Usefulness of ultrasounds in the management of breast phyllodes tumors.

INTRODUCTION: Breast phyllodes tumors (PT) are uncommon fibroepithelial lesions having potential malignant features. These tumors have characteristic features, like pleomorphism, mitoses and overgrowth of the stroma with possible infiltrative margins. The clinical behaviour could be unpredictable, since the relatively high recurrence rate despite correct surgical strategy. Conventional diagnostic examinations show high sensitivity and specificity, but cannot demonstrate the differences between benign and malignant PT. MRI is not more effective. PATIENTS AND METHODS: Sixteen patients affected by PT have been surgically treated at our Institution. All patients received mammography and ultrasonography (US) as preoperative diagnostic work-up. RESULTS: in 13 patients, US was effective in preoperative diagnosis of PT. Mammography was uneffective in detecting breast lesions in 5 cases, while in 11 cases mammographic findings presented benign features, with a round opacity with moderate tissue density and well-defined wall. CONCLUSION: US remains the most useful diagnostic test in detecting PT. However, there is no test effective in identifying malignat PT. In case of suspicion, fine needle biopsy should be performed.

Sacral neuromodulation for the treatment of fecal incontinence: analysis of cost-effectiveness.

PURPOSE: The cost-effectiveness and budget impact of introducing sacral nerve modulation (SNM) as a treatment for fecal incontinence in Italy were evaluated in a simulation model. METHODS: A decision-analysis model with a Markov submodel was used to represent clinical pathways for treatment of patients with fecal incontinence in a scenario with SNM and a scenario without SNM. Data were obtained from published studies and from an expert panel. Evaluation of resource consumption was conducted from the perspective of the Italian National Health Service, and costs were retrieved from the Italian NHS procedures reimbursement list. The time horizon was 5 years, and a 3% discount rate was applied to costs and outcomes. Effectiveness was measured in symptom-free years and in quality-adjusted life-years (QALYs). Fecal incontinence prevalence data and SNM usage forecasts were used to estimate budget impact over the next 5 years. RESULTS: The incremental cost-effectiveness ratio for introducing SNM was €28,285 per QALY gained for patients with a structurally deficient anal sphincter and €38,662 per QALY gained for patients with intact anal sphincters. If a threshold of €40,000 per QALY gained is set as the level that a decision-maker would regard as cost-effective, the probability that the introduction of SNM will be cost-effective would be 99% for patients with a structurally deficient sphincter and 53% for patients with an intact sphincter. Budget impact analysis showed that introducing SNM would have an estimated budget impact of 0.56% over 5 years on the budget allocated for fecal incontinence treatment. CONCLUSION: Our data show SNM to be an efficient investment with an acceptable incremental cost-effectiveness ratio and a limited impact on the total allocated budget for fecal incontinence.

Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression.

Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular transduction of the signals. In colorectal cancer nm23 protein expression seems related to the progression of the disease. By immunohistochemistry we have studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected by colorectal cancer at initial stage. In 12 cases it resulted elevated and in four the disease recurred. The overexpression was not correlated with other prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at initial stage could be considered at risk for disease recurrence and included in a more frequent follow-up protocol.

Surgery in primary gastric lymphoma: impact on clinical staging and long-term survival.

This study analyzes the value of surgery in the treatment, staging and long-term survival of 17 patients affected with primary gastric lymphoma. In 7 patients the neoplasm was localized to the lower third of the stomach, in three to the middle third, in two to the upper third, while in 5 patients there was involvement of the entire stomach. Patients were classified according to the Ann-Arbor classification. Nine patients were stage Ie, five stage Ile, and three stage IVe. A partial gastrectomy was carried out in ten patients and total gastrectomy in 7. In all cases surgical excision of the gastric lymphoma was performed together with intraoperative staging including bilateral hepatic biopsies, and exploration of all abdominal lymph nodes. Two postoperative deaths occurred among the 7 patients who underwent total gastrectomy but no major complications were observed in the remaining 5 patients. No deaths occurred among the 10 patients who underwent partial gastrectomy, but in one case an acute complication developed. Staging laparotomy permitted the correction of clinical staging, and showed that three cases were understaged and one overstaged. All patients received adjuvant chemio-radiotherapy. All but one patient are currently alive, well and free of disease. Survival was correlated significantly with the stage of the disease and extent of gastric involvement, but there was no correlation between survival, histological grade, and the type of gastrectomy performed.

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.

Correlation between human papillomavirus infection and clinicopathological parameters in anal canal carcinoma.

We evaluated human papillomavirus (HPV) DNA in 17 anal canal tumors and its correlation with symptomatology, tumor extension and prognosis. Five squamous carcinomas and 4 cloacogenic tumors resulted HPV+. Statistical analysis showed no correlation between HPV infection and tumor morphology, lymph node involvement or prognosis, and no significant difference in the duration of symptoms between HPV+ and HPV- patients. HPV are involved in the pathogenesis of the tumors, but are not responsible for an increased neoplastic malignancy. Anoscopy with brushing or biopsy is a suitable screening method to identify HPV.

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.

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.

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.

Relationship of symptom duration and survival in patients with colorectal carcinoma.

An early diagnosis in asymptomatic patients and a prompt treatment lead to an improved survival rate in patients with carcinoma of the colon. Patients with a short symptomatic history of colon cancer do not have a better prognosis than patients with a long history. Between 1978 and 1984 a consecutive series of 571 patients with colorectal cancer were admitted to the First Department of Surgery of the University of Rome. All patients were classified into five groups according to the duration of specific intestinal symptoms. In Group 1 (51 cases) asymptomatic patients were included, or patients with no specific symptoms such as asthenia, anemia, occult fecal blood. In Group 2 there were 129 patients with intestinal symptoms of less than 3 months' duration before treatment. In Group 3 there were 192 patients with symptoms of between 4 and 6 months' duration; 151 patients with symptoms of between 6 and 12 months were included in Group 4, and finally 48 patients who presented with symptoms of more than 1 year were included in Group 5. No relationship was noted between tumor site and duration of symptoms. Similarly, no relationship was noted between the duration of intestinal symptoms and stage and tumor differentiation. On the other hand, asymptomatic patients showed a higher incidence of T1N0M0 stage tumor and a lower percentage of undifferentiated neoplasms. The resectability rate was 79% and it was significantly related to the absence of intestinal symptoms. Follow-up data were available in 454 patients (80%). The overall survival rate was 52.4%. In Group 1 through Group 5 the 5-year survival rate was: 83.7%, 50%, 50%, 46.3%, 46.9%. The results of our study indicate that patients admitted in asymptomatic phase presented less-advanced stage tumors and, thus, best survival rate. On the other hand, from our data the duration of intestinal symptoms is not related to the stage and prognosis of tumors.

Synchronous and metachronous retroperitoneal sarcomas: two case reports.

BACKGROUND: Retroperitoneal sarcomas represent less than 1% of all diagnosed human neoplasias. They are generally malignant and can infiltrate retroperitoneal structures. The value of chemotherapy and radiotherapy are difficult to evaluate and the dominating factor in the outcome is the ability to resect the tumor. A few patients develop distant metastases. Recurrence of sarcoma at the operative site and on peritoneal surfaces is a prominent cause of morbidity and mortality. CASE REPORTS: Here we report two patients who underwent surgery for retroperitoneal sarcoma. In each of them at least two primary retroperitoneal tumors were diagnosed. The neoplasms were histologically different, thus they cannot be considered local recurrence but rather primary tumors. CONCLUSION: This is the first report underlying the synchronous or metachronous presence of different histological subtypes in this neoplastic pathology. In explanation of the occurrence of satellite tumors and multiple primary tumors, a virus-associated etiology or polyclonality of the tumor or pluripotentiality of tumor stem cells should be considered.

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.

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.

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.

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.

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.

[Histological and immunological study of patients with lung and digestive tract tumors. Analysis of T and B lymphocytes from the peripheral blood and from the lymph nodes draining the tumor (author's transl)]. / Studio istologico ed immunologico in soggetti con neoplasie del polmone e dell'apparato digerente. Analisi dei linfociti TeB del sangue periferico e dei linfonodi drenanti il tumore

The nature of the immune response to the tumor cell is complex and has yet to be clearly defined. Although past research has foscused on the cytotoxic effect of T lymphocytes versus tumor cells, it has been shown in animal studies that B lymphocytes may also be implicated. Lymphocytes from patients with respiratory and digestive tract tumors were studied. B and T lymphocytes of peripheral blood and of draining lymph node tumors were studied using the following techniques: E rosettes (marker for T cells); membrane Ig, EAC rosettes, aggregated-Ig (marker for B lymphocytes); PHA and PKW in vitro response of lymphocytes using tritiated thymidine incorporation. It was observed that both groups of patients had normal or depressed B and T populations. PHA response was depressed in the majority of the cases with lung tumor. No difference was observed between lymphocytes from peripheral blood and from lymph node suspensions. As in normal lymph nodes the EAC rosettes were constantly observed in the cortical area of lymph node draining tumors. The immune defect observed in part of these cases is discussed in relation to the local and general immunological factors probably responsible for this defect.

Monodermal highly specialized teratoma of the ovary: a sebaceous gland tumor.

Teratomas are neoplasms that originate in pluripotential cells and contain representations of all three germ layers in a rather mature state. Specialized forms of teratoma with unilateral development of certain tissues, such as struma ovarii, argentaffin tumors, cholesteatoma, primary choriocarcinoma of the ovary, pseudomucinous cystoma and neurogenic cysts are known. In this paper we describe an ovarian teratoma consisting entirely of sebaceous glands.

Two twins with teratoma of the ovary. An unusual association: case report.

Teratomas are neoplasms composed of tissue foreign to the area in which it is found. They are considered to be an acquired neoplastic disease and familial incidence has not been reported. Only one occurrence of teratoma between monozygotic twins has been found in the literature. Here we report the case of two heterozygotic twins with benign cystic teratomas of the ovary as a base for future research for efficacy of an accurate familial follow-up in order to diagnose this neoplasm in early stage and for the molecular understanding of pathogenesis of teratoma.

An unusual location of cloacogenic carcinoma.

A 61 year-old female presented with abdominal pain, rectal bleeding, mucus discharge, tenesmus and constipation. Rectal examination and proctoscopy demonstrated rectal stenosis at 5 cm from the anal verge. Transrectal ultrasonography detected a capsulated lesion as a mesenchymal rectal tumor. Computed tomography and endorectal magnetic resonance detected a mesenchymal lesion in the lower-middle rectal thirds. Serum TPA, GICA, SCC and CYFRA were pathological. At surgery the tumour was fixed to the levator ani muscle with rectal folding. Frozen sections of the levator ani muscle biopsies revealed cloacogenic tumour. Abdominoperineal resection was performed. The rectal lesion was cloacogenic carcinoma at 9 cm from the dentate line (pT4 pN0; Ki67 35%; CD31 181 vessels/mm2). Adjuvant radio-chemotherapy was performed. The patient is alive and disease free at 19 months. Extra-anal cloacogenic tumours are an unusual finding. Perhaps cloacal cells were originally present in the rectal wall, but secondary rectal involvement by cloacal remnant from the levator ani muscle cannot be excluded.