One hundred and twenty‐one cases of ductal carcinoma in situ , including 26 cases with T1a invasive carcinoma, were reviewed. Seventy‐nine patients (65%) were treated by mastectomy and 42 (35%) had conservative surgery. Ductal carcinoma in situ was classified as well differentiated (11%), intermediately differentiated (22%) or poorly differentiated (67%) according to nuclear morphology and the presence or absence of cell polarization. Poorly differentiated lesions were significantly larger than intermediately and well differentiated lesions ( P =0.03 and P =0.01, respectively) and were significantly associated with the presence of extensive necrosis, marked periductal inflammation and periductal fibrosis ( P <0.0001). Invasive carcinoma was more common in the poorly differentiated group (25% compared with 18% in the intermediate group and 8% in the well differentiated group) but this was not statistically significant. The spectrum of differentiation was similar in symptomatic and mammographically detected ductal carcinoma in situ . Clinical follow‐up was available in 90 patients (median period 45 months in patients who had undergone mastectomy and 23 months in those who had conservative surgery). Two incidences of recurrent local disease were recorded in the mastectomy group: one patient had well differentiated and the other poorly differentiated ductal carcinoma in situ . No local recurrences were observed in the conservative surgery group, possibly reflecting the shorter follow up period. All histological grades of ductal carcinoma in situ have the potential to progress to invasive carcinoma and mastectomy does not guarantee a cure.
A quick and reliable method for the evaluation and classification of two types of tissues is presented. Several chemometric methods were applied to evaluate multivariate data of the tissue samples with respect to the content of trace elements. The content of Pb, Al, Zn, Cd, Cu, Ni and Co was determined in samples of healthy and cancerous tissue obtained from 26 patients. Determination was done at milligram/kilogram level with inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic absorption spectroscopy (AAS) techniques. Contents of trace metals in studied tissues are not normally distributed; however, normal distribution was confirmed for log values. There is a statistically significant difference in the content of Zn, Cd, Cu and Al (p<0.01) and Ni and Co (p<0.05) when healthy tissue is compared to cancerous one. Correlation between contents of trace elements for studied tissues was positive; the highest was found between Zn and Cu. A chemometric methodology seems to be a promising tool for classifications of the tissue samples.
BackgroundRadical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision.MethodsTREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743.FindingsBetween Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months' follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients.InterpretationShort-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules.FundingCancer Research UK.
In recent years new approaches to the histological classification of ductal carcinoma in situ (DCIS) have been developed in an effort to produce a system which is clinically relevant. In general these systems have emphasized the importance of cytological characteristics rather than architectural patterns. This study attempts to test two of these classification systems by comparing the histological grade of the DCIS component, separately assessed according to each system, with the grade of the invasive component in a series of 103 invasive ductal carcinomas. According to the Holland system, the DCIS component was poorly differentiated in 61 %, intermediately differentiated in 37%, and well differentiated in 2%. Using the Van Nuys system the DCIS component was classified as high grade in 59%, non high grade with necrosis in 10%, and non high grade without necrosis in 31%. The invasive component was grade 3 in 48%, grade 2 in 38%, and grade 1 in 14%. The grade of the DCIS component, assessed by each system, was significantly related (P < 0.0001) to the histological grade of the invasive component. Poorly differentiated DCIS was mainly associated with grade 3 invasive carcinoma, intermediately differentiated DCIS with all three grades, and well differentiated DCIS with grade 1 invasive carcinoma only. High grade DCIS was primarily associated with grade 3, non high grade with necrosis with grades 2 and 3, and non high grade without necrosis with grades 1 and 2 invasive carcinoma. There was a strong correlation between the Holland and Van Nuys systems in the identification of poorly differentiated/high grade DCIS lesions. There was less agreement between the two systems in the assessment of lower grade lesions.
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