Poor predictive value of lower gastrointestinal alarm features in the diagnosis of colorectal cancer in 1981 patients in secondary care.

BACKGROUND: Clinicians are advised to refer patients with lower gastrointestinal (GI) alarm features for urgent colonoscopy to exclude colorectal cancer (CRC). However, the utility of alarm features is debated. AIM: To assess whether performance of alarm features is improved by using a symptom frequency threshold to trigger referral, or by combining them into composite variables, including minimum age thresholds, as recommended by the National Institute for Health and Care Excellence (NICE). METHODS: We collected data prospectively from 1981 consecutive adults with lower GI symptoms. Assessors were blinded to symptom status. The reference standard to define CRC was histopathological confirmation of adenocarcinoma in biopsy specimens from a malignant-looking colorectal lesion. Controls were patients without CRC. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values were calculated for individual alarm features, as well as combinations of these. RESULTS: In identifying 47 (2.4%) patients with CRC, individual alarm features had sensitivities ranging from 11.1% (family history of CRC) to 66.0% (loose stools), and specificities from 30.5% (loose stools) to 75.6% (family history of CRC). Using higher symptom frequency thresholds improved specificity, but to the detriment of sensitivity. NICE referral criteria also had higher specificities and lower sensitivity, with PPVs above 4.8%. More than 80% of those with CRC met at least one of the NICE referral criteria. CONCLUSIONS: Using higher symptom frequency thresholds for alarm features improved specificity, but sensitivity was low. NICE referral criteria had PPVs above 4.8%, but sensitivities ranged from 2.2% to 32.6%, meaning many cancers would be missed.

The prevalence and outcomes of frailty in older cancer patients: a systematic review.

BACKGROUND: Frailty is a state of vulnerability to poor resolution of homeostasis following a stressor event, such as chemotherapy or cancer surgery. Better knowledge of the epidemiology of frailty could help drive a global cancer care strategy for older people. The aim of this review was to establish the prevalence and outcomes of frailty and pre-frailty in older cancer patients. METHODS: Observational studies that reported data on the prevalence and/or outcomes of frailty in older cancer patients with any stage of solid or haematological malignancy were considered. We searched Medline, CINAHL, Cochrane Library, EMBASE, Web of Science, Allied and Complementary medicine, Psychinfo and ProQuest (1 January 1996 to 30 June 2013). The primary outcomes were prevalence of frailty, treatment-related side-effects, unplanned hospitalization and mortality. Risk of bias was assessed using the Newcastle-Ottawa checklist. RESULTS: Data from 20 studies evaluating 2916 participants are included. The median reported prevalence of frailty and pre-frailty was 42% (range 6%-86%) and 43% (range 13%-79%), respectively. A median of 32% (range 11%-78%) of patients were classified as fit. Frailty was independently associated with increased all-cause mortality [adjusted 5-year hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.36-2.57]. There was evidence of increased risk of postoperative mortality for both frailty (adjusted 30-day HR 2.67, 95% CI 1.08-6.62) and pre-frailty (adjusted HR 2.33, 95% CI 1.20-4.52). Treatment complications were more frequent in those with frailty, including intolerance to cancer treatment (adjusted odds ratio 4.86, 95% CI 2.19-10.78) and postoperative complications (adjusted 30-day HR 3.19, 95% CI 1.68-6.04). CONCLUSIONS: More than half of older cancer patients have pre-frailty or frailty and these patients are at increased risk of chemotherapy intolerance, postoperative complications and mortality. The findings of this review support routine assessment of frailty in older cancer patients to guide treatment decisions, and the development of multidisciplinary geriatric oncology services.

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer.

BACKGROUND: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas. METHODS: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed. RESULTS: Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis. CONCLUSIONS: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR.

MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers.

Defective DNA mismatch repair in human tumors leads to genome-wide instability of microsatellite repeats and a molecular phenotype referred to as microsatellite instability (MSI). MSI has been reported in a variety of cancers and is a consistent feature of tumors from patients with hereditary non-polyposis colorectal cancer. Approximately 20% of cancers of the uterine endometrium, the fifth most common cancer of women world-wide, exhibit MSI. Although the frequency of MSI is higher in endometrial cancers than in any other common malignancy, the genetic basis of MSI in these tumors has remained elusive. We investigated the role that methylation of the MLH1 DNA mismatch repair gene plays in the genesis of MSI in a large series of sporadic endometrial cancers. The MLH1 promoter was methylated in 41 of 53 (77%) MSI-positive cancers investigated. In MSI-negative tumors on the other hand, there was evidence for limited methylation in only one of 11 tumors studied. Immunohistochemical investigation of a subset of the tumors revealed that methylation of the MLH1 promoter in MSI-positive tumors was associated with loss of MLH1 expression. Immunohistochemistry proved that two MSI-positive tumors lacking MLH1 methylation failed to express the MSH2 mismatch repair gene. Both of these cancers came from women who had family and medical histories suggestive of inherited cancer susceptibility. These observations suggest that epigenetic changes in the MLH1 locus account for MSI in most cases of sporadic endometrial cancers and provide additional evidence that the MSH2 gene may contribute substantially to inherited forms of endometrial cancer.

Mapping an endometrial cancer tumor suppressor gene at 10q25 and development of a bacterial clone contig for the consensus deletion interval.

Frequent loss of chromosome 10q sequences in endometrial cancers suggests the involvement of a tumor suppressor gene. Previous loss-of-heterozygosity (LOH)studies have pointed to the 10q25-q26 region as the likely site of a tumor suppressor involved in endometrial tumorigenesis (S. L. Peiffer et al., 1995, Cancer Res. 55: 1922-1926; S. Nagase et al., 1996, Br. J. Cancer 74: 1979-1983; S. Nagase et al.,1997, Cancer Res. 57: 1630-1633). In an attempt to define further the localization of a tumor suppressor gene at 10q25, we screened a panel of 123 endometrioid adenocarcinomas for loss of heterozygosity of 10q25.3 sequences. Forty-three (35%) revealed LOH at one or more loci. The observed patterns of allelic loss define a minimum consensus region of deletion between D10S221 and D10S610. A sequence-ready bacterial clone contig and a long-range restriction map for a 1-Mb interval spanning the deletion region were developed as the first step in experiments directed toward the discovery the 10q25 tumor suppressor.

PTEN mutations in endometrial cancers with 10q LOH: additional evidence for the involvement of multiple tumor suppressors.

OBJECTIVE: The aim of this study was to assess the involvement of PTEN and other putative 10q tumor suppressors in endometrioid-type adenocarcinomas characterized by loss of 10q sequences. METHODS: PCR-based single-stranded conformational variant analysis and sequencing of individual PTEN exons in 34 tumor specimens and their corresponding normal DNA were used. RESULTS: Thirteen of the 34 tumors (38%) revealed a PTEN mutation: 2 frameshift, 3 nonsense, 3 missense, 3 splice site alterations, and 2 homozygous deletions. CONCLUSION: The observation that greater than 60% of endometrial cancers with 10q LOH lack PTEN mutations, in addition to previously reported LOH data, provides evidence for the existence of other tumor suppressors on 10q. Consideration of PTEN mutation status may prove important in deletion mapping studies to locate additional tumor suppressors on the long arm of chromosome 10.

Comparison of the harmonic scissors and endostapler in laparoscopic supracervical hysterectomy.

We conducted a retrospective analysis of 29 consecutive patients undergoing laparoscopic supracervical hysterectomy to compare outcomes using the endostapler (15 women) versus harmonic scissors (14). Both instruments resulted in similar outcomes with regard to operating room time, blood loss, and hospital stay. The harmonic scissors have the advantage of decreasing patient cost compared with the stapler.

Laparoscopic supracervical hysterectomy versus laparoscopic-assisted vaginal hysterectomy.

This retrospective study compared 41 patients, 21 undergoing laparoscopic-assisted hysterectomy (LAVH) and 20 undergoing laparoscopic supracervical hysterectomy (LSH). The groups were comparable in age, weight, and previous abdominal surgeries. Surgical indications were similar with the exception of uterine carcinoma, which was always treated by LAVH. Vaginal repairs were more common in the LAVH group. The mean operative times, estimated blood losses, uterine weights, and hospital stays were all comparable for both groups. A potential advantage of LSH is that it requires less operative dissection of the bladder, ureter, bowel, and uterine artery. The possible disadvantage of LSH is the 10% frequency of cyclic stump bleeding. Larger studies with prolonged follow-up will be necessary to evaluate risks and benefits of the procedures.

Delayed hemolytic transfusion reaction caused by anti-P1 antibody.

A 67-year-old white woman received transfusions of a total of 87 units of whole blood and red blood cells during and within 48 hours following a pneumonectomy. Although she had previously received blood transfusions, unexpected antibodies were not detectable by routine screening. On the second postoperative day, she developed fever, hemoglobinemia, hemoglobinuria, and oliguria. However, the direct antiglobulin test and the antibody screen were negative. On the eighth postoperative day, an IgM anti-P1 antibody was detected for the first time. This anti-P1 antibody increased in thermal amplitude from 22 to 37 C, but remained IgM. The circulating transfused P1-positive cells decreased progressively without evidence of bleeding. Testing of the patient's preoperative blood at 15 C found her serum to be weakly reactive with P1 cells, while her own cells were P2. Thus, an anamnestic response to the P1 antigen is the most likely cause of her delayed hemolytic transfusion reaction.