Relative and disease-free survival for breast cancer in relation to subtype: a population-based study

Purpose

No population-based study has investigated breast cancer (BC) subtypes defined by including Ki67. The aim of this study was to evaluate the relative proportions of immunohistochemical subtypes and differences in relative and disease-free survival between subtypes, in relation to patient and other cancer characteristics in Italian BC patient.

Methods

Information on estrogen, progesterone, human epidermal growth factor (HER2), Ki67, and relapses was obtained for 3,381 cases, sampled randomly and anonymously from cases diagnosed in 2003–2005 in nine Italian cancer registries. Relative excess risks (RERs) of death and risks of relapse 5 years after diagnosis were estimated.

Results

Luminal A cancers were 42 % of the total, luminal B 27 %, luminal-HER2 14 %, triple-negative 11 %, and HER2-enriched 7 %. For non-metastatic (3,302) cases, 4 and 7 % developed locoregional and distant metastases, respectively. RERs of death and risks of relapse were significantly greater for all cancer subtypes than luminal A, particularly for triple-negative and HER2-enriched cancers, which were more frequent in women <40 years.

Conclusions

Our population-based findings confirm that subtype is an independent prognostic factor for BC. Triple-negative and HER2-enriched subtypes would benefit from the development and wide application, respectively, of targeted treatments, which would also improve survival for younger patients.     

Thalidomide-dexamethasone versus Interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study

Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive α-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P  = 0·024) and overall survival (84% vs. 68%; P  = 0·030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm ( P  = 0·014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.     

Severe haemophilia A patients have reduced numbers of peripheral memory B cells

The development of inhibitors is a complication of replacement treatment in Haemophilia. Loss of factor VIII-specific memory B cells in the spleen is associated with down regulation of antibodies in mice treated with high doses of FVIII, but changes in B cell memory have not been described in haemophilic patients. The aim of this study was to evaluate the phenotype of circulating lymphocytes in severe haemophilia A. Twenty patients with inhibitors (PI), 22 without inhibitors (P), nine patients during immune tolerance induction (ITI) treatment and 20 healthy donors (HD) were included. Peripheral blood lymphocytes were examined using flow cytometry. Anti-FVIII antibodies were measured using Bethesda and flow cytometry. Percentages of T subsets and B lymphocytes were similar in all groups. In contrast, memory B cells (CD27+) were decreased in PI and P compared with HD, but the level of significance was higher in PI (P = 0.001) than P (P = 0.01). PI with high level of anti-FVIII antibodies presented the lowest B memory values. CD70 expression was also lowest in PI. Non-switched CD27+ subpopulation (IgD+) was prevalent in PI, but did not show statistical significance. When ITI failed, the percentages of CD27+ B cells after 12 months of ITI were lowest. In a longitudinal study performed in four patients, an increased percentage of CD27+ and CD70+ B cells during ITI was found. This work suggests that different peripheral lymphocyte markers, such as CD27 and CD70 on B cells, may be helpful to evaluate anti-FVIII response and to monitor the success of ITI.     

Perianal disease of tuberculous origin

PURPOSE: A case of anal tuberculosis in an otherwise asymptomatic patient with bleeding anal ulcers is presented. The clinical features of this entity and the problems in differential diagnosis between anal infectious vs. inflammatory diseases are discussed. METHODS: The management and outcome of the case of an adult patient who presented with perianal ulcers is described. RESULTS: On a three-drug antituberculous regimen, symptoms abated, radiographic infiltrates improved, and perianal ulcers healed. CONCLUSION: Anal tuberculosis is an extremely rare disease. A tuberculous origin must be considered when the cause of perianal ulcers is unclear to avoid undesirable delays in the diagnosis and treatment of this disease.     

Prospective randomised clinical trial of single versus double purse-string stapled mucosectomy in the treatment of prolapsed haemorrhoids

Background and aims Despite the excellent results published on circular stapled mucosectomy (CSM), there is still some concern about the application of PPH-33 in the advanced haemorrhoidal disease, where a major prolapse may lead to insufficient resection and ensuing early recurrence. This study is aimed at comparing the outcomes after single purse-string CSM versus double purse-string CSM.Patients and methods A prospective randomised clinical trial of single versus double purse-string CSM for grade III–IV symptomatic haemorrhoids was used. One hundred consecutive patients were randomised to single (group 1, N=50) versus double purse-string CSM (group 2, N=50).Results The mean age was 50.7 years, with a predominance of males (63 vs. 37). Haemorrhoids were classified as grade III in 59% and grade IV in 41% of the patients. Mean follow-up was 26 months. Demographic and clinical features showed no differences between the two groups. The size of the resected doughnut was greater in group 2 (4.95 vs. 3.55 cm; p<0.05), as was the distance of the suture from the dentate line (3.56 vs. 3.16 cm; p<0.05). Early postoperative pain was significantly less in group 2 (linear analogue scale from 0 to 10), 2.08 vs. 3.56 (p<0.001). Postoperative haemorrhage was absent or minimal in 79% of patients. Three patients from group 1 reported persistent pain that was resolved within the first few postoperative months. There were two recurrences in group 1.Conclusion Double purse-string CSM resects a greater doughnut, increases the distance of the staple suture from the dentate line and reduces early postoperative pain in comparison to single purse-string CSM. Larger series are necessary to assert whether recurrence is lower.     

Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma

We present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria. Seventeen (34%) patients achieved CR, 7 (14%) nCR, 5 (10%) VGPR, 15 (30%) PR, and 5 (10%) MR, resulting in an ORR of 98%. Only 1 patient (2%) presented progressive disease. Time to progression (TTP), event-free survival (EFS), and overall survival (OS) projected at 3 years were 60%, 57%, and 74%, respectively, and these parameters were significantly higher in those patients achieving a response of at least VGPR versus those who did not. Grade 3 and 4 nonhematologic adverse events were constipation (10%), fatigue (6%), tremors (4%), mucositis (4%), and palmar-plantar erythrodysesthesia (2%). Grade 3 and 4 neutropenia occurred in 12% of patients. Grade 3 and 4 infections and thromboembolic accidents were observed in 22% and 14% of patients, respectively. In the treatment of elderly patients with newly diagnosed multiple myeloma, ThaDD is a very effective regimen with manageable toxicity.     

Recommendations for the use of sensor‐augmented pumps with predictive low‐glucose suspend features in children: The importance of education

Abstract: Sensor‐augmented pumps, which consist of a pump and a continuous glucose monitoring system, offer considerable therapeutic opportunities, despite requiring close attention in the early phase of their use. The aim of this paper is to provide recommendations on the use of a predictive low glucose management (PLGM) system (Minimed 640G?, Medtronic, Northridge, CA, USA) in adolescents with type 1 diabetes either at the start of therapy or during follow‐up. Sound clinical recommendations on PLGM are of increasing importance since several recent papers have reported significant clinical improvements in patients with PLGM, especially in adults. These recommendations are based on the experience of a group of pediatric endocrinologists who collaborated to closely and intensively study the on‐boarding of adolescent patients with type 1 diabetes on automated systems to gain first‐hand experience and peer‐to‐peer insights in a unique free‐living environment. The suggestions provided here are indicative, so can be adapted to the individual realities and experiences of different diabetes centers. However, we believe that close adherence to the proposed scheme is likely to increase the chances of improving the clinical and metabolic outcomes of patients treated with this therapy.     

Patterns of cervical node metastases from squamous carcinoma of the oropharynx and hypopharynx

A retrospective review of 333 previously untreated patients from 1965 to 1986, with primary squamous cell carcinoma of the oropharynx or hypopharynx, was undertaken to ascertain the prevalence of neck node metastases by neck level. The 333 patients underwent 344 classical radical neck dissections. Patients were grouped by clinical neck status at the time of neck dissection: elective dissection in the N0 neck (N = 71), and immediate therapeutic dissection in the N+ neck (N = 259). Detailed analysis was performed for each group based on the specific primary site. This revealed a predominance of neck node metastases in levels II, III, and IV for both oropharyngeal and hypopharyngeal primaries. Isolated "skip" metastases outside of levels II, III, or IV occurred in only 1 patient (0.3%). Otherwise, level I or V involvement was always associated with nodal metastases at other levels (ie, N2 disease). These data support the trend toward selective limited neck dissection (anterior modified) in N0 patients. Furthermore, they provide the foundation for planning of future prospective trials to assess the efficacy of modifications in the extent of neck dissection for carcinomas of the oropharynx or hypopharynx.     

Incidence of malignant mesothelioma (1980-1999) and asbestos exposure in 190 cases diagnosed among residents of the province of Brescia]

Several cases of malignant mesothelioma (MM) previously unknown to the Occupational Health and Safety Service were recognised in the Province of Brescia after an active surveillance program carried out during the first nineteen years of operation; a large proportion of the cases involved workers occupationally exposed to asbestos. A local Mesothelioma Register was subsequently set up in 1993 and by the end of 1999, 190 MM cases had been collected. The annual incidence ratio (standardized on the Italian population, census 1981, x100,000 person-years) was calculated in the 1980-1999 period and showed an increasing trend for location in the pleura in both sexes; in the 1996-1999 period the incidence ratio was 2.95 for males and 1.35 for females. In the same period, this trend was not observed for peritoneal location, with an incidence ratio of 0.17 and 0.37 for males and females respectively. 161 pleural MM (84.7%) and 28 peritoneal MM (14.7%) are described; histopathologic diagnosis was performed in 161 cases (84.7%). Anamneses were collected for 88% of the cases but with direct information from patients only in 65% of these in the recent period. Only 7 cases of asbestosis were diagnosed in the MM cases, whereas 31 cases of pleural abnormalities were observed but only 17 of these were observed in workers occupationally exposed to asbestos. Occupational asbestos exposure was evaluated as certain, probable or possible in 45% of total cases and in 54% of recently (1996-1999) observed cases, which were ten times more frequent in males. Exposure occurred in sectors works where asbestos was not used as raw material, such as construction, iron and steel and metal working. MM's from environmental and non-occupational exposure to asbestos were very few, 1.5% and 0.5% respectively. In 65 MM's asbestos exposure was unknown (34.2%); 50% of these concerned females; for whom the industry and jobs are discussed. The distribution of histologic types of MM was similar in asbestos exposed and non exposed cases. No association between peritoneal mesotheliomas and heavy exposure to asbestos was observed. Ten cases of MM were diagnosed in subjects under 45 years old (5.2%) with only one case occupationally exposed. 2 cases were exposed to radiation therapy (1%) and 2 cases to thoracic trauma (1%). Although in Italy MM has been included in the list of compensatable occupational diseases by law since 1994, a large number of cases occupationally exposed to asbestos are still not recognised by the National Insurance Institute (INAIL). A number of problems limiting work of the Mesothelioma Register and its usefulness are discussed. The Lombardy Mesothelioma Register set up in January 2000 should be able to overcome the limits identified in the past.     

Antibodies to mycobacterial 65 kDa heat shock protein in systemic sclerosis (scleroderma).

It has been reported that immunity to the 65 kDa heat shock protein of Mycobacterium tuberculosis (MT-hsp65) not only accompanies rheumatoid arthritis (RA), but may also be characteristic of chronic inflammation. We now report serum antibodies to MT-hsp65 in 47% of systemic sclerosis (SSc), 38% of primary Raynaud's phenomenon (PRP) and 5% of systemic lupus erythematosus (SLE). Antibody levels were higher in patients with active or progressive SSc and correlated with the degree of skin fibrosis. Thus, immunity to MT-hsp65 appears in SSc and is not limited to RA. However, it does show some degree of specificity beyond chronic inflammation: PRP patients have a higher reactivity than do SLE patients.