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The purpose of this study was to determine whether primary breast cancer patients showed evidence of circulating tumour cells (CTCs) during follow-up as an alternative to monitoring disseminated bone marrow tumour cells (DTCs) by immunocytochemistry and reverse transcriptase (RT)–PCR for the detection of micrometastases. We planned to compare CTC and DTC frequency in low-risk and high-risk patients. We identified two cohorts of primary breast cancer patients who were at low (group II, T1N0, n=18) or high (group III, >3 nodes positive (with one exception, a patient with two positive nodes) n=33) risk of relapse who were being followed up after primary treatment. We tested each cohort for CTCs using the CellSearch system on 1–7 occasions and for DTCs by immunocytochemistry and RT–PCR on 1–2 occasions over a period of 2 years. We also examined patients with confirmed metastatic disease (group IV, n=12) and 21 control healthy volunteers for CTCs (group I). All group I samples were negative for CTCs. In contrast, 7 out of 18 (39%) group II primary patients and 23 out of 33 (70%) group III patients were positive for CTCs (P=0.042). If we count only samples with >1 cell as positive: 2 out of 18 (11%) group II patients were positive compared with 10 out of 33 (30%) in group III (P=0.174). In the case of DTCs, 1 out of 13 (8%) group II patients were positive compared with 19 out of 27 (70%) in group III (P<0.001). Only 10 out of 33 (30%) patients in group III showed no evidence of CTCs in all tests over the period of testing, compared with 11 out of 18 (61%) in group II (P=0.033). A significant proportion of poor prognosis primary breast cancer patients (group III) have evidence of CTCs on follow-up. Many also have evidence of DTCs, which are more often found in patients who were lymph node positive. As repeat sampling of peripheral blood is more acceptable to patients, the measurement of CTCs warrants further investigation because it enables blood samples to be taken more frequently, thus possibly enabling clinicians to have prior warning of impending overt metastatic disease.British Journal of Cancer (2009) 100, 160–166. doi:10.1038/sj.bjc.6604773 www.bjcancer.com Published online 25 November 2008 [ABSTRACT FROM AUTHOR]

Sixty-nine cirrhotic patients were treated by injection sclerotherapy for bleeding oesophageal varices, with an emergency hospital mortality, from all causes, of 29%. The treatment of 35 of these continued with elective, long-term injections alone: 9 have so far survived more than 3 years, the longest being 5 years 4 months. The risk factor for rebleeding per patient month was 0·03 and, with its minimal complications, long-term sclerotherapy can be recommended as an alternative to portasystemic shunts for all grades of liver disease. [ABSTRACT FROM PUBLISHER]

Breast cancer micrometastases in axillary lymph nodes have been detected by serial sectioning and immunohistochemistry, and shown to have prognostic significance. We have used polymerase chain reaction (PCR) to see whether we could further improve the detection rate of micrometastases. Fifty-seven axillary lymph nodes from patients with breast cancer were examined histologically to assess the proportion of tumor involvement. Immunohistochemical staining with the use of an anti-keratin 19 antibody confirmed the histological findings. Reverse transcription PCR was then performed on extracted RNA by using K19 primers, and all 18 histologically involved nodes yielded the expected 460-base pair product. Of 39 histologically negative nodes, 4 (10%) gave K19 bands detectable with ethidium staining and a further 10 (28%) gave K19 bands after Southern hybridization. To further increase the detection sensitivity a two stage amplification was performed by using nested primers, and K19 product was found in lymph nodes from patients without cancer, as well as in all the nodes from cancer patients. This was shown to be genuine low level expression from endogenous mRNA template, and not derived from amplification of a K19 pseudogene. Reducing the number of PCR cycles in the two amplification steps did not allow sufficient discrimination between normal nodes and those involved nodes in which K19 expression was only detectable after Southern hybridization. The optimal "cut-off" point to distinguish involved nodes from normal nodes remained at the level of 40 cycles of PCR and Southern hybridization. PCR, using K19 as a tumor marker, has been demonstrated in this study to improve the detection of micrometastases in axillary lymph nodes in patients with breast cancer: sensitivity is limited by the specificity of the tumor marker.

Between 1972 and 1982, 60 patients with histologically proven duct carcinoma in situ (DCIS) without evidence of invasive disease were treated by surgery alone. Treatment was not randomised and was total mastectomy (19), subcutaneous mastectomy (6) or local excision (35). Follow-up was by clinical examination and mammography with a median follow-up of 9 years (range 4-16 years). Twenty-six patients (43%) have recurred locally. The estimated proportion recurrence free at 7 years is 59% (95% CI 46-72%). Local recurrence on the chest wall occurred in one patient having total mastectomy and in the chest wall or nipple in three patients having subcutaneous mastectomy. Twenty-two patients recurred locally in the breast after conservative surgery. The 7-year recurrence-free rates were 94%, 44% and 45% respectively in the three groups. Of those patients who recurred locally 14/26 (54%) did so with invasive disease. Of the 34 who did not develop local recurrence, two developed metastases. The only factor which correlated with local recurrence and invasive local recurrence on multivariate analysis was conservative surgery (hazard ratio 4.71 (1.59-14.0), P = 0.001, and 4.05 (1.00-18.7), P = 0.03, respectively). DCIS can be an aggressive local disease and local excision may be inadequate treatment.

Operations were performed to cannulate the efferent duct of the popliteal node of sheep and, at the same time, the blood vascular system was removed surgically from the popliteal fossa so that the node was deprived of it blood supply. Twelve preparations were technically successful in that lymph flowed spontaneously from the unanaesthetised sheep for from 3 to 30 days after the operation. Eight control preparations were established in which the blood supply of the node with the cannulated efferent duct was left intact. In only four of the test preparations was the function of the node decisively impaired so that dendritic macrophages appeared in the lymph, the output of lymphocytes remained very low, and later histological examination showed the nodes to be grossly depleted of lymphocytes. In two of these four preparations the surgical devascularization of the node was aided by arterial embolization. In the remaining eight test preparations the outputs of lymphocytes in the lymph gradually regained normal values, and the nodes then responded normally to antigenic stimuli.

Individual lymph nodes of sheep were perfused, via a cannula in one of their afferent lymphatics, with a variety of toxic materials. This procedure was designed to ablate the parenchyma of the nodes so that the macrophage-rich afferent lymph would pass unaltered into the efferent duct, which also had been cannulated. Although many materials caused transient inflammation and/or immunoblastic responses, few caused lasting alterations in the cellular composition of the efferent lymph. Only melphalan, an alkylating agent, succeeded in damaging the internal structure of the nodes so that true afferent lymph appeared in the efferent duct and abundant dendritic macrophages could be collected. In the doses necessary to achieve this enough of the melphalan became systematized to produce a transient alopecia.