Association between Cognitive Function and Physical Function, Frailty, and Quality of Life in Older Breast Cancer Survivors.

BACKGROUND: Older cancer survivors in general are at greater risk for cancer-related cognitive impairment (CRCI), yet few studies have explored its association with health outcomes. This study examined the association between subjective and objective measures of cognitive function and physical function, frailty, and quality of life (QoL) among older breast cancer survivors. MATERIALS AND METHODS: Older breast cancer survivors who reported cognitive concerns completed surveys on patient-reported cognitive function, physical function, frailty, and QoL as well as objective tests of visuospatial working memory and sustained attention. Data were analyzed using descriptive statistics and separate linear regression models. RESULTS: A total of 219 female breast cancer survivors completed the study. Perceived cognitive abilities were associated with better physical function, frailty, and QoL (p ≤ 0.001) while cognitive concerns were negatively related with these metrics (p ≤ 0.001). Poorer visuospatial working memory and sustained attention were linked to increased frailty (p ≤ 0.001-0.01), whereas poorer sustained attention was associated with poorer physical function (p < 0.01). CONCLUSIONS: Older breast cancer survivors with perceived cognitive impairment and poorer cognitive performance reported poorer physical functioning, increased frailty, and poorer QoL. These findings underscore the importance of assessing cognitive concerns and their associated outcomes in older breast cancer survivors.

Is routine use of adjuvant chemotherapy for rectal cancer with complete pathological response justified?

BACKGROUND: Patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiation (nCRT) can have a complete pathologic response (pCR), and are given postoperative adjuvant chemotherapy (ACT). METHODS: A prospectively maintained outcomes database was queried for patients who had pCR to nCRT for LARC from 2000 to 2012. Local recurrence and survival were analyzed according to whether patients received ACT. RESULTS: We identified 139 patients and excluded 9 due to lack of follow-up. Mean age was 58.9 ± 11.8 years. 83 patients (63.8%) did not receive ACT (Group A) and 47 (36.2%) did (Group B). Mean follow-up was 5.7 ± 3 and 5.6 ± 3.5 years for Groups A and B respectively (p = 0.51). Groups were comparable in age, gender, tumor differentiation, and clinical staging. There were no differences in oncological outcomes. CONCLUSION: Avoiding routine use of ACT in patients with a pCR may be considered. Further justification of this approach warrants prospective randomized studies.

Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma.

BACKGROUND & AIMS: De novo synthesis of guanosine diphosphate (GDP)-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or tissue specific transplantation antigen P35B [TSTA3]). GMDS deletions and mutations are found in 6%-13% of colorectal cancers; these mostly affect the ascending and transverse colon. We investigated whether a lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. METHODS: FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx-/- mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by enzyme-linked immunosorbent assays to measure cytokine levels; T cells also were collected and analyzed. Fecal samples were analyzed by 16s ribosomal RNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx-/- or control mice (Ly5.2) into irradiated 8-week-old Fx-/- or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). RESULTS: Fx-/- mice developed colitis and serrated-like lesions. The intestinal pathology of Fx-/- mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx-/- mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency altered the composition of the fecal microbiota, reduced mucosal barrier function, and altered epithelial proliferation marked by Ki67. Fx-/- mice receiving control bone marrow cells had intestinal inflammation and dysplasia, and reduced expression of cytokines produced by cytotoxic T cells. Human sessile serrated adenomas and right-sided colorectal tumors with epigenetic loss of MutL homolog 1 (MLH1) had lost or had lower levels of HES1 than other colorectal tumor types or nontumor tissues. CONCLUSIONS: In mice, fucosylation deficiency leads to colitis and adenocarcinoma, loss of Notch activation, and down-regulation of Hes1. HES1 loss correlates with the development of human right-sided colorectal tumors with epigenetic loss of MLH1. These findings indicate that carcinogenesis in a subset of colon cancer is consequent to a molecular mechanism driven by fucosylation deficiency and/or HES1-loss.

Benign and malignant tumors of the rectum and perirectal region.

Although most rectal masses are histologically characterized as adenocarcinomas, the rectum and perirectal region can be affected by a wide variety of tumors and tumor-like conditions that can mimic the symptoms caused by rectal adenocarcinoma, including mucosal or submucosal rectal tumors such as lymphoma, gastrointestinal stromal tumor, leiomyosarcoma, neuroendocrine tumor, hemangioma, and melanoma, as well as tumors of the perirectal region such as developmental cyst, neurogenic tumor, osseous tumor, and other miscellaneous conditions. As a group, tumors of the rectum are considerably different from the group of tumors that arise in the perirectal region: they are most often neoplastic, symptomatic, and malignant, whereas tumors arising in the perirectal region are most commonly congenital, asymptomatic, and benign. Proctoscopy with biopsy is the most important method for the diagnosis of rectal tumors, but this procedure cannot determine the precise intramural extension of a rectal tumor and cannot accurately distinguish submucosal and intramural tumors from extramural tumors. Cross-sectional imaging, especially transrectal ultrasound and magnetic resonance imaging, allows evaluation of the entire bowel wall thickness and the perirectal tissues, helping further characterize these tumors. Recognition of the existence of these masses and their key clinical and imaging features is crucial for clinicians to accurately diagnose and appropriately manage these conditions.