Chemotherapy may eradicate ductal carcinoma in situ (DCIS) but not the associated microcalcifications.

INTRODUCTION: We studied the effect of neoadjuvant chemotherapy (NAC) ± trastuzumab on the ductal carcinoma in situ (DCIS) component in patients with locally advanced breast cancer who achieved pathological complete response (pCR). METHODS: The diagnostic biopsies of 92 consecutive breast cancer patients that were treated with neoadjuvant chemotherapy (NAC) ± trastuzumab were evaluated for the presence of DCIS. Upon completion of NAC, the surgical specimens were evaluated for complete eradication of both the invasive and non-invasive cancer in the breast. The pretreatment mammograms were evaluated for the presence of microcalcifications and compared to the mammograms that were obtained upon completion of therapy prior to surgery. RESULTS: Thirty of 92 patients (33%) had a substantial component of DCIS in the pretreatment biopsy. Thirty nine patients (42%) achieved pCR: 22 (56%) following NAC + trastuzumab, 17 (32%) following chemotherapy only. Ten of 30 patients (33%) with DCIS component achieved pCR: 4 received chemotherapy only, in 6 trastuzumab was added. Multiple microcalcifications on the pretreatment mammograms were observed in 3 of 10 patients with DCIS who achieved pCR. No reduction in the area of calcifications was observed following NAC. CONCLUSIONS: DCIS may be completely eradicated by NAC ± trastuzumab. However, associated microcalcifications probably persist. Patients with locally advanced breast cancer with substantial DCIS may still opt for NAC and breast conservation as the DCIS component may respond and even completely disappear following NAC. Residual widespread microcalcifications after NAC do not necessarily indicate residual cancer. Larger studies are needed to direct the surgical management of these patients.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-11.

BACKGROUND: The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers. OBJECTIVES: To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011. METHODS: Data on patients newly diagnosed with melanoma, SCC and BCC were collected from the MHS Cancer Registry and based on histology reports from the centralized pathology laboratory. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating average annual percentage change (AAPC). RESULTS: During the 6-year study period, 16,079 patients were diagnosed with at least one BCC, 4767 with SCC and 1264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among men and primarily affected the elderly. BCC rates were stable throughout the study period [AAPC -0·7%, 95% confidence interval (CI) -4·5 to 3·2], while the incidence of SCC increased significantly (AAPC 15·5%, 95% CI 2·6-30·0). In contrast, melanoma rates continuously decreased (AAPC -3·0%, 95%CI -4·5 to -0·1). CONCLUSIONS: The incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different aetiologies. These findings underscore the importance of continuous monitoring, education and prevention programmes in a growing high-risk population.

Response of the immune system of mammary tumor-bearing rats to cyclophosphamide and soluble low-molecular mass tumor-associated antigens: the spleen and lymph nodes.

In a previous study, we showed that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed the underlaying mechanisms. Studies were performed on the spleen and lymph nodes from the following groups of mammary tumor-bearing rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, i.v.) rats treated with CPA and sTAA. Different zones of the spleen and lymph nodes were measured and their T cell content (CD4(+) and CD8(+) cells) was analyzed immunohistochemically. CPA decreased the size and cell content of follicles, splenic areas related to the production of B cells, of the marginal zone and to a lesser extent of the periarterial lymph sheath, and decreased the number of CD4(+) and, at a lower rate, of CD8(+ )T cells in the spleen. Addition of sTAA restored activity in the splenic zones producing these cells. Similar effects of CPA and sTAA were found in lymph nodes with accumulation of B lymphocytes in the primary and secondary follicles and of T lymphocytes, including both CD4(+) and CD8(+) cells, in the paracortical zone. We suggest that inhibition of the functional activity of the immune system is one of the main reasons for the toxic effects of chemotherapeutic drugs such as CPA and that the tumor-suppressive antitoxic effects of sTAA result from their activation of B- and T-lymphocyte production in this system, particularly in the spleen and lymph nodes.

Pernicious anemia, gastric carcinoid, and autoimmune thrombocytopenia in a young woman.

The association between gastric carcinoid tumors and pernicious anemia is well recognized. Such tumors occur in the presence of achlorhydria, chronic atrophic gastritis, hypergastrinemia, and enterochromaffin-like cell hyperplasia. In this case report, a 29-year-old woman with pernicious anemia and autoimmune thrombocytopenia who developed gastric carcinoid tumors of the gastric body is described. This is the second description of pernicious anemia associated with autoimmune thrombocytopenia. This association in a young woman together with the therapeutic options and decisions that were taken in the treatment of the patient are discussed.

Renal effects of moderate hypercholesterolaemia in uninephrectomized rats.

Animal studies have shown that a 4-6-fold increase in serum cholesterol aggravates pre-existing renal injury. We studied the renal effects of moderate hypercholesterolaemia over a period of 18 weeks in uninephrectomized rats. Animals were allocated to two groups; the group 1 rats were fed a normal diet, as controls, and the group 2 rats were fed a high cholesterol diet containing 3% cholesterol and 1% sodium cholate by weight. The serum total cholesterol was higher in group 2 than in controls being 2.5 +/- 0.4 vs. 1.0 +/- 0.1 mmol l-1 at 9 weeks and 2.1 +/- 0.3 vs. 1.1 +/- 0.2 mmol l-1 at 18 weeks (p < 0.05 for both). Serum high density lipoprotein cholesterol levels were similar in both groups. The mean systolic blood pressure was higher in group 2 than in controls, at 145 +/- 9 vs. 137 +/- 8 mmHg (p < 0.05) by 13 weeks and 146 +/- 6 vs. 136 +/- 4 mmHg (p < 0.05) at 18 weeks. Serum creatinine and glomerular filtration rates were similar in both groups. Urine protein excretion remained within the normal range in both groups. Histological examination at 18 weeks showed diffuse fatty changes in the liver cells and prominent vacuolization of renal tubule cells in the group 2 rats. Nevertheless, the glomeruli were normal. There was no significant difference in mean glomerular volume between group 2 rats (1.20(-3) +/- 0.09(-3) mm3) and controls (1.36(-3) +/- 0.10(-3) mm3). Thus moderate hypercholesterolaemia for 18 weeks in uninephrectomized rats resulted in a mild elevation in blood pressure, but did not affect glomerular volume or glomerular histology, in spite of the deleterious effects on liver and renal tubule cells. We assume that extremely high levels of serum cholesterol are required to induce glomerulosclerosis in the rat.

Extensive fibrous downgrowth after traumatic corneoscleral wound dehiscence.

Two months after cataract surgery, subconjuctival would gaping developed in our patients as a result of trauma and was resutured. Subsequently, corneal edema and a retrocorneal membrane were noticed. During penetrating keratoplasty, a thick fibrous membrane was found growing from the posterior corneal surface into the anterior and posterior chambers. Histopathologic studies revealed fibrous down-growth from the corneal stroma through a gap in Descemet's layer, forming a retrocorneal membrane.