Epidemiology of dental professional liability.

The aim of this article is to collect data relating to dental professional liability in Italy and provide a common platform for discussions among clinicians, legal medicine practitioners, and experts in law. On the basis of two different dental-legal statistical samples (1,670 reports of legal dental experts and 320 civil court decisions) we analyzed the dental professional liability lawsuit in the areas of distribution of lawsuits among the different dental specialties, recurrence and type of errors, outcome of civil suits, parameters of compensation. Some ideas are also proposed for possible strategies in the management of clinical risk (prevention of errors) and court proceedings.

Postoperative chemotherapy in resected gastric cancer: results of a single center experience.

Gastric cancer remains a major health problem despite its decline in incidence in Western countries. Although radical surgery represents the primary curative option for gastric cancer patients, most of them relapse and die due to their disease despite an R0 resection. At present the routine use of postoperative adjuvant therapy to reduce disease recurrence is still considered an investigational approach. Out of a total of 275 patients (stage IB through IV M0 AJCC/UICC) who underwent surgery for gastric cancer at our Surgery Unit between 1993 and 2001, 156 were eligible for adjuvant chemotherapy, of whom only 52 accepted to undergo this treatment. This group of patients was retrospectively compared with a control group (1:2) and overall survival was assessed using hazard ratio and Kaplan-Meier estimates. Five-year survival was 40% in the chemotherapy group and 37.8% in the group which underwent surgery alone. Indeed, chemotherapy did not reduce the risk of death (HR 0.87, 95% CI = 0.57-1.34, p=0.54). Serosal involvement and the invasion of more than 6 lymph nodes were the main independent prognostic factors identified by multivariate analysis. The current study did not show a clear advantage of chemotherapy over surgery alone. However, our results can help to define strategies for future clinical trials with the use of new regimens based on more effective and less toxic drugs.

Multimodal rehabilitation for faecal incontinence: experience of an Italian centre devoted to faecal disorder rehabilitation.

BACKGROUND: Sphincter exercises and biofeedback therapy have been used to treat faecal incontinence but results have been unpredictable and standards of treatment have not yet been established. The aim of this study was to retrospectively evaluate the effects of a new multimodal rehabilitation model on faecal incontinence. METHODS: All of the rehabilitative procedures are guided by manometric data. Primary study outcome criteria were the determination of changes or deterioration in incontinence, failure to achieve full continence and/or presence of faecal urgency. The clinical outcome was designed according to the Jorge-Wexner incontinence score. RESULTS: Between 1997 and 2001, one hundred forty-nine incontinent patients (85 F and 64 M; age range, 41-73 years; mean age, 60.6 years) underwent multimodal rehabilitation at our outpatient unit. The overall mean incontinence score had significantly improved after treatment ( p<0.001), and 58 patients (38.9%) were symptom free. No patient reported any deterioration in incontinence. Faecal urgency persisted in 23 patients (15.4%). CONCLUSION: In conclusion, multimodal rehabilitation, using manometric study, can modify the incontinence score.

Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer.

BACKGROUND & AIMS: Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer. METHODS: Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay. RESULTS: The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03). CONCLUSIONS: COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.

[Somatostatin receptors in non-endocrine tumours]. / Recettori per la somatostatina in tumori non endocrini.

The study of the antiproliferative action of somatostatin (ss) is important not only to understand the regulation of neuroendocrine tumours that express receptors (sst), but also non-endocrine tumours which express these receptors. We previously demonstrated the presence of sst2 in a wide panel of cell lines from human neuroblastoma. Although hypotheses have been put forward that treatment with ss or its analogs may be beneficial in oncological patients, this does not appear to be the case in neuroblastoma; patients with high sst2 levels (who are therefore sensitive to ss treatment) have per se a relatively positive outcome. Therefore, adjuvant treatment with ss is not necessary. Viceversa, patients with a poor prognosis are essentially characterized by a low expression of sst2 (and therefore are insensitive to a therapy with ss). In these patients adjuvant treatment with ss might be indicated, but would have little chance of success. Although the majority of neuroendocrine tumours expresses sst2, pancreas and prostate cancer express sst1 but not sst2, and are therefore insensitive to octreotide treatment which binds preferentially to sst2. Tumours like colorectal carcinoma and breast cancer also express sst2 in their more favourable forms. However, the concentration of sst2 in colorectal cancer is similar, if not lower than that in the surrounding normal tissue. Therefore, the probability of successful adjuvant therapy with ss is relatively low. In breast cancer, it is possible that sensitivity to estrogens may have a positive influence on the expression of sst2. This might justify clinical trials with ss in breast cancer.

Clinicopathologic characteristics and outcome indicators in node-negative gastric cancer.

BACKGROUND AND OBJECTIVES: The relationship between the number of lymph nodes examined and the outcome in patients with node-negative (N(-)) gastric cancer was studied. We compared N(-) patients to those with nodal involvement (N(+)) to identify clinicopathologic characteristics of N(-) gastric cancer. Finally, we evaluated outcome indicators in this group of patients. METHODS: Of 367 patients, 130 (35.4%) were N(-). These patients were stratified according to the main prognostic variables, to assess differences with N(+) cases. A statistical analysis using the Cox model was performed to estimate outcome indicators. RESULTS: N(-) gastric carcinomas were significantly different from N(+) cases in terms of tumor depth and site, TNM stage, grading, residual disease, and vessel involvement. The overall 5-year survival rate was 72%. It was 82% in those patients with more than 15 nodes retrieved and 59% in the others. Serosal involvement, residual disease, and poor differentiation were independent prognostic factors. CONCLUSIONS: The clinicopathologic factors and outcome of N(-) cases were similar to those of early gastric cancer. At least 15 examined nodes appears to be necessary to define a case as N(-). The prognostic value of D2 lymphadenectomy in N(-) patients suggests a biologic role of micrometastases.

Clinicopathologic findings and results of surgical treatment in cardiac adenocarcinoma.

BACKGROUND AND OBJECTIVES: There is a great deal of controversy regarding the definition, classification, and staging of cardiac adenocarcinoma (CA). Recently, a shift from distal to proximal lesions has been documented in gastric cancer. We have stratified our cases of gastric cancer as CA, distal gastric cancer (DGC), and stump cancer (SC). METHODS: Between 1986 and 1998, 450 patients with gastric cancer were operated on at our institute. The resectability rate was 81.6%. Of 367 patients, 48 were CA, 298 DGC, and 21 SC. These 3 groups were compared in terms of clinicopathologic factors and survival rates. RESULTS: CA was significantly higher in male patients and showed a prevalence of the Lauren intestinal type. Regarding staging parameters, CA showed a higher rate of T3 tumors and of resection line involvement. Five-year survival rates were 23. 2% for CA, 45.0% for DGC, and 17.4% for SC. CONCLUSIONS: A possible cause of the poor outcome of CA is presentation at a more advanced stage. CA was similar to SC as far as epidemiology, pathologic factors, and survival rates.

Correlation between DNA content and p53 deletion in colorectal cancer.

OBJECTIVE: To find out whether tumour DNA content correlates with allelic loss of p53 and other pathological features in primary colorectal carcinomas. DESIGN: Ongoing prospective study. SETTING: University hospital, Italy. SUBJECTS: 128 patients who had undergone radical resections for colorectal carcinoma. INTERVENTIONS: Flow cytometric measurement of tumour DNA content and detection of allelic loss on the short arm of chromosome 17 by Southern blot (restriction fragment length polymorphism) analysis in fresh tumour specimens. MAIN OUTCOME MEASURES: Correlation between DNA ploidy and deletion of p53, as well as between these two genetic events and clinicopathological variables. RESULTS: Interpretable DNA histograms were obtained for 122 tumour specimens. Forty-three tumours (35%) were diploid and 79 (65%) aneuploid. The diploid tumours were significantly more common in the proximal colon (from the caecum to the splenic flexure) than in the distal colon (from the descending colon to the rectum) (p = 0.002). The allelic state on the short arm of chromosome 17 was evaluated in 80 heterozygous patients. Forty-four tumour specimens (55%) showed deletion of 17p. Allelic loss of p53 was significantly more common in the distal and rectal tumours than in the proximal ones (p < 0.0001). Aneuploidy was more common among those tumours which had shown deletion of p53 than in those that had not (p = 0.0008). CONCLUSIONS: DNA aneuploidy was significantly associated with the deletion of the p53 gene. This suggests that the functional loss of p53 may favour the growth and establishment of an aneuploid cell population within tumours. Tumours of the proximal and distal colon differ in their genetic nature.

Marked variation of thymidylate synthase and folylpolyglutamate synthetase gene expression in human colorectal tumors.

Patients with advanced colorectal cancer are currently being treated with 5-fluorouracil (5-FU)-based chemotherapy. A growing number of patients with resectable disease receive adjuvant therapy with 5-FU/levamisole (LEV) or 5-FU/folinic acid (LV). However, many patients still fail on these treatments, due to occurrence of natural or acquired tumor resistance. Among clinically relevant mechanisms of resistance to fluoropyrimidines, increased expression of thymidylate synthase (TS) has been emphasized. Another potentially relevant mechanism involves a decrease in folylpolyglutamate synthetase (FPGS) expression. To establish the value of these genes as prognostic factors and predictors of the outcome of 5-FU-based chemotherapy in colorectal cancer, we measured their expression in colorectal tumors from patients undergoing surgery and postoperative chemotherapy and compared it with that in normal colonic mucosa. This was done by a semi quantitative, nonradioisotopic polymerase chain reaction (PCR) method using beta-actin as an internal standard and expressed as a TS/beta-actin or a FPGS/beta-actin mRNA ratio. In tumor samples from 21 colorectal cancer patients, TS gene expression varied 118-fold. The median TS/beta-actin ratio was, in fact, 41.36 x 10(-3) (range 2.49 x 10(-3) to 294.54 x 10(-3)). Little variation in TS gene expression was observed in corresponding normal colic mucosa; the TS/beta-actin gene ratio was lower (median 26.16 x 10(-3); range 8.49 x 10(-3) to 69.49 x 10(-3)). Among tumor explants from 20 patients, FPGS expression varied over 161-fold. A similar marked variation was also observed in normal colonic mucosal samples (over 185-fold). Overall and disease-free survival data suggest an inverse association between the level of tumor TS and FPGS expression and clinical prognosis. The availability of this sensitive and accurate assay for gene expression should now make it possible to extend these laboratory/clinical correlations to larger populations.

Short-term healing following the use of calcium sulfate as a grafting material for sinus augmentation: a clinical report.

Because of the frequent lack of bone in the posterior maxilla, sinus augmentation has become a commonly practiced treatment modality. Many different materials have been used for augmenting the sinus, and the ideal graft is yet to be found. The present article reports the results of sinuses grafted with calcium sulfate in 2 patients. Bone biopsies were harvested 9 months after the augmentation procedure. In the first patient, 3 titanium threaded-cylinder implants were placed in the grafted area after 9 months, while in the second, 1 acid-etched, screw-shaped titanium implant was placed simultaneously with the graft. Light microscopic evaluation revealed new bone formation with ongoing remodeling and progressive lamellar maturation in the specimens. No remnants of the alloplastic material were detectable in any section, either within the bone or in the medullary tissue. When reevaluated at the uncovering procedure, the implants were radiographically and clinically judged to be osseointegrated. These observations suggest that, when used in the appropriate form and with the proper technique, calcium sulfate is a promising graft material for sinus augmentation, producing adequate quantity and quality of new bone for implant placement.

Pelvic floor dyssynergia and bimodal rehabilitation: results of combined pelviperineal kinesitherapy and biofeedback training.

Dyschezia may be caused by pelvic floor dyssynergia, which takes place when a paradoxical contraction or a failure to relax the pelvic floor muscles occurs during attempts to defecate. The aim of our study was to set up a new bimodal rehabilitation programme for pelvic floor dyssynergia, which combined pelviperineal kinesitherapy and biofeedback, and to evaluate the results of this treatment. Thirty-five patients (age range: 28-64 years; mean age: 42.5 years) from the outpatient unit of the Clinica Chirurgica of the University of Florence, Italy, and an age-matched group of 10 healthy control subjects (age range: 31-59 years; mean age 45.7 years) with normal bowel habits and without any defecatory disorders, were studied. The 35 patients were symptomatic for dyschezia without slow colonic transit and had been diagnosed as being affected by pelvic floor dyssynergia. No evidence of any organic aetiology was present but all demonstrated both manometric and radiological evidence of inappropriate function of the pelvic floor. All of the patients underwent bimodal rehabilitation, using the combined training programme Clinical evaluation, computerized anorectal manometry and defecography were carried out 1 week before and 1 week after a completed course in bimodal rehabilitation. The control group underwent manometric and defecographic examination. Their results were compared with those of the 35 patients before and after training. After the programme, all 35 patients had a very significant increase in stool frequency (P < 0.001), while laxative and enema-induced bowel movements had become significantly less frequent (P < 0.001). After bimodal rehabilitation, computerized anorectal manometry showed some peculiar results. Resting anal canal pressure had increased but not significantly. Pre-programme values that indicated a shorter duration ("exhaustio") of maximal voluntary contraction than found in the controls had returned to normal values. The rectoanal inhibitory reflex (RAIR), with incomplete relaxation, which had been shorter than that of controls, became normal by the end of the rehabilitation. All RAIR parameters were significantly different especially when pre- and post-treatment values were compared (P < 0.001). No differences were found as regards rectal sensation parameters and rectal compliance between those before or after bimodal rehabilitation. Defecographic pretreatment X-ray films showed indentation of the puborectalis and poor anorectal angle (ARA) opening, at evacuation, with trapping barium of at 50%. After pelviperineal kinesitherapy and biofeedback training, the indentation had disappeared and the ARA had become significantly larger (P < 0.001) during evacuation. No differences were found after rehabilitation, when both were compared with those of controls. The pelvic floor descent was also significantly deeper (P < 0.001) than before the start of the programme. The bimodal rehabilitation technique can be considered a useful therapeutic option for functional dyschezia as shown by our clinical evaluations, manometric data and defecographic reports.

Character of the invasive margin in colorectal cancer: does it improve prognostic information of Dukes staging?

PURPOSE: The clinical significance and prognostic value of the histopathologic parameters used in both the Dukes and Jass classifications were evaluated to select those with an independent effect on survival after radical surgery for colorectal cancer. METHODS: The depth of local spread (limited to the bowel wall or extended beyond it), the number of metastatic lymph nodes (none, 1-4, more than 4), the character of the invasive margin (pushing or infiltrating), and the presence or absence of conspicuous peritumoral lymphocytic infiltration were assessed in 235 patients who had undergone radical resection for colorectal cancer. The influence of these variables on survival was studied by univariate and multivariate analysis. RESULTS: No significant difference in survival was found between patients with conspicuous peritumoral infiltrate and those without it; moreover, multivariate analysis failed to show any independent prognostic value for either lymphocytic infiltration or depth of local invasion. However, the character of the invasive margin and the number of metastatic lymph nodes were identified as the only variables with any independent importance on survival. Based on these data, a new prognostic model may be proposed; it uses the character of the infiltrative margin as a discriminating factor among patients within the lymph node-negative (Dukes A and B stages) and lymph node-positive (Dukes C1 and C2 subsets) groups. A good prognosis for Dukes A, B, and C1 patients was associated with pushing tumors; C1 and C2 patients with infiltrating tumors had a poor prognosis. On the whole, the new prognostic model has allowed for the placement of 59.6 percent of our patients into groups that provide a confident prognosis. The clinical outcome of Dukes A and B patients with infiltrating tumors is still uncertain. CONCLUSIONS: The character of the invasive margin is an important prognostic factor in colorectal cancer. The association of this parameter with the traditional Dukes classification may provide additional useful prognostic information and aid in the selection of those patients who could most benefit from adjuvant therapy.

Anterior rectocele and anorectal dysfunction.

The two types of anterior rectocele, "distension" of Type 1 rectocele (T1R) and "displacement" or Type 2 rectocele (T2R), have different anatomical, clinical and therapeutic profiles. The aim of this study was to assess anorectal function in patients with distension or displacement rectocele. Three groups of female patients and one group of healthy female subjects were studied. Both the 10 Group 1 subjects, who had been diagnosed as having T1R, and 10 Group 2 women who had been diagnosed as having T2R, were symptomatic for digital evacuation of the rectum. The 10 Group 3 females had complained of sever idiopathic constipation but had no defecatory disorders. The control group was made up to 10 healthy volunteers. All patients and controls underwent clinical evaluation, colonic transit time (CTT), computerized anorectal manometry (CAM), and defecography. Bowel movements and clinical evaluation were similar for both rectocele groups. In Group 1, CAM detected significantly higher anal pressure (P < 0.05) and more impaired rectoanal inhibitory reflex (RAIR) (P < 0.01) in comparison to the other patients and controls. In Group 2, the lowest anal pressure (P < 0.001) was noted but RAIR was normal. Defecographic results, at rest and during evacuation, showed a significantly (P < 0.001) higher anorectal angle and a more abnormal pelvic floor descent in Group 2 than in the other study groups and controls. Therefore, peculiar anorectal function was present in patients with anterior rectocele. A pelvic floor dyssynergia was noted in the distension rectocele group, while a fall of the pelvic floor was noted in the displacement rectocele group.

Nitric oxide synthase and VIP distribution in enteric nervous system in idiopathic chronic constipation.

Idiopathic chronic constipation has been correlated to neural abnormalities that consist of a reduced number of myenteric plexus neurons and a decreased concentration of VIP-positive nerve fibers within the circular muscle. Recent studies hypothesized the involvement of nitric oxide in motility disorders of the human gut. To date, no information is available on nitric oxide involvement in idiopathic chronic constipation. The density of VIP- and nitric oxide-producing neurons was evaluated by immunocytochemistry using anti-VIP and anti-nitric oxide synthase antibodies in five patients with idiopathic chronic constipation. A low total neuron density was found at the myenteric plexus. The density of VIP-positive neurons was low while that of nitric oxide synthase-positive neurons was high at both plexuses. Our data confirm that idiopathic slow-transit chronic constipation is due to abnormal neurogenic factors. The presence of numerous nitric oxide synthase-positive neurons, all along the colon and at both plexuses, supports the hypothesis that an excessive production of nitric oxide may cause the persistent inhibition of contractions.

[Barrett esophagus. Diagnosis and treatment]. / Esofago di barrett. Diagnosi e terapia.

Columnar epithelial metaplasia of the distal esophagus (i.e. barrett's esophagus) is an acquired condition showing a prevalence of 4%. It is probably due to abnormal reparative processes of the esophageal squamous epithelium after gastroesophageal reflux damage. "Mixed" (both acid and biliary) reflux seems more relevant for the pathogenesis of Barrett's esophagus than acid reflux alone, as shown by recent studies with Bilitec 2000. Its diagnosis is not easy for the "cardiac", "fundic" or "indeterminate" types of columnar metaplasia and needs a close cooperation between the endoscopist and the pathologist. On the contrary, it is less difficult for the "distinctive" type of metaplasia. Barrett's esophagus surveillance represents a major challenge in the perspective of its malignant degeneration (adenocarcinoma risk 350 times greater than in the general population). Therapy of Barrett's esophagus includes drugs and surgical treatment. Among the drugs proton pump inhibitors such as Omeprazole seem, at the moment, the most effective for reflux control, as well as the Nissen-Rossetti operation seems the most widely accepted among the anti-reflux surgical procedures. The novelty concerning Barrett's esophagus therapy is represented by laser photoablation associated with proton pump inhibiting therapy. But the experience with this treatment is still at a preliminary stage. For Barrett's esophagus with severe dysplasia and/or adenocarcinoma and/or squamous cell carcinoma esophagectomy is needed with a different extent and approach, according to the extent of Barrett's esophagus and to the stage and site of the neoplastic changes.

Vasoactive intestinal polypeptide and nitric oxide synthase distribution in the enteric plexuses of the human colon: an histochemical study and quantitative analysis.

UNLABELLED: Vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS) positive innervation patterns were immunohistochemically and statistically evaluated in the human colon. Specimens from the right colon (cecum, ascending and right transverse colon) and left colon (left transverse and descending colon) were obtained surgically, fixed either in paraformaldehyde or in Carnoy's or in Bouin's and paraffin embedded. Sections were stained with hematoxylin-eosin, toluidine blue, cresyl violet, neuron-specific enolase, anti-VIP, and anti-NOS. The same results were obtained regardless of the fixative used. Enolase-positive, VIP-positive, and NOS-positive cells were occasionally found within the circular muscle and interpreted as neurons. VIP-positive nerve fibers were evenly distributed within the circular muscle while NOS-positive ones were lacking in its inner portion. The left colon was richer in neurons than the right colon, at both plexuses. VIP- and NOS-positive neuron densities were higher at the left than at the right colon, whereas at all colonic levels VIP-positive neuron percentages at both plexuses and NOS-positive ones at the myenteric plexus were similar. At the submucous plexus the NOS-positive neuron percentage was lower than that of the VIP-positive one. IN CONCLUSION: (a) the right colon contains a lower number of neurons and of VIP- and NOS-positive ones than the left colon, and (b) VIP- and NOS-positive fibers are differently distributed in the inner and outer portions of the circular muscle.

Effects of portacaval anastomosis on pancreatic islets of the rat.

The pancreatic islets of rats with surgically constructed end-to-side portacaval anastomosis were studied immunocytochemically, morphometrically, and ultrastructurally, and the plasma levels of glucose, insulin, and glucagon determined. The results of the current study show that, four weeks after surgery, hypoglycemia, normal insulinemia, and hyperglucagonemia occur and that these hematologic changes are associated with immunocytochemical and ultrastructural signs of impairment of the secretory activity of islet B cells and normal secretion pattern of the remaining islet cell types. The causes and the meaning of the hematologic and islet cell changes are discussed, and the hypothesis has been drawn that they are primarily related to the functional deterioration of the liver, which follows the diversion of the portal blood in the systemic circulation.