term of clinical or functional results 2 years after surgery.

Adult↗

Glyceryl trinitrate for chronic anal fissure--healing or headache? Results of a multicenter, randomized, placebo-controled, double-blind trial.

PURPOSE: Internal anal sphincterotomy for treating chronic anal fissure can irreversibly damage anal continence. Reversible chemical sphincterotomy may be achieved by anal application of glyceryl trinitrate ointment (nitric oxide donor), which has been reported to heal the majority of patients with anal fissure by inducing sphincter relaxation and improving anodermal blood flow. This trial aimed to further clarify the role of glyceryl trinitrate in the treatment of chronic anal fissure. METHODS: A total of 132 consecutive patients from nine centers were randomly assigned to receive 0.2 percent glyceryl trinitrate ointment or placebo twice daily for at least four weeks. The severity of pain and maximum anal resting pressure were measured before and after one week of treatment. Anodermal blood flow was measured before and after application of glyceryl trinitrate or placebo in ten patients. RESULTS: The study was completed by 119 patients (59 glyceryl trinitrate and 60 placebo), matched for gender, age, duration of symptoms, duration of treatment, site of fissure, previous attempts to treat, pain score, and maximum anal resting pressure. Twenty-nine patients (49.2 percent) healed after glyceryl trinitrate and 31 patients (51.7 percent) healed after placebo (P = not significant). Pain score fell significantly in both groups, in addition to maximum anal resting pressure. Anodermal blood flow improved significantly in seven patients receiving glyceryl trinitrate, but not in the three receiving placebo. Twenty-three patients (33.8 percent) experienced headache and 4 (5.9 percent), orthostatic hypotension after glyceryl trinitrate. CONCLUSION: This trial fails to demonstrate any superiority of topical 0.2 percent glyceryl trinitrate treatment vs. a placebo, although the effects of glyceryl trinitrate on anodermal blood flow and sphincter pressure are confirmed. This finding, together with the high incidence of side-effects, should discourage the use of this treatment as a substitute for surgery in chronic anal fissure.

Adult↗

Relationship between folate-binding protein expression and cisplatin sensitivity in ovarian carcinoma cell lines.

It has been suggested that sensitivity of ovarian carcinomas to cisplatin is in part related to an endogenous folate deficiency. In this work, we investigated whether overexpression of the folate-binding protein (FBP), a receptor involved in folate transport, might be associated with cisplatin sensitivity. The results obtained on a panel of ten ovarian carcinoma cell lines that overexpress different levels of the FBP showed a statistically significant relationship between FBP overexpression and cisplatin responsiveness, with the most sensitive cell lines expressing higher FBP levels on their membrane than the less sensitive ones. The relationship was observed both in cells growing in standard medium-containing high-folate concentrations (2.3 microM) and in cells adapted to growth in low-folate (20 nM) medium. Analysis of two cisplatin-resistant cell lines derived from the cisplatin-sensitive IGROV1 ovarian carcinoma cell line indicated that resistance was associated with a significant decrease in FBP expression. However, the receptor does not appear to be directly responsible for drug sensitivity per se as different cell lines transfected with FBP cDNA did not become more sensitive to the drug. Together, the data suggest the possible predictive value of FBP in ovarian carcinoma, as higher levels of expression can be indirectly but significantly associated with increased drug sensitivity.

Carrier Proteins↗

Growth of ovarian-carcinoma cell lines at physiological folate concentration: effect on folate-binding protein expression in vitro and in vivo.

Ovarian-carcinoma cell lines (OVCAR3, IGROVI, OVCA432, SW626 and SKOV3), grown in standard medium containing supra-physiological (2.3 microM) folate concentration, display different levels of reactivity with the anti-folate-binding-protein (FBP) monoclonal antibody MOv18, which recognizes the alpha-isoform of the protein. Gel-filtration and absorption experiments indicated that on IGROVI cells this molecule accounts for all folic-acid binding at nanomolar concentrations. The aim of the study was to investigate the effect of extracellular folate levels on cells adapted to grow in medium containing physiological folate concentration (20 nM). By the ternary complex assay, all cell lines showed a marked depletion of intracellular reduced folates, compared with those in standard folate medium. The monitoring of FBP by MOv18 showed on IGROVI cells a transient up-regulation of the protein, whereas on the other cell lines, except SKOV3, no changes were detected. These data suggest that in these cells further over-expression of the molecule cannot generally be induced by lowering the extracellular folate concentration. On SKOV3, Scatchard analysis of 125I-MOv18 binding, as well as the evaluation of total folate binding capacity, showed a 2- to 3-fold stable increase of FBP expression after long-term growth in low-folate medium. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated in these cells a 1.5-fold increase in alpha-FBP mRNA. SKOV3 cells, maintained in vitro in medium containing supraphysiological and physiological (i.e., low-folate) concentrations were injected into nude mice. Weight differences, though not statistically significant, were observed in favour of low-folate-derived tumors. Immunohistochemical and immunochemical analysis of the tumor samples showed that in SKOV3 cells the receptor modulation can also be induced by restoring the physiological folate concentration in vivo.

Animals↗

Double flap technique to reconstruct the anal canal after concurrent surgery for fistulae, abscesses and haemorrhoids.

Benign anorectal conditions, such as abscess, fistulas and haemorrhoids may occur in the same patients, requiring wide excision of the diseased tissues. This may result in a large de-epithelized area of the anal canal, and removal of perianal skin, eventually leading to a stricture. A rectal mucosal advancement sutured to the apex of a skin rotation flap has been successfully used in four patients to partially reconstruct the anal canal and prevent the formation of an anal stenosis. Complex anal fistulas may be associated with haemorrhoids requiring a wide local excision. A large wound with loss of skin and epithelium may result, which is likely to heal causing an anal stricture. After simple open haemorrhoidectomy, three muco-cutaneous bridges are usually left by the surgeon at the end of the operation to prevent a stenosis, but this may be impossible to perform following haemorrhoidectomy and fistulectomy, procedures requiring wider tissue excision. A technique to create a muco-cutaneous bridge despite an extensive surgical wound had been successfully adopted in four patients with long standing multiple anal fistulas, pelvirectal abscess and haemorrhoids.

Abscess↗

Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19.

Folate-binding proteins (FBP), which are molecules relevant in folate metabolism, are overexpressed in ovarian carcinomas, as detected by the monoclonal antibodies (MAb) MOv18 and MOv19, which recognise two different epitopes of the gp38/FBP. In this paper, features of the FBP such as the distribution on normal tissues and the release in biological fluids of normal and tumour origin have been investigated. Immunohistochemical analyses on frozen sections of normal tissues showed the presence of the gp38/FBP on some epithelia. The reactivity of both the MAb on Fallopian tubes was intense and comparable to that observed on ovary carcinoma sections. The kidney, bronchial glands, alveolar epithelium of the lung, oesophagus, stomach, pancreas, breast and thyroid showed different levels of staining. By MOv18/MOv19 double-determinant immunoradiometric assay (DDIRMA), the gp38/FBP was found in soluble form in ascitic fluid, serum and urine of nude mice in which the human ovary carcinoma cell line IGROV1 grew as ascitic carcinomatosis. In human biological fluids, the gp38/FBP was detected in ascites of 60% of ovarian carcinoma patients, and in 29% of those with other carcinomas, but not in patients with non-epithelial tumours or with other non-tumoral pathologies. The mean serum arbitrary units (a.u.)/ml values of ovary carcinoma patients were significantly different to those of healthy donors or patients with endometriosis (P < 0.005 and P < 0.01, respectively), but not when compared to the sera of lung carcinoma patients. In addition, the sensitivity of DDIRMA was poor, since only 24% of the ovary carcinoma patients were positive with this assay. When a restricted number of cases selected for the presence of tumour cells in the ascites was examined, the percentage of DDIRMA-positive sera and ascites rose to 41 and 94%, respectively. In the urine, a strong reactivity was observed in the samples of both normal and tumour origin.

Animals↗

Polarization of the alpha 6 beta 4 integrin in ovarian carcinomas.

By immunizing a BALB/c mouse with a human ovary-carcinoma cell line (IGROV1), grown intraperitoneally in nude mice, a monoclonal antibody (MAb), designated MAR6, was produced and characterized. Immunofluorescence on the immunizing cell line showed a specific labelling by MAR6 at the cell-to-cell contact points. In addition, MAR6 was found to immunoprecipitate the alpha 6 beta 4 integrin complex. Competition tests with MAbs anti-alpha 6, anti-beta 4, anti-beta 1 sub-units demonstrated that the recognized sub-unit is alpha 6. Indirect immunofluorescence on various cell lines gave MAR6 as positive only on alpha 6-positive lines (IGROV1, OVCAR3, SW626, SKOV3, ME4405, Calu3, N592, MDA468, A431 and HT29). Moreover, on IGROV1 and OVCAR3 ovary-carcinoma cells, which normally grow either adhering to the culture flask or forming clumps in suspension in the medium, MAR6 selectively stained the connection points between the cells in clumps, where, in the same position, the presence of the beta 4 sub-unit, laminin and fibronectin was detected. On the contrary, the beta 1 sub-unit was distributed over the whole cell membrane. The same pattern of labelling by these MAbs was observed in 2 cases of ovarian-carcinoma cells present in ascitic fluids obtained from patients. Immunoperoxidase tests performed on cryosections of various normal tissues showed specific reactivity of MAR6 on basal or basolateral membranes of epithelial cells. On cryosections of ovarian tumors, MAR6 reactivity correlated with the degree of tumor differentiation. Indeed, in benign and well-differentiated tumors, a strong basal or basolateral labelling only of cells surrounding the neoplastic nodules was found. On the contrary, on undifferentiated tumors the inner part of the tumor nodules was also progressively labelled, whereas the staining on the border was weak and discontinuous as a result of the alpha 6 sub-unit dispersion on the tumor cell surface.

Antibodies, Monoclonal↗

New grading and scoring for anal incontinence. Evaluation of 335 patients.

A grading system of anal incontinence (AI) is described that takes into account both degree and frequency of symptoms. A, B, and C indicate AI for flatus/mucus, liquid stool, and solid stool, respectively; 1, 2, and 3 indicate occasional, weekly, and daily AI. A scoring system, ranging from 0 (continence) to 6 (severe AI, i.e., daily AI for solid stool or C3) also is reported. Three hundred thirty-five patients have been evaluated by this method in our institution: 30 percent had severe AI, graded as C3; only 9 percent had mild symptoms graded as A. Both males and females could not control diarrhea (Grade B) in 44 percent of cases. Nearly half of the 110 patients who underwent surgery had a C3 incontinence before treatment. Positive results were achieved in 75 percent of cases after surgery: e.g., AI score significantly improved from 4.2 +/- 1.6 to 1.5 +/- 1.9 (P less than 0.001) in those with AI and rectal prolapse. Most of the failures were the patients with idiopathic C3 incontinence. In conclusion, this grading and scoring system allowed a satisfactory assessment of patients' AI before and after treatment. It may also be used to achieve an objective comparison between different series.

Adolescent↗

Conventional antibodies: requirements and methods for their optimization.

Eighteen years after the discovery of monoclonal antibodies (MAbs), the debate as to whether these reagents have fulfilled their promise must now be addressed. When MAbs were studied as tools for diagnosis and therapy, problems arose regarding the reagents themselves and the recognized target antigens. Because most MAbs are of murine origin, they usually evoke an immune response in human patients, which reduces their effectiveness. Moreover, their bulky size and dispersal via the blood prevent most of the injected antibodies from substantially penetrating solid, poorly vascularized tumors. However, MAbs that are adequately selected and manipulated to circumvent these problems have been found to successfully image tumors and to be therapeutically active.

Antibodies, Monoclonal↗