NCCP breast cancer referral guidelines--are breast cancer patients prioritised?

Following centralisation of breast cancer services, the National Cancer Control Programme (NCCP) introduced referral guidelines indicating which patients require urgent, early and routine review. This study prospectively analysed referrals to a symptomatic breast unit over 3 months to measure Primary Care Physician (GP) uptake of the NCCP referral guidelines, compare triage patterns of GP and consultant breast surgeon and evaluate the efficacy of the guidelines at identifying patients with breast cancer. 1044 consecutive referrals were categorised according to NCCP guidelines. 637 (61%) were referred using the NCCP form. GP referrals correlated well with consultant breast surgeon for patients requiring urgent review (r = 0.71, p < 0.001; Pearson). Patients categorised as "urgent" were more likely to have a breast biopsy compared to those categorised as "routine" (p < 0.0001; Chi2). The overall cancer incidence was 34 (3.3%) and significantly higher in the "urgent" group at 10.5%. NCCP guidelines were 91% sensitive for triaging breast cancer patients into the correct (urgent) category. The NCCP guidelines are accurate and should be considered the gold-standard for referral to the symptomatic breast service. Consideration should be given to a GP-delivered service to patients outside the "urgent" category.     

Interferon-γ and cancer immunoediting

Over the last 12 yr, we have shown that interferony and lymphocytes collaborate to regulate tumor development in mice. Specifically, we found that the immune system not only prevents the growth of primary (carcinogen-induced and spontaneous) and transplanted tumors but also sculpts the immunogenicity of tumors that form. These observations led us to refine the old and controversial “cancer immuno-surveillance” hypothesis of Burnet and Thomas into one that we termed cancer immunoediting that better emphasizes the paradoxical host-protective and tumor-sculpting roles of immunity on developing tumors. Our current work focuses on defining the molecular mechanisms that underlie cancer immunoediting and exploring the implications of this process for cancer immunotherapy.     

Why cancer cells metastasize?

Metastasis is so complicated and well organized that there should be a good reason for it to happen. Here a hypothesis is proposed that metastasis of cancer cells is an abnormal form of migration of native stem/progenitor cells since cancer cells derive from stem/progenitor cells and may inherit stemness, including migration ability. This is an intrinsic potential and external cause mode. During metastasis, cancer cells are involved in the stem/progenitor cell recruitment to meet the need of organism for homeostasis, regeneration and repair, mediated by external signals and using inherent mechanisms but leading to catastrophic results. The “seed and soil” hypothesis can be redefined as that the “soil” is formed under certain circumstances and the “seed” is attracted to its particular “soil”. Cancer cells in the microenviroment mimicking stem cell niche may have superiority in reactivity to metastatic signals. And very few of migrating cancer cells can form metastases. The conditions suitable for metastasis formation are still waiting to be revealed. The hypothesis tries to explain why cancer cells metastasize. It is hoped that the examination of this hypothesis may lead us to the real answer.     

Early manifestations of pancreatic cancer: The effect of cancer–nerve interaction

Clinical manifestation is important for the diagnosis of pancreatic cancer (PanCa). No typical symptoms have been identified that clearly indicate the early stage of PanCa, although most patients with PanCa have symptoms before the cancer is diagnosed. These symptoms are often regarded as common gastrointestinal symptoms and are ignored. The pancreas is richly supplied with nerves, and neuro-cancer interactions begin prior to PanCa cell migration. We hypothesise that the cancer–nerve interaction does generate typical symptoms such as pseudomorphous satiety and mild pain in early PanCa. Constant satiety leads to weight loss. This biological behaviour allows the cancer to progress without attention from the cancer-bearing host. Cancer cells also target the endocrine pancreas, generating a hyperglycaemic state that results in increased energy for cancer cells. The combination of the so-called common gastrointestinal symptoms and diabetes may represent early typical symptoms of PanCa that can be used to improve early diagnosis.     

Do cancer helplines deliver benefits to people affected by cancer? A systematic review

Objectives

To determine the: (1) proportion of studies that describe characteristics of helpline service delivery, compared to the proportion that report trials testing efficacy or effectiveness of helplines in changing user outcomes; (2) proportion of efficacy or effectiveness studies that meet EPOC criteria for methodological rigor; and (3) potential benefits of cancer helplines for people affected by cancer based on findings from rigorous efficacy or effectiveness trials.

Methods

Electronic databases (Medline, PsycINFO, EMBASE and CINAHL) were searched to identify English-language studies describing original research published from 1991 to 2011.

Results

Twenty-eight publications met the review inclusion criteria. From these studies, data on: the characteristics of cancer helpline users; call content; and user satisfaction, were extracted. The potential for helplines to improve the psychosocial outcomes of callers was examined for the three intervention trials.

Conclusion

There is a lack of robust evidence regarding the level and types of benefits that cancer helplines may deliver to callers affected by cancer. Given increased emphasis on delivering best-practise supportive care, building the evidence base in this field may assist cancer helplines to increase their service uptake, reach, and benefit to callers.

Practise implications

There is a need for more rigorous intervention-focussed studies in this field across a broader range of cancer populations. Future studies should focus on relevant patient-centred outcomes, such as improved knowledge and greater involvement in decision-making, while incorporating process measures to account for intervention fidelity and clinical performance.     

Schistosomose urogénitale et cancer

The existence of a link between urinary schistosomiasis (US) and bladder carcinoma was first suspected by C. Goebel in 1905. In 1911, A.R Ferguson, who was a professor of Pathology and Microbiology at the Faculty of Medicine in Cairo, published a more detailed survey from 40 autopsies, and reported a likely association of bladder carcinoma with granulomas caused by US. Subsequently, published results from several studies reinforced Ferguson’s hypothesis. Moreover, in most countries where US was endemic, association of high prevalence of bladder carcinoma with US had been pointed out. A further circumstantial evidence was a higher prevalence of bladder squamous cell carcinoma in areas endemic for SU, whereas urothelial carcinomas were more prevalent in areas which were free of SU. However, evidence of a positive correlation between SU and bladder carcinoma was delivered only many decades later, following the results from case-control studies which were adjusted on age, sex, type of dwelling and tobacco consumption. During SU, the mechanisms underlying the onset of bladder carcinoma are still poorly understood due to the lack of any convenient animal model. Classically, two processes are thought to be involved. Chronic inflammation inside bladder would be caused by granulomas centered by eggs, and would result in a neoplasmic evolution, after years. Moreover, alteration of the bladder dynamics would elicit urine stasis which in turn would cause repeated infection of bacterial or viral origin. Beside the high prevalence of squamous cell type, the natural history of bladder carcinomas caused by SU is similar to that of other malignant tumors of the bladder. Also the treatment and prognosis are identical. Albeit genital involvement is very frequent during SU, Schistosoma haematobium does not appear to be a cause of cancers of genital organs. Schistosoma mansoni and S. japonicum have been suspected to be associated with liver or colic carcinomas, but epidemiological studies have not yielded any firm evidence so far. The entire sequencing of S. haematobium genome, along with the recent availability of a more efficient mouse model, must provide a better understanding of the genesis of bladder carcinomas during SU. However, the key for a sharp decrease in both morbidity and mortality due to SU-linked carcinomas lies in a better control of haematobium schistosomiasis, such as observed in Egypt since 1970.     

Is cancer a transmittable disease?

A direct, horizontal and natural transmission of neoplasic cells has only recently been accepted by the biomedical community. There are three known examples in mammals: the Tasmanian Devil Tumor Disease, the Canine Transmissible Venereal Tumor and a similar disease in Sirian Hamsters. These diseases are not anecdotic cases only, but provide support for the cancer clonal evolution hypothesis.     

Patient–physician colorectal cancer screening discussion content and patients’ use of colorectal cancer screening

Objective

The US Preventive Services Task Force recommends using the 5As (i.e., Assess, Advise, Agree, Assist and Arrange) when discussing preventive services. We evaluate the association of the 5As discussion during primary care office visits with patients’ subsequent colorectal cancer (CRC) screening use.

Methods

Audio-recordings of n = 443 periodic health exams among insured patients aged 50–80 years and due for CRC screening were joined with pre-visit patient surveys and screening use data from an electronic medical record. Association of the 5As with CRC screening was assessed using generalized estimating equations.

Results

93% of patients received a recommendation for screening (Advise) and 53% were screened in the following year. The likelihood of screening increased as the number of 5A steps increased: compared to patients whose visit contained no 5A step, those whose visit contained 1–2 steps (OR = 2.96 [95% CI 1.16, 7.53]) and 3 or more steps (4.98 [95% CI 1.84, 13.44]) were significantly more likely to use screening.

Conclusions

Physician CRC screening recommendations that include recommended 5A steps are associated with increased patient adherence.

Practice implications

A CRC screening recommendation (Advise) that also describes patient eligibility (Assess) and provides help to obtain screening (Assist) may lead to improved adherence to CRC screening.     

5-Aza-2′-deoxycytidine restores the E-cadherin system in E-cadherin-silenced cancer cells and reduces cancer metastasis

Down-regulation of the E-cadherin-mediated cell adhesion system is strongly related to cancer invasion and metastasis. Aberrant CpG hypermethylation in the promoter region of the E-cadherin gene has been shown to be responsible for reduction of E-cadherin expression. The present study was designed to test the hypothesis that the demethylating agent 5-aza-2'-deoxycytidine (AZA) can restore the E-cadherin system and reduce the potential for metastasis. AZA treatment modified the methylation status of the 5' CpG island in the E-cadherin promoter, and induced re-expression of E-cadherin in human cancer cells whose E-cadherin expression had been silenced. The re-expressed E-cadherin was correlated with increased in vitro aggregation and reduced motility. After inoculation of cancer cells (MDA-MB-435S) into the mammary fat pads of mice with severe combined immunodeficiency, the mice were treated for nine consecutive weeks with AZA three times per week i.p. The AZA treatment suppressed both growth of the primary tumor and lung metastasis in comparison with untreated controls, suggesting that the suppression of metastasis may be, at least partly, attributable to restoration of E-cadherin expression. Therefore, inhibition of DNA methylation may be useful for preventing cancer metastasis.     

IκB kinase alpha and cancer

IκB kinase alpha (Ikk-α) gene mutations and IKK-α downregulation have been detected in various human squamous cell carcinomas (SCCs), which are malignancies derived from squamous epithelial cells. These squamous epithelial cells distribute to many organs in the body; however, the epidermis is the only organ mainly composed of stratified squamous epithelial cells, called keratinocytes. SCC is the second most common type of skin cancer. Reducing IKK-α expression promotes tumor initiation, and its loss greatly enhances tumor progression from benign papillomas to malignant carcinomas during chemical skin carcinogenesis in mice. Thus, IKK-α has emerged as a tumor suppressor for SCCs. Furthermore, inducible deletion of IKK-α in the keratinocytes of adult mice causes spontaneous skin papillomas and carcinomas, indicating that IKK-α deletion functions as a tumor initiator as well as a tumor promoter. This article discusses IKK-α biological activities and associated molecular events in skin tumor development, which may provide insight into the diagnosis, treatment, and prevention of human squamous cell carcinomas (SCCs) in the future.     

Aquaporins—new players in cancer biology

The aquaporins (AQPs) are small, integral-membrane proteins that selectively transport water across cell plasma membranes. A subset of AQPs, the aquaglyceroporins, also transport glycerol. AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors. Recent discoveries of AQP involvement in cell migration and proliferation suggest that AQPs play key roles in tumor biology. AQP1 is ubiquitously expressed in tumor vascular endothelium, and AQP1-null mice show defective tumor angiogenesis resulting from impaired endothelial cell migration. AQP-expressing cancer cells show enhanced migration in vitro and greater local tumor invasion, tumor cell extravasation, and metastases in vivo. AQP-dependent cell migration may involve AQP-facilitated water influx into lamellipodia at the front edge of migrating cells. The aquaglyceroporin AQP3, which is found in normal epidermis and becomes upregulated in basal cell carcinoma, facilitates cell proliferation in different cell types. Remarkably, AQP3-null mice are resistant to skin tumorigenesis by a mechanism that may involve reduced tumor cell glycerol metabolism and ATP generation. Together, the data suggest that AQP expression in tumor cells and tumor vessels facilitates tumor growth and spread, suggesting AQP inhibition as a novel antitumor therapy.     

Got a light? Illuminating lung cancer

New mouse models shed light on mechanisms of lung cancer progression and pinpoint Rac1b as a potential therapeutic target (Stallings-Mann et al., this issue).     

What's new in hereditary colorectal cancer?

Precancerous polyposes other than classic familial adenomatous polyposis and the condition hereditary nonpolyposis colorectal cancer, or Lynch syndrome, continue to present major diagnostic challenges for the anatomic pathologist. This editorial highlights the practical significance of novel insights and clinical guidelines in the recent literature, as well as in 4 contributions to this edition of the Archives of Pathology & Laboratory Medicine. The first section will address attenuated familial adenomatous polyposis and a newly recognized type of autosomal-recessive adenomatous polyposis associated with the DNA repair gene MYH. The remainder of the editorial discusses the role of the revised Bethesda guidelines in the diagnosis of hereditary nonpolyposis colorectal cancer and concludes with the recently identified serrated pathway syndrome.     

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer

OBJECTIVES:

The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival.

METHODS:

We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxia-inducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice.

RESULTS:

A significant difference (p = 0.022) in hypoxia-inducible factor 1α expression was observed between non-small cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxia-inducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher''s exact test, p = 0.001) when all types of lung cancer were examined, either collectively or separately.

CONCLUSIONS:

The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.