Endoscopic pilonidal sinus treatment: a prospective multicentre trial.

BACKGROUND: Pilonidal disease (PD) is a common inflammatory disease of the gluteal fold, resulting in recurrent acute/chronic infection at the level of the natal cleft. In this study, endoscopic pilonidal sinus treatment (EPSiT), a new endoscopic minimally invasive procedure, was evaluated for its effectiveness in treating PD. METHODS: Two hundred and fifty prospective patients with chronic PD were enrolled in a prospective multicentre study conducted at a secondary and tertiary colorectal surgery centre. The primary end-point of this study was wound healing, and the short-/long-term outcomes such as healing time, morbidity rate and recurrence rate were analysed. The secondary end-point of this study was quality of life (QoL). RESULTS: The complete wound healing rate was 94.8%, and the mean complete wound healing time was 26.7 ± 10.4 days. The incomplete healing rate (5.2%) was significantly related to the number of external openings (P = 0.01). There was no difference in the failure rate when EPSiT was performed as the first-line treatment for PD or when it was used after unsuccessful procedures (P = n.s.). Recurrence occurred in 12 cases (5%). The QoL significantly increased from preoperative levels 15 days after the EPSiT procedure (45.3 vs 7.9; P < 0.0001). CONCLUSIONS: The EPSiT procedure is a safe and effective technique for treating PD. It provides better short- and long-term outcomes than various other techniques that are more invasive. EPSiT is a minimally invasive outpatient procedure, which is associated with a quick recovery and a good QoL outcome.

Correlation between coronary microvascular function and angina status in patients with stable microvascular angina.

BACKGROUND: Classical anti-ischemic drugs are the first-line form of treatment in patients with microvascular angina (MVA), but they often fail to achieve a satisfactory control of angina symptoms. It is unknown whether there is any relation between improvement of angina status and changes in microvascular function induced by classical anti-ischemic drugs in MVA patients. AIM: To assess whether, in MVA patients, the effects of classical anti-ischemic drugs on symptoms and quality of life (QoL) are related to changes in coronary microvascular function. PATIENTS AND METHODS: We studied 51 patients (59±10 years; 15 men) with MVA. Coronary blood flow (CBF) response to adenosine (ADO) and to cold pressor test (CPT), Seattle Angina Questionnaire (SAQ) and EuroQoL scale were assessed at baseline, in pharmacological washout, and after 12 months under anti-ischemic therapy. Patients were divided into 2 groups: (1) Group 1 included patients with no improvement of QoL (EuroQoL score change < 10 points); (2) Group 2 included patients with QoL improvement (increase in EuroQoL score ≥ 10 points). RESULTS: At baseline, the 2 groups were similar in age, gender, cardiovascular risk factors, CBF response to ADO and to CPT, SAQ and EuroQoL scores. At follow-up the 2 groups differed only for beta blockers use (27% vs. 88% in group 1 and 2, respectively; p < 0.001). A significant improvement in SAQ score was observed only in group 2. CBF response to both ADO and CPT showed a similar improvement in the 2 groups. No relation was found between changes in coronary microvascular function and in angina status. CONCLUSIONS: In MVA patients beta-blockers are more effective than other anti-ischemic drugs in improving angina symptoms. The improvement of angina status does not seem to be mediated by changes in coronary microvascular function.

[Micronutrient deficiencies in osteoporosis]. / Carenze di micronutrienti nell'osteoporosi

Osteoporosis is a disease characterized by a progressive reduction of bone mass and a simultaneous deterioration of skeletal microarchitecture leading to a loss of bone strength, resulting in bone fracture as consequence of even very low traumas. Osteoporosis has only recently been accorded growing clinical and pathological importance for its impact on health. This disease, thanks to considerable increases in life expectancy, is becoming more visible and is now treated either as a serious public health issue of socio-economic importance, and as a multifactorial disease. In fact, both in women and men, osteoporosis is often associated with e hypogonadism as well as with individual traits such as genetic constitution, cytokines, sex and race, which represent non-modifiable endogenous risk factors. In addition, modifiable exogenous risk factors related to lifestyle (e.g. smoking, alcohol consumption, diet) can lead to an acceleration in the genesis of osteoporosis. This article is intended to contribute to the knowledge of exogenous risk factors in osteoporosis, with special consideration to the role of micronutrient deficiencies.

Evolution of clinical behaviour in Crohn's disease: predictive factors of penetrating complications.

BACKGROUND AND AIMS: Crohn's disease is a heterogeneous entity. The Vienna Classification defines three different clinical patterns: 'non-stricturing, non-penetrating', 'stricturing' and 'penetrating'. Aim of this study was to assess the change in clinical behaviour over time and to evaluate whether an evolution towards penetrating complications can be predicted. METHODS: A total of 139 patients with non-penetrating behaviour at the time of diagnosis were included. The mean follow-up was 4.84 years (range 1-23.2 years). The clinical behaviour, according to the Vienna Criteria, was assessed at the diagnosis and at the end of follow up. Statistical analysis was performed by means of the Kaplan-Meier method and standard logistic regression analysis. RESULTS: The cumulative probability of a change in clinical behaviour was 22, 38 and 63% at 3, 6 and 12 years, respectively, and the cumulative probability of developing penetrating complications was 22, 33 and 55% at 3, 6 and 12 years, respectively. Young age at diagnosis (<40 years) and a stricturing behaviour are independent risk factors of developing major penetrating complications (internal fistula, mass or abscess): OR=6.0, 95% CI 1.1-30.5; OR=4.0, 95% CI 1.5-10.9, respectively, but not perianal disease. CONCLUSIONS: The behavioural classification of Crohn's disease is a dynamic model in which each status should be considered as not fixed but evolutive. Perianal disease should be considered a distinct pattern of penetrating behaviour.

[Possible animal models of endocrine, immune and reproductive complications of celiac disease]. / Possibili modelli animali delle complicanze endocrine, immunologiche e riproduttive della malattia celiaca.

This paper underlines the need of developing animal models to study the diverse complications of celiac disease (CD). CD is a multifactorial condition requiring both an exogenous element (gluten) and complex genetic factors; moreover, CD is associated to several endocrine, immune and reproductive diseases, whose onset may be influenced by other environmental factors as well. In particular, the intestinal absorption of exogenous factors may be important for the outcome of CD as well as of the associated diabetes and/or thyroiditis. Presently, there are no adequate animal models for the systemic complications of CD; in particular, there are no gene knock-out models. However, models are available as regards either gluten enteropathy, such as Irish Setter and Balb/c e BDF1 mouse strains, and endocrine-immune diseases associated with CD, such as BB rats and NOD mice. A deeper exploitation of the available models could provide important information on the factors modulating intestinal permeability, the pathogenesis of extraintestinal alterations and the interactions between gluten and other metabolic, nutritional and environmental factors. The elaboration of in vivo models requires a sound basis of knowledge at molecular level, as well as the modulation of the metabolic alteration through relevant exogenous factors, first of all the dietary assumption of gluten. Therefore, the availability of experimental models may provide significant advances on the prevention and treatment, allowing a complete analysis of affected organisms as well as the use of pharmacological and/or immune stimuli; more information may be also derived on the possible long-term effects of gluten traces in CD-affected subjects, thus reducing the need for lengthy clinical studies.

Prognostic impact of CD31 antigen expression in anal canal carcinoma.

BACKGROUND/AIMS: CD31 is a platelet endothelial cell adhesion molecule. Thus CD31 immunostaining of vascular endothelial cells can be used to measure degree of angiogenesis. As angiogenesis is necessary for tumor growth and metastasis, microvessels density could be a predictor of prognosis. The purpose of this study was to examine the relationship between CD31 value and standard pathologic parameters and prognosis of anal canal carcinoma. METHODOLOGY: Twenty-four patients with anal canal carcinoma were evaluated. Five-micron sections of formalin-fixed, paraffin-embedded tissue were tested with monoclonal anti-CD31 antibody. CD31 value is considered positive if more than 185 vessels/mm2 were counted. Pearson's chi 2 test was employed to test for association between CD31 value and clinicopathological variables. RESULTS: We found no correlation between CD31 value and histologic type, lymph node involvement, patients age and neoplastic relapse. Significant correlation was found between CD31 score and depth of parietal invasion. CONCLUSIONS: The relapse type could strengthen the hypothesis that increased vascularity promotes neoplastic dissemination. As angiogenesis could be used as prognostic indicator to determine patients who may be at higher risk for relapse, our results warrant further confirmation. Development of markers of angiogenic activity in anal canal carcinoma must be an integral part of proper clinical trials.

Plasma and tissue prolactin detection in colon carcinoma.

Serum concentrations of prolactin, a trophic hormone produced by the pituitary gland, have been shown to be raised in certain group of patients with cancer. Prolactin was detected in 0-20% of the colon cancer by immunohistochemistry and in plasma in 6-53% of the patients. These conflicting results do not support the hypothesis of an ectopic prolactin production by colon carcinoma. The aim of this study was to confirm the reported incidence of hyper-prolactinemia in colorectal cancer and to find further evidence for an ectopic prolactin production by the tumor. Thirty consecutive patients with colon carcinoma were studied. Before surgery all the patients underwent blood sample collection to assay plasma prolactin levels. All patients underwent colectomy. All the neoplastic specimens were tested with antiprolactin antibody. In none of the patients were significantly high preoperative levels of plasma prolactin found. Prolactin immunostaining was not identified in any of the tumor specimens. We could not confirm previous reports of frequent hyperprolactinemia in patients with cancer. This is the first report in which the incidence of both hyperprolactinemia and prolactin positive immunostaining was 0%. Our study was unable to demonstrate the synthesis of prolactin by colorectal cancers. The tumor is unlikely to be the source of hormone production. Our results suggest that circulating prolactin levels cannot be used as prognostic marker in patients with colon cancer.

Analysis of a follow-up program for anal canal carcinoma.

The ideal follow-up program for anal canal cancer remains unclear and controversial. We hereby describe an extensive follow-up program for anal canal carcinoma in order to evaluate which examinations and which diagnostic techniques really had impact on survival and management. We evaluated 25 patients with anal canal carcinoma. Local excision (LE) was performed in 5 patients, radiochemotherapy (RCT) in 13, radiochemotherapy and local excision (RCTE) in 7. Mean follow-up time was 6.3 years (range 20 months-11 years). The follow-up program included clinical examination, serum tumor markers evaluation, transrectal ultrasonography (TRUS), anoscopy with either mucosal or by Tru-cut needle multiple biopsies, standard chest X-ray and hepatic-inguinal ultrasonography, endoanal magnetic resonance imaging and in some cases total-body skeletal scintigraphy. A large multicentered randomized and prospective trial is surely lacking and should be undertaken as soon as possible. Our results suggest that an effective local control, rather than a higher survival is the reachable goal at present for anal canal carcinomas. However, further steps should be made to achieve better results. After this experience we propose a more semplified follow-up protocol which consists in performing only rectal examination, endoscopy, Tru-cut needle biopsies and TRUS for local control and inguinal ultrasound and TC to evidence distant metastases.

Duodenal pancreatic heterotopy diagnosed by magnetic resonance cholangiopancreatography: report of a case.

We describe herein the case of a heterotopic pancreas that caused stenosis in the second portion of the duodenum. A 46-year-old man presented with upper abdominal pain and a 12-month history of intermittent vomiting. There was no history of melena, hematochezia, hematemesis, clay-colored stools, jaundice, or hepatitis and he did not describe any food dyscrasias, although fatty foods and alcohol seemed to make the symptoms worse. No specific medication or change in position relieved the pain. An initial diagnosis of chronic pancreatitis with multiple pseudocysts was made on the basis of elevated serum amylase and lipase levels, and abdominal ultrasonography and computed tomography (CT) findings. Medical treatment with octreotide was given for 8 weeks, but without any marked effect. Double-contrast barium examination and esophagogastroduodenoscopy were not diagnostic. Magnetic resonance (MR) cholangiopancreatography revealed findings indicative of cystic dystrophy of a heterotopic pancreas (CDHP), and an endoscopy supported this diagnosis. A pancreatoduodenectomy was performed and pathological examination confirmed a diagnosis of CDHP. In our opinion, MR cholangiopancreatography is the diagnostic tool of choice when CDHP is suspected.

Magnetic resonance imaging using endoanal coil in anal canal tumors after radiochemotherapy or local excision.

The ideal method for evaluation of anal canal tumors after radiochemotherapy and/or local excision remains controversial. Endoanal magnetic resonance imaging (EMRI) is a new, promising technique. The effectiveness of EMRI is reported in a study of 24 patients. Axial SET1-weighted and TSET2-weighted, sagittal and coronal T2-weighted sequences using Fat-suppression were acquired. In 4 cases, the low signal/noise ratio did not allow a diagnosis. In 6 cases, the lesion was not detected. Parietal hypo-intense thickening was detected in 14 patients, but it was not diagnostic for disease recurrence. In this study, EMRI showed 58.3% sensitivity and 41.6% specificity, thus it was not useful in the follow-up of anal tumors.

nm23-H1 protein expression in anal canal carcinoma: does it correlate with prognosis?

BACKGROUND AND OBJECTIVES: Anatomic extent is not the sole axis of classification of tumors and of tumor patients relevant to treatment planning and estimation of prognosis. This results in the need to demonstrate an improvement in prognostic assessment and choice of therapy achieved by consideration of factors other than TNM. nm23 protein does prevent tumor from metastasizing and may also play a role in the control of growth and development. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma and to evaluate its influence on the outcome of patients after surgery or radiochemotherapy. METHODS: Twenty-two patients affected by anal canal carcinoma were evaluated. Each section was incubated with monoclonal antibody nm23 NDPK-A. Immunostaining was considered positive when at least 10% of the tumor cells were immunostained. RESULTS: nm23 immunoreactivity was detected in 6/22 (27.3%) tumors. No significant association was found between nm23 expression and prognosis. CONCLUSIONS: The mechanisms causing enhanced nm23-H1 expression in anal canal carcinoma are unknown. Although the level and expression were not correlated with prognosis, activation of nm23-H1 gene might be a prerequisite for oncogenesis in this type of tumor, while an alternate possibility is the modification of cellular characteristics in relation to proliferation and/or differentiation as a consequence of oncogenesis.

An unusual late radiotherapy-related complication requiring surgery in anal canal carcinoma.

We herein describe an unusual late radiation-related complication requiring surgery in a 60-year-old male affected by anal epidermoid carcinoma. The patient presented with obstructed defecation and ulcerated perianal lesions. The perianal biopsies were positive for anal squamous carcinoma. Transanal diagnostic investigations could not be performed because of anal stenosis. Computed tomography detected left inguinal lymphadenopathy and a nonhomogeneous presacral mass, infiltrating the rectal wall, the coccyx, and the sacrum. The patient underwent a colostomy, infusion of cisplatin and 5-fluorouracil, and irradiation of the pelvis, perianal region, and inguinal lymph nodes. In June 1997 the patient complained of the onset of continuous pain at the genitalia, and for penis necrosis he underwent penis amputation. The histologic examination was conclusive for postradiotherapy thrombosis. This complication could strengthen the hypothesis of vasculoconnective damage as the origin of long-term effects of radiotherapy. Probably the minimal dose in transit volume could not be achieved. Careful evaluation in choosing the treatment scheme is necessary if different options are available.

Immunohistochemical assessment of Ki-67 as prognostic cellular proliferation marker in anal canal carcinoma.

In order to define new prognostic factors useful for therapeutic decision-making, the Authors conducted a study on anal canal carcinomas in which Ki-67 proliferation index is correlated with pathological variables and clinical outcome. The Ki-67-detectable antigen is expressed in all stages of the cells cycle except G0. Thus, Ki-67 index can measure cell proliferation and it could be considered an indicator of prognosis. Thirty-one patients with anal canal carcinoma were evaluated. The specimens were formalin-fixed, paraffin-embedded and used for immunostaining of Ki-67 antigen. We found a significant correlation between Ki-67 score and depth of invasion and lymph node involvement. No correlation was found between high Ki-67 value and neoplastic relapse. These results suggest that Ki-67 positivity carries different significance in different cancers. Additional studies are required to ascertain whether more aggressive therapeutic procedures should be applied in the subset of patients with a high growth fraction.

Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.

To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.

Human papillomavirus infection and p53 nuclear overexpression in anal canal carcinoma.

The product of HPV E6 and E7 genes is able to inactivate both the p53 and pRb proteins. The aim of this study was to evaluate the correlation among anal HPV infection and nuclear p53 overexpression. The Authors evaluated HPV DNA by PCR and p53 nuclear expression by immunohistochemistry in 12 cloacogenic and 6 squamocellular carcinoma. HPV DNA was detected in 71.4% of the squamocellular tumors and in 57.1% of the cloacogenic tumors. In squamocellular tumors HPV types 31-33 and 16 were found; in cloacogenic tumors type 16 alone was detected. Nuclear accumulation of p53 was found to be associated with the presence of HPV. There was no significant difference in parietal infiltration, lymph nodes involvement and prognosis between HPV+p53+ patients and HPV-p53- patients. Tumor aggressiveness is likely to be enhanced by factors other than HPV infection and p53 overexpression.

Acute promyelocytic leukaemia: epidemiology and risk factors. A report of the GIMEMA Italian archive of adult acute leukaemia. GIMEMA Cooperative Group.

Acute promyelocytic leukaemia (APL) exhibits peculiar epidemiological, clinical, cytogenetic and molecular features, compared to the other acute myeloid leukaemias (AML). Data on epidemiology and occupational risk factors for APL desumed from the GIMEMA archive are reported and compared with those of the other AML. An exploratory case-case study was designed on AML patients from 56 haematology centres in Italy. Overall, 4296 patients older than 15 yr with a new diagnosis of acute leukaemia were recorded between July 1992 and July 1997. Of these, 335 were classified as APL, and 2894 as other AML. The median age of APL patients was 43 compared to 59 yr for the other AML (p < 0.00001). In order to identify peculiar risk factors for APL development, different parameters were compared in the 2 groups. After adjusting by age no significant differences were observed with regard to education, lifetime prevalence of cancer among siblings and previous diseases in the patient's history. Occupational exposure as a possible risk factor for APL showed no increased risk compared to other AML among farmers, builders and leather workers. A significant association was found in electricians (OR=4.4, 95% CI=2.0-9.7) and a weak association was found in wood workers (OR=3.2, 95% CI=0.8-10.8). The proportion of APL with respect to other AML was significantly higher in the north east of Italy compared to the rest of the country (OR=1.7, 95% CI=1.3-2.2). These data confirm the younger age of APL patients compared to the other AML. A possible role of electromagnetic fields is suggested by the higher risk of APL in electrical workers and in the more industrialized areas of the country.

The prevalence of p53 immunoreactivity in anal canal carcinoma.

We examined the relationship between p53 expression and clinicopathologic parameters in anal carcinoma. p53 immunoreactivity was detected in 14/18 (77.7%) tumors. Significant association was found between p53 expression and depth of invasion. There was no significant association between p53 expression and histologic type, lymph node metastasis, age and prognosis. Possibly the genetic pathway to anal carcinoma involving p53 gene overexpression confer aggressive growth pattern, but it does not result in worse prognosis. The absence of correlation between p53 overexpression and prognosis could be explained by tumors negative for mutations having an excess of wild-type p53 protein.

Genetic instability, p53 and nm23 mutation and clinicopathological features in rectal carcinoma.

Defective DNA mismatch repair proteins fail to correct replication errors (RERs). These defects may lead to secondary, mutation of oncogenes and tumor suppressor genes. Microsatellite instability might be a marker of such replication errors. Eighteen rectal tumors were examined to evaluate genetic instability, in sporadic rectal cancer by PCR. RERs were observed in 27.8% of the cases. No significant difference was noticed between RER+ and RER- patients as far as prognosis, clinicopathological features and p53 gene mutation are concerned. The incidence of nm23 gene mutation was the only statistically significant difference between the 2 groups. Three patients with only one altered microsatellite showed advanced tumor and nm23 gene mutation. Two cases with 5 altered microsatellites and nm23 gene mutated are disease-free: in one of them the p53 gene was also mutated. Probably more than one altered microsatellite is necessary to protect from the effects of secondary mutations.

[Transpyloric prolapse of a gastric carcinoma arising from a pedunculated hyperplastic polyp]. / Prolasso transpilorico di carcinoma gastrico insorto su polipo iperplastico peduncolato.

A case of gastric carcinoma developed on a large pedunculated hyperplastic polyp prolapsed into duodenum is reported. The cases of transpyloric prolapsed primary pedunculated gastric carcinoma are rare, only 34 cases have been described in Japan during the past 35 years, including the sessile forms. These gastric polyps should be considered in the differential diagnosis of intraluminar filling defects of the duodenal bulb. Endoscopy and biopsy are essential for a correct diagnostic evaluation. Large hyperplastic polyps, especially if prolapsed, require a surgical excision.

Trans anal full thickness tru-cut needle biopsies in anal canal tumors after conservative treatment.

After conservative treatment anal mucosal biopsies enable exclusion of neoplastic cells only on the endoluminal surface. We used transanal full thickness tru-cut needle biopsies in the follow-up of 11 anal tumors. Full thickness tru-cut needle biopsies showed malignant cells in the fibrous tissue in 3 patients and few cells with atypical nuclear features in another 2. All diagnostic exams resulted negative. Therefore, needle biopsies were helpful to diagnose neoplastic remainder. Multiple samples are necessary to reduce the false negative number. This method is simple, relatively inexpensive, easily repeatable and not burdened with complications.