Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients. PATIENTS AND METHODS: We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery. RESULTS: We identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54-1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40-0.68 P < 0.0001) and overall survival (HR 0.45; 95% CI 0.32-0.64, P < 0.0001). CONCLUSION: The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.

Angiosarcoma and atypical vascular lesions of the breast: diagnostic and prognostic role of MYC gene amplification and protein expression.

MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The differential diagnosis between atypical vascular lesion (AVL) and low-grade angiosarcoma (AS) can be occasionally very difficult or even impossible, and MYC amplification status has been pointed as an important diagnostic tool to distinguish cutaneous vascular lesions of the breast. We assessed MYC amplification and protein expression status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, in 49 patients diagnosed with breast AS, and 30 patients diagnosed with post-radiation AVL of the breast. Clinical and pathological features, and follow-up data were collected, and survival analyses were performed. Among 37 patients with SAS, twenty patients had tumors with high-level MYC amplification and protein overexpression (54 %). None of primary angiosarcomas (PAS) or AVL cases showed MYC amplification or protein expression. Concordance between MYC amplification (FISH) and protein expression (IHC) was 100 % in AVL, PAS, and SAS. Survival analysis of the SAS patients demonstrates that those with MYC amplification had a significantly worse overall survival compared to cases without MYC amplification (P = 0.035). There was a non-significant trend toward a poor disease-free survival between cases with and without MYC amplification (P = 0.155). Our findings show that MYC amplification is a highly specific but poorly sensitive marker for SAS and, therefore, a negative result does not exclude the diagnosis of angiosarcoma. MYC amplification was associated with adverse prognosis, suggesting a prognostic role of MYC amplification status on SAS of the breast.

Clinicopathological and immunohistochemical study of 30 cases of post-radiation atypical vascular lesion of the breast.

Atypical vascular lesions (AVL) that occur in the field of prior radiation therapy for breast carcinoma are placed within the differential diagnosis with low grade angiosarcoma and other benign vascular lesions. Although considered a benign entity, the exact biological behavior of AVLs is not fully established because of the small number of cases reported in the literature. We aim to further characterize these lesions clinically and histopathologically, and to study their behavior. We report a series of 30 patients with AVL of the breast occurring after radiation exposure, diagnosed and treated at the European Institute of Oncology, Italy. Immunohistochemical study was performed in all cases, using CD31, D2-40, CD105, and Ki-67 antibodies. Twenty-seven patients were treated with standard doses of conventional adjuvant radiation therapy for the prior breast carcinoma. Three patients were treated with intraoperative radiotherapy with electrons. The post-radiation latency interval from breast carcinoma to AVL was 48.5 months (ranged from 1 to 146 months). Most of the lesions were classified as lymphatic type (78.6 %) based on D2-40 positivity. No extension into subcutaneous tissue or significant atypia was noted in all cases. Despite the fact that the AVL of our series have shown benign behavior in 93.3 %, one patient developed local recurrence of AVL, and two cases progressed to angiosarcoma at the previous AVL site. Further studies should be conducted to better understand the clinical behavior and to propose additional histopathologic diagnostic criteria to distinguish AVL from low grade angiosarcoma and those AVL with increased risk for malignant progression. Concerning current treatments of AVL, we recommend complete excision with free surgical margins and close follow up.

Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse.

BACKGROUND: The immunohistochemical (IHC) evaluation of estrogen receptor (ER), progesterone receptor (PgR), Ki-67 and HER2 is considered a surrogate means for identifying the molecular subtypes of breast cancer with different prognosis. PATIENTS AND METHODS: We explored patterns of recurrence in 4837 women with breast cancer defined as Luminal B (ER-positive and/or PgR-positive, HER2 positive and/or Ki-67≥14%) by IHC classification. We evaluated four subgroups within the Luminal B subtype according to HER2 expression and PgR status. RESULTS: Patients within the ER+/PgR+/HER2- subgroup presented a 5-year breast cancer-related survival (BCS) of 97% (95% confidence interval (CI), 96-97) and overall survival (OS) of 95% [95% CI, 95-96], the best survivals of the Luminal B subgroups. In the multivariate analysis, the ER+/PgR-/HER2- subgroup was associated with a reduced BCS (HR 1.71; 95%CI, 1.25-2.35) and OS (HR 1.47; 95%CI, 1.10-1.96) when compared with the ER+/PgR+/HER2- subgroup. Also patients within the ER+/PgR-/HER2+ subgroup had a reduced BCS (HR 1.93; 95%CI, 1.32-2.83) and OS (HR 1.62; 95%CI, 1.14-2.30) when compared with ER+/PgR+/HER2- subgroup. On the other hand, no statistically significant differences were found with regard to BCS and OS among patients with ER+/PgR+/HER2+ and patients with ER+/PgR+/HER2- disease. CONCLUSIONS: PgR loss identifies Luminal B breast cancer subgroups at higher risk of relapse and death, both with HER-2-positive and HER-2-negative disease.

Breast cancer subtypes and outcome after local and regional relapse.

BACKGROUND: To evaluate the outcome of breast cancer patients after locoregional recurrence (LRR) according to tumor biological features evaluated at first diagnosis and at the time of recurrence. PATIENTS AND METHODS: We collected information on all consecutive breast cancer patients operated at the European Institute of Oncology between 1994 and 2005. The tumor characteristics and subsequent outcome of patients who experienced LRR were analyzed. RESULTS: Two hundred and seventy nine patients with LRR were identified, 197 and 82 patients with local and regional recurrence respectively. The overall discordance rate between primary cancer and LRR was 9% for estrogen receptor expression, 22% for progesterone receptor and 4% for human epidermal growth factor receptor 2. For patients with regional recurrence, the risk of distant metastasis was significantly higher compared with local relapse in case of late recurrence (hazard ratio [HR] = 2.76; 95% CI 1.31-5.85). Patients with triple-negative breast cancer at LRR experienced a higher risk of subsequent relapse (HR 2.87 [1.67-4.91]) and death (HR 2.00 [1.25-3.19]). CONCLUSION: LRR correlates with a high risk of subsequent events and death in particular in patients with triple-negative subtype.

Outcome of special types of luminal breast cancer.

BACKGROUND: The identification of special types of breast cancer might be of value in assessing prognosis and predicting response to therapy. METHODS: A total of 7372 consecutive patients with immunohistochemically defined luminal invasive breast cancer operated at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence by histological type. Median follow-up was 5.8 years. RESULTS: Tumors from 5707 patients were classified as invasive ductal cancer (IDC) not otherwise specified (NOS), 851 lobular, 338 mixed ductal and lobular, 250 cribriform, 143 mucinous and 83 tubular carcinomas. Compared with IDC NOS disease-free survival (DFS) was significantly longer in patients with cribriform tumors [5-year DFS 97.9% versus 87.4%; hazard ratio (HR) = 0.48; P = 0.015) and in pooled cribriform plus tubular carcinomas (5-year DFS 98.7% versus 87.4%; HR = 0.45; P = 0.005). Mucinous tumors presented similar DFS if compared with IDC (5-year DFS 93 % versus 87.4%; HR = 1.03; P = 0.91). Conversely, DFS was poorer for patients with lobular carcinoma (5-year DFS 86.8% versus 87.4%; HR = 1.27; P = 0.01). CONCLUSIONS: The diagnosis of tubular, cribriform and lobular carcinomas carry distinct prognostic implications. The identification of these special types has a significant utility in luminal breast cancer and should be considered in therapeutic algorithms.

Prognostic value of Ki-67 labeling index in patients with node-negative, triple-negative breast cancer.

The aim of this analysis was to investigate the usefulness of Ki-67 labeling index (LI) for the identification of different prognostic subgroups in primary node-negative, triple negative breast cancer (TNBC) patients. From January 1997 to December 2005, 1,053 patients operated for TNBC were identified through the institutional clinical database. The study was performed in accordance with REMARK criteria. The relationship between Ki-67LI and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were used to model Ki-67LI as a continuous variable. We selected 496 consecutive patients with node-negative TNBC. Median age was 52 years, median Ki-67LI 48% (range 4-95), and median follow up 6 years (range 0.5-13). Total deaths and deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67LI increased with decreasing age (P<0.01), increasing tumor size (P<0.01), and grade (P<0.01). When analyzing Ki-67LI as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67LI up to about 35% and remained flat for higher values (adjusted effect of Ki-67 P=0.049; adjusted nonlinear effect P=0.021). Accordingly, when dividing patients into lower (≤35%) and higher (>35%) Ki-67LI subgroups, the 5-year cumulative incidence of breast-related deaths were 2.3 and 9.0%, respectively, with an adjusted HR(>35 vs ≤35) of 2.3 (95% CI 1.0-5.8, P=0.046). Within the group of patients with node-negative TNBC, Ki-67LI was associated with different prognoses subgroups. Ki-67LI might be useful in the design of trials of risk-adapted adjuvant therapies.

Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial.

BACKGROUND: On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aromatase inhibitors may be more or less important. PATIENTS AND METHODS: Breast International Group 1-98 trial randomized 6182 women among four groups comparing letrozole and tamoxifen with sequences of each agent; 5177 (84%) had centrally confirmed estrogen receptor (ER) positivity. We assessed whether centrally determined ER, progesterone receptor (PgR), human epidermal growth factor receptor 2, and Ki-67 labeling index, alone or in combination with other prognostic features, predicted the magnitude of letrozole effectiveness compared with either sequence or tamoxifen monotherapy. RESULTS: Individually, none of the markers significantly predicted differential treatment effects. Subpopulation treatment effect pattern plot analysis of a composite measure of prognostic risk revealed three patterns. Estimated 5-year disease-free survival for letrozole monotherapy, letrozole→tamoxifen, tamoxifen→letrozole, and tamoxifen monotherapy were 96%, 94%, 93%, and 94%, respectively, for patients at lowest risk; 90%, 91%, 93%, and 86%, respectively, for patients at intermediate risk; and 80%, 76%, 74%, and 69%, respectively, for patients at highest risk. CONCLUSION: A composite measure of risk informs treatment selection better than individual biomarkers and supports the choice of 5 years of letrozole for patients at highest risk for recurrence.

Prognosis in women with small (T1mic,T1a,T1b) node-negative operable breast cancer by immunohistochemically selected subtypes.

Knowledge is limited about prognostic significance of breast cancer subtypes among women with small invasive node-negative breast tumours. We explored patterns of recurrence in 1691 women with pT1mic/T1a/T1b, pN0 and M0 breast cancer according to four immunohistochemically defined tumour subtypes: (i) Luminal A (ER-positive, PgR-positive, HER2-negative and Ki-67 < 14%); (ii) Luminal B (ER-positive and/or PgR-positive, HER2-positive and/or Ki-67 ≥ 14%); (iii) HER2-positive, both endocrine receptors absent; and (iv) Triple Negative. At multivariate analysis, women with the Triple Negative breast cancer subtype had an increased risk of loco-regional relapse (LRR) (Hazards Ratio (HR) 3.58; 95%CI: 1.40-9.13) and breast cancer related events (HR 2.18; 95%CI: 1.04-4.57). Overall, Luminal B subtype was not associated with a statistically significant increased risk of recurrence compared with Luminal A, while patients with Luminal B subtype tumours overexpressing HER2 had a 2 fold risk of reduced breast cancer related survival (BCS), but not an increased risk of LRR and distant metastases. Women with HER2 breast cancer subtype had a statistically significant increased risk of LRR (HR 4.53; 95%CI: 1.56-13.1), distant metastases and reduced BCS (HR 3.22; 95%CI: 1.44-7.18) and overall survival (HR 2.87; 95%CI: 1.05-7.89) when compared with the Luminal A subtype, at multivariate analysis. In conclusion, women with small size, node-negative, breast cancer are at higher risk of relapse if with HER2-positive endocrine receptor absent or Triple Negative disease.

What can the pathologist offer for optimal treatment choice?

The choice of the most appropriate systemic treatment of patients with metastatic breast carcinoma is a multifaceted decision-making process. The role for the pathologist is to provide a definite diagnosis of metastatic breast carcinoma, whenever needed, and especially to assess the biological parameters with prognostic and predictive value. Although the vast majority of breast carcinomas maintain the same biological features both in the primary and in the metastases, some undergo changes that may indicate that a targeted systemic treatment should be stopped or started, be it endocrine or anti-HER2. Unfortunately these tumours cannot be easily identified clinically, and it may be useful to biopsy the metastatic sites for reassessment of the biological characteristic of the tumours. Intra-tumoural heterogeneity and clonal selection due to the therapy could explain changes in biological features during tumour progression, but it should also be taken into account that the available assays for evaluating hormone receptor and HER2 status are not 100% accurate, even in the hands of expert pathologists. To minimize the risk of inducing inappropriate changes in systemic treatments due to false-positive or false-negative results, the pathologists should make all efforts to improve accuracy and reproducibility of the assay procedures.

Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer.

BACKGROUND: There is limited knowledge about prognosis of selected breast cancer subtypes among very young women. PATIENTS AND METHODS: We explored patterns of recurrence by age according to four immunohistochemically defined tumor subtypes: Luminal A and Luminal B (estrogen receptor positive and/or progesterone receptor positive and either human epidermal growth factor receptor 2 (HER2) positive and/or high Ki-67), HER2-positive (and) endocrine receptor absent and Triple Negative, in 2970 premenopausal patients with pT1-3, pN0-3 and M0 breast cancer. RESULTS: Patients <35 years of age (315, 11%) presented a significantly increased risk of recurrence and death [hazards ratio (HR) = 1.65, 95% confidence interval (CI) 1.30-2.10 and HR = 1.78, 95% CI 1.12-2.85, respectively] when compared with older patients (2655, 89%) with similar characteristics of disease. This was true considering patients with Luminal B [HR = 1.62, 95% CI 1.21-2.18 for disease-free survival (DFS) and HR = 2.09, 95% CI 0.96-4.53 for overall survival (OS)] and with Triple Negative (HR = 2.04, 95% CI 1.11-3.72 for DFS and HR = 2.20, 95% CI 1.10-4.41 for OS) breast cancer, observing the highest risk of recurrence in the younger patients with HER2-positive breast cancer (HR = 2.37, 95% CI 1.12-5.02) when compared with older patients. CONCLUSIONS: Very young patients with Triple Negative, Luminal B or HER2-positive breast cancer have a worse prognosis when compared with older patients with similar characteristics of disease.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer.

BACKGROUND: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. PATIENTS AND METHODS: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). RESULTS: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. CONCLUSION: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.

BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.

Clinical and pathological assessment of high-risk ductal and lobular breast lesions: What surgeons must know.

Terminology in pathology is sometimes over-complicated and may be misinterpreted by clinicians facing patients and having difficulty answering questions posed by them. This may especially be true for some breast lesions with an increased risk of malignant transformation, the complex terminology of which reflects attempts to stratify them according to potential risk. On the basis of morphological and molecular features, both ductal and lobular proliferations have been classified and named in different ways by pathologists, and this often makes it difficult for the treating physicians and the patients to fully understand the nature of the lesions and their associated risks. In order to clarify pathology reports, unambiguous and simple terms are needed.

Abdominal CT findings may suggest coeliac disease.

BACKGROUND: Coeliac disease is the most common gastrointestinal immunological disorder in the western countries. Many adult patients present non-specific symptoms and signs of malabsorption such as chronic diarrhoea, anaemia, weight loss and abdominal distention. In non-specific and doubtful conditions, computed tomography is often the first medical examination performed. In a clinical practice, a critical review of computed tomography signs is therefore mandatory. AIMS: To evaluate the abdominal computed tomography findings, which are useful to suggest the presence of coeliac disease in adult patients. PATIENTS AND METHODS: The computed tomography studies of 28 coeliac patients were reviewed, looking for any intestinal and extraintestinal abnormality. The computed tomography findings evaluated were: abnormalities of intestinal fold pattern, bowel dilatation, fluid and air excess, duodenal abnormalities, intestinal intussusception, bowel wall thickening, lymphadenopathy, ascites, intestinal stenosis, mesenteric vascular changes. The abdominal computed tomography of a group of 30 normal subjects was also analysed. RESULTS: Intestinal fold pattern abnormalities were seen in 23/28 patients. Intestinal dilatation was seen in 21/28. Fluid excess in 18/28 and lymphadenopathy was seen in 12/28 patients; engorgement of mesenteric vessels in 7/28. Bowel wall thickening was observed in 6/28 patients and transient intussusception was observed in 6/28 patients. Increased air content within the bowel in 4/28 and ascites in 2/28 patients. Bowel dilatation together with fluid excess was observed in 18/28 patients. None of the above mentioned abnormalities abnormalities were seen in normal subjects. CONCLUSIONS: Data of the present study show that several abdominal computed tomography findings may be seen in coeliac adult patients; these findings should be taken into consideration with a high in level of suspicion by radiologists, to avoid diagnostic delay and unnecessary diagnostic and therapeutic procedures.

Lipid anomaly in a child with partial duplication 3p.

The authors report a case regarding a 7-year-old girl affected by short height, bone growth delay, lipidic alterations (hypercholesterolemia, hypertriglyceridemia and high apolipoprotein B values) and by a partial duplication of the short arm of the third chromosome: 46,XX, dup(3)(p26-pter). This chromosomal alteration appears "de novo", as the parent's karyotypes are normal and none of the patient's next of kin showed evidence of lipidic anomalies. The patient's short height and slight frontal bossing were the only features that could be described as typical of the dup3p syndrome.

Improvement of intestinal metaplasia six month after misoprostol treatment.

PURPOSE: To establish whether misoprostol (a synthetic prostanoid) is effective in improving intestinal metaplasia of dyspeptic patients. PATIENTS: Of the 206 dyspeptic patients without Helicobacter pylori, 18 (7.1%) had histological evidence of intestinal metaplasia (2 presented mild metaplasia, 9 moderate and 7 severe). They were treated with misoprostol 200 mg twice daily for six months and, after stopping the treatment, they all underwent endoscopic control. RESULTS: There was a statistical significant improvement of intestinal metaplasia (p < 0.001) and of the activity of antral gastritis (p = 0.03). There were no significant changes in antral and body specimens during follow-up. DISCUSSION: Though the small number of the patients and the lack of control group, our results suggest that misoprostol allows regression and/or improvement of histological IM (p < 0.001). It has proved to be effective in prevention of both gastric and duodenal ulcers induced by NSAID therapy, probably related largely to replacement of endogenous prostaglandins inhibited by the use of NSAID and it may also exerts its protective effects through inhibition of gastric acid secretion. Moreover, misoprostol showed to increase the rate of gastric blood flow, inducing a mucosal protective effect against the factors damaging gastric mucosa. It has been also documented that misoprostol regulates inflammatory cytokines and prolonged the survival of transplants, reflecting both its immunosuppressive and anti-inflammatory effect. In conclusion, since intestinal metaplasia increases the risk of gastric cancer, the use of misoprostol, in this pathology, would be of some interest.

[Effects of the triple therapy in the eradication of Helicobacter pylori: comparison of 3 different antibiotics]. / Effetti della tripla terapia nell'eradicazione dell'Helicobacter pylori: confronto tra tre diversi antibiotici.

To compare the effectiveness, in eradicating Helicobacter pylori infection, of three different antibiotics in combination with omeprazole and metronidazole, in order to establish which might be best in clinical practice. One hundred twenty three patients with HP-positivity, assessed by CLO-test and histology were studied. They were randomly assigned to the following therapies: clarithromycin (500 mg thrice daily) for 14 days, amoxycillin (twice daily) for 14 days, azithromycin (500 mg once daily) for 6 days, in combination with omeprazole (twice daily for 20 days and once for one month plus metronidazole (500 mg twice days) for 10 days. The eradication rate, among the three groups, was 97%, 80% and 68% respectively (p = 0.009); no statistical differences were remarked also between the group treated with amoxicyllin and that with clarithromycin, and between the group treated with amoxicyllin and that with azithromycin; there was only a statistical difference between the group treated with azithromycin and that with clarithromycin (p = 0.005). The Authors suggest that all the three antibiotics are effective in curing Helicobacter pylori infection and, that, the various use of the three antimicrobials should be evaluated from time to time on the basis of clinical data of the patients.

[Argyrophilic nucleolar organizer regions (AgNORs) as malignancy biomarkers in colorectal neoplasms]. / Studio delle regioni organizzatrici argirofile del nucleolo (AgNORs) nelle neoformazioni colo-rettali quale indice di malignità biologica.

The high incidence of intestinal cancer has aroused strong interest in researching and trying to discover its morphologic precursors. In this contest the study of nucleolar organizing regions could be interesting as prognostic factor for bowel neoplasm and useful for differential diagnosis of intestinal diseases. The Authors report on the results of their study performed on 30 selected samples from 6 different bowel lesions.