Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?

To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.METHODSTumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTScN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.CONCLUSIONOur data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.

BRCA mutation rate and characteristics of prostate tumor in breast and ovarian cancer families:analysis of 6,591 Italian pedigrees

Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mutation rate in families with Pr C associated with breast and/or ovarian cancers;secondary aims were to compare the characteristics of families and BRCA-related Pr C outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test,we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score≥7 Pr Cs,by testing breast or ovarian cases and inferring the mutation in the prostate cases.The characteristics of families and BRCA-related Pr C outcomes were measured using the chi-square(χ^(2))test and Kaplan–Meier methods,respectively.Results:Among 6,591 families,580(8.8%)with a Gleason score≥7 Pr Cs were identified,of which 332(57.2%)met the Modena selection criteria for BRCA testing.Overall,215 breast or ovarian cancer probands(64.8%)were tested,of which 41 resulted positive for BRCA and one for CHEK2 genes(19.5%).No statistically significant differences were found in BRCA-related Pr C prognosis and in the characteristics of families among BRCA1,BRCA2 and non-tested patients.Ten of 23(44%)mutations in the BRCA2 gene fell in the prostate cancer cluster region(PCCR)at the 3′terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and Pr C.A trend toward a worse prognosis has been found in BRCA2 carriers.

Rectal-cancer radiotherapy damages the perineal muscle floor

The interesting contribution of Qin et al.[1]about radiation injury on the rectum deserves to be integrated with observations regarding the equivalent damage to the perineal striated muscles.In approaching this topic,not yet extensively studied,we were interested at first in delineating its basic pathology by histological methods,as already proposed[2,3].For this,we selected from our anatomopathological archive 20 surgical specimens of abdominoperineal resections.In the first group,we enclosed 10 surgical specimens of lower rectal cancers operated on 5-6 weeks after a neoadjuvant radiochemotherapy,consisting of 50 Gy,fractioned in 5 weeks,and associated with a FOLFOX pharmacological treatment.In the second group,we included 5 cases of the same pathology,at a lower stage,and submitted for surgery 10 days after a‘short-term’neoadjuvant radiotherapy of 25 Gy in 5 fractions over 1 week.A third group encompassed 5 surgical specimens of abdominoperineal resection,performed for recurrent anal cancer 1 year after the same radiation treatment of 50 Gy as applied in the first group.From our study,we excluded cases with neoplastic infiltration of the perineal muscles,previous perineal surgery,radiation or trauma,systemic diseases such as diabetes,vasculitis,connective-tissue or musculoskeletal disorders,manifest atherosclerosis,morbid obesity,and poor nutrition.Clearly,the second and third groups were implemented for dose-and timerelated controls,in comparison to the first group.The perineal striated muscles found in the specimens were extensively studied with serial histological sections of 4mm and different staining techniques(Haematoxylin-Eosin,Trichrome Masson,and Mallory Azan).