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Damaged mucosal sites seem to be vulnerable to tumor cell implantation. We describe a case of exfoliated tumor cells from a sigmoid colon cancer seeding a long-standing anal fistula. The implications of this finding are reviewed.
The main pancreatic duct in cats possesses a relatively strong barrier to the diffusion of bicarbonate ions (HCO3-). We studied some of the characteristics of this barrier by perfusing the duct with a solution similar in composition to pancreatic juice before and after exposing the duct mucosa to various test agents. The difference in net flux of HCO3- across the duct before and after exposure to the test agent reflected damage to the barrier. The barrier was damaged by infected bile, aspirin (pH 2.3), hydrochloric acid (pH 2.3), ethanol (5 to 10 per cent), and secondary bile acids. It was not damged by sterile bile, aspirin (pH 6.5), and primary bile acids. These data indicate that the barrier to back diffusion in the pancreatic duct has unique properties, different in some respects from the properties of the gastric mucosal barrier. Furthermore, the barrier is vulnerable to some agents thought possibly to have a role in the pathogenesis of pancreatitis and pancreatic cancer.
The way in which patients cope with cancer throughout the course of treatment and illness can be demonstrated by correlating levels and types of vulnerability with different psychosocial phases. The concept of psychosocial phasing is a hypothesis, the aim of which is to integrate typical problems, concerns, and distress with clinical staging, treatment, and disease progression. Expectations differ at each phase. Accordingly, different problems may arise which clinicians can anticipate and relieve through appropriate interventions.
Undernourished mothers are likely to have limited fat reserves to draw on during lactation. In order to supply nutrition to her child the mother may therefore become more malnourished and suffer from bone resorption. Repeated or overlapping pregnancies with lactation are likely to compound the issue. Little research has been carried out into the health of mothers while breast feeding, or subsequently. There are theoretical reasons to think that the malnourished mother in the developing world may be particularly vulnerable, but no studies appear to have been undertaken. Investigations in the developed world have concentrated on cancers of the reproductive organs and shown consistent evidence in large case-control studies for a reduced risk of pre-menopausal breast cancer in mothers with a history of prolonged breast feeding. In contrast there have been a number of studies in the developed world concerned with emotional well-being with some indications that mothers who breast feed are more likely to be depressed and are less likely to be positive about their baby.
Melanoma may cluster in families with 'family cancer syndromes' in which there is a predisposition to a variety of different tumours. Other families seem vulnerable to melanoma alone. In the majority of these families, the propensity to melanoma is associated with the presence of abnormal melanocytic naevi, the so-called atypical mole syndrome (AMS) phenotype. However, in a smaller number of families, individuals are susceptible to melanoma but have normal naevi. There appears, therefore, to be clinical (and probably genetic) heterogeneity. Segregation analysis does not support a predisposition by single dominant gene as an explanation for the AMS/melanoma syndrome. To date, a single gene which is clearly important for susceptibility to melanoma has not been identified. Karyotypic studies of melanoma tumours have pointed to chromosomes 1, 6, 7, 9 and 10 as possible sites for melanoma related genes. Loss of heterozygosity studies have suggested that chromosome 9 may carry a tumour suppressor gene important in familial disease, and linkage studies appear to confirm this. It is not yet clear, however, what percentage of familial melanoma is attributable to this gene. A more longstanding suggestion that a gene on chromosome 1 may be important has not been confirmed, but a chromosome/gene may be responsible for susceptibility in a small subset of melanoma families. Even within AMS families, there is a lack of concordance between the AMS phenotype and susceptibility to melanoma. This might be explained either by the effects of modifying genes, or the environment.
OBJECTIVE: Children with cancer often develop febrile illnesses after cytotoxic chemotherapy. Determining which children have serious bacterial infections in this vulnerable period would be valuable. We evaluated the ability of a rapid and sensitive assay for the concentration of calcitonin precursors (CTpr) as a sensitive diagnostic marker for bacterial sepsis in febrile, neutropenic children and determined the utility of measuring cytokines to improve the predictive value of this approach. DESIGN: Prospective cohort study. SETTING: Academic children's hospital. PATIENTS: Fifty-six children (aged 5 months to 17 yrs) with a known malignancy who presented with fever and neutropenia. INTERVENTIONS: Serial blood samples were obtained (admission, 24 hrs, and 48 hrs), and concentrations of CTpr, interleukin-6, and interleukin-8 were determined. Demographic and laboratory data from the patients were collected from the medical record. MEASUREMENTS AND MAIN RESULTS: Sixteen (29%) of the children met the criteria for bacterial sepsis. Plasma levels of CTpr and interleukin-8, but not interleukin-6, were increased at all time points in children with sepsis compared with those without sepsis. CTpr at 24 and 48 hrs after admission were reliable markers for sepsis (area under the curve = 0.92 and 0.908, respectively). Logistic regression using CTpr at 24 hrs in addition to interleukin-8 at 48 hrs produced the best-fit models associated with sepsis. Using cutoff values of CTpr >500 pg/mL and interleukin-8 >20 pg/mL produced a screening test for sepsis with 94% sensitivity and 90% specificity. CONCLUSIONS: Our data show the utility of a rapid and sensitive assay for CTpr combined with interleukin-8 as a highly sensitive and specific diagnostic marker of bacterial sepsis in febrile, neutropenic children. The use of these markers as a clinical tool may allow for better prognostication for clinicians and may eventually lead to more targeted therapies for this heterogeneous population.
Immune function across development, tissue repair, aging, and disease depends not only on signaling pathways but also on epigenetic architectures that determine whether coordinated transcriptional programs can be accessed and resolved. Increasing evidence indicates that epigenetic gene networks regulate the accessibility and reversibility of semi-stable immune states, shaping plastic, homeostatic, reparative, and degenerative configurations. We propose the concept of epigenetic transition windows, defined as temporally and contextually restricted intervals during which epigenetic constraints are relaxed, permitting coordinated and reversible transitions between immune states. During development, these windows are broad and support immune tolerance and adaptive plasticity. In adulthood they become spatially and temporally restricted, preserving stability while enabling conditional adaptation. With aging, they progressively narrow, contributing to chronic inflammation, impaired repair, and increased vulnerability to neurodegeneration. Conversely, pathological persistence of regulatory permissiveness may underlie immune evasion and sustained plasticity in cancer. We outline operational genomic readouts for quantifying transition windows, including chromatin accessibility variance, enhancer switching dynamics, reversibility metrics, and cross-cell coordination indices, and derive experimentally testable predictions that distinguish this model from pathway-centric or damage-centric explanations. By reframing immune dysfunction as a failure of regulated state transition rather than excessive signaling alone, this framework integrates inflammaging, trained immunity, immune resolution failure, and tumor immune escape within a unified regulatory architecture and provides a systems-level perspective on immune adaptability across the lifespan.
The malignant potential of oral lichen planus was assessed on the basis of observations in 722 patients found among 27,599 individuals examined in various epidemiologic studies in Kerala, Ernakulam district, India. Seven hundred and two patients with oral lichen planus were re-examined annually over a 10-year period with a mean observation period of 5.1 years. Most of the lesions (93%) were observed among tobacco users. Carcinoma developed in 3 (0.4%) patients with oral lichen planus. Clinically, all 3 had atrophic components in their lesions, and all were tobacco users. The relative risk of a lichen planus developing oral cancer compared to a tobacco user was estimated as 3.3. However, this relative risk was not significant. Histologically, 74% of the 94 biopsies from oral lichen planus showed epithelial atrophy. Two of the 3 in whom cancer developed also showed epithelial atrophy. It is felt that epithelial atrophy probably renders the mucosa more vulnerable to the carcinogenic action of tobacco. Although this study could not confirm the precancerous nature of this disease with a high degree of certainty, the disease did not appear to be innocuous either.
BACKGROUND: Functional decline threatens independent living and is common among individuals diagnosed with cancer, especially those who are elderly. The purpose of this study was to explore whether dietary and exercise practices are associated with physical function status among older cancer survivors. METHODS: Mailed surveys were used to ascertain data on physical function, dietary fat, fruit and vegetable (F&V) consumption, and exercise among elderly diagnosed with early stage (I-II) breast (N = 286) or prostate cancer (N = 402) within the past 18 months. RESULTS: Sixty-one percent of respondents reported diets with <30% of energy from fat, 20.4% reported F&V intakes of 5+ daily servings, and 44.6% reported regular vigorous exercise. Significant, independent associations were found between physical functioning and reported dietary fat intake, F&V consumption, and exercise. A simultaneous multiple regression model controlled for age, race, gender, time since diagnosis and concurrent health behaviors yielded the following estimates: (1) 0.2 increase in the SF-36 physical function subscale (PFS) score with each reported 1% decrease in percent energy from fat (p < .0001); (2) 0.9 increase in the SF-36 PFS score for each reported serving of F&V/day (p = .0049); and (3) 15.4 increase in the SF-36 PFS score with a positive response for regular vigorous exercise (p < .0001). CONCLUSIONS: Results of this cross-sectional survey suggest that regular vigorous exercise and consumption of diets low in fat and rich in F&Vs are associated with higher levels of physical functioning among older cancer survivors. Interventions that promote healthful lifestyle change may deliver considerable benefit within this ever increasing and vulnerable population.
The problem of emotional "burn-out" among health care professionals who work with cancer patients is a significant clinical issue. An interdisciplinary group of these health care service providers participated in a workshop aimed at identifying the major stresses which contribute to emotional "burn-out." While some of these stresses are unavoidable aspects of cancer treatment programs, participants also identified a set of coping strategies which seem helpful in reducing caretaker vulnerability to severe emotional exhaustion in oncology treatment settings.
Evidence is accumulating to suggest that selenium (Se) is an essential trace element for man and is reviewed with emphasis on those aspects peculiar to New Zealand. The extremely low Se levels in New Zealand soils results in a low Se content of foods, low dietary intakes, low urinary excretions, and low blood Se concentrations and glutathione peroxidase activities. Of these, plasma Se gives a short-term index of nutritional status while erythrocyte Se and glutathione peroxidase activities give a long-term index. The consequences of the low Se status of New Zealanders are not immediately apparent as a deficiency disease has not been detected in residents consuming a normal diet. However a Se-responsive muscular syndrome has been described in a surgical patient on total parenteral nutrition. Similar groups that might be vulnerable to a Se deficiency are children with metabolic disorders consuming synthetic protein diets, premature babies and infants during the first few months of life, and patients with cancer whose lowered dietary intake is coupled with the traumatic nature of their disease. Other groups that have been studied in relation to a possible role for Se in specific illnesses are patients with cardiovascular disease and hypertension, rheumatoid arthritis and other muscular syndromes and surgical patients with or without cancer. It is not yet possible to predict a minimum Se requirement for health but it appears that the intake of New Zealanders might be on the borderline. At present supplementation by the general population is not justified, but may be necessary for certain vulnerable groups such as patients on restricted diets. The most effective means of supplementation for increasing the Se status of New Zealanders is under study.
Knowledge about acute confusion (AC) has grown rapidly during the past decade, but very few studies have focused specifically on AC episodes associated with the end of life. Although experienced oncology clinicians accept that AC is common near the end of life, little is known about the frequency, nature, course, and timing of AC during this critical stage of life in patients with terminal cancer. Data suggest patients with advanced cancer have reversible causes of delirium, where appropriate treatment can result in improved outcomes. The data for this article are drawn from a larger study investigating the incidence, prevalence, behaviors, and outcomes of AC in acutely ill medical patients. The diagnosis of AC was ascertained using the NEECHAM Confusion Scale. Of the 117 participants included in the larger study, 16 developed delirium (cumulative incidence estimate, 14%) and 10 died within 1 year of the index hospitalization. These 10 cases were categorized in two groups: those with a cancer-related diagnosis (n = 6) and those without cancer (n = 4). To further describe the nature of AC near the end of life, two case studies are presented. Because all previous studies were conducted using samples consisting of patients with cancer, it is unknown whether the findings reported in previous studies hold for other terminal illnesses, such as chronic obstructive pulmonary disease or heart failure. The data presented in this article suggest there are differences in baseline vulnerability (e.g., cognitive status) and the timing of AC in relation to death. These differences need to be explored in a larger sample of individuals both with and without a diagnosis of cancer. The severity and course of AC in the terminally ill population needs to be described to gain a better understanding of end-of-life AC phenomenology (e.g., signs, patterns, subtypes). Armed with this information, health care providers will then be able to develop and test AC-specific treatments of patients, as well as counsel and support family members of patients experiencing AC.
BACKGROUND: Most authorities advocate mammogram screening for breast cancer beginning at age 40 based on the age-specific distribution and incidence of breast cancer in the general population. This policy has been bolstered by studies that demonstrate that, for the general population, mammography in the 40-49 age bracket reduces mortality. However, it also has been reported that African-American breast cancer patients are diagnosed more often than white patients below the age of 40. Young African-American women are also more likely to have advanced disease at the time of diagnosis with predictably higher mortality. The purpose of this investigation is to explore the question, whether a subset of African-American women, age 30-39, by virtue of increased vulnerability, would benefit from early mammogram screening. STUDY DESIGN: The age-specific distribution (age 30-84) of African-American and white breast cancer patients in five State cancer registries were compared. Prognostic indicators (tumor size and nodal status) in two of the five registries in African-American and white breast cancer cases below the age of 40 were compared. Age-specific incidence in the 30-39 age group and the relative populations of black and white women in the United States were noted in the Surveillance Epidemiology and End Report (SEER) (1994-1998) and The U.S. Census 2000. RESULTS: The differences of age-specific distribution and age-specific incidence of African-American and white breast cancer patients were found to be significant. More than 10% of African-American women with breast cancer were diagnosed before age 40 compared to 5% of white patients. The incidence of breast cancer (SEER Report 1994-1998) in the 30-39-age bracket for African-American and white women was 48.9 and 40.2 at the 95% confidence level, while the proportion of African-American and white women reported by the Census Bureau was not too dissimilar, 15.8% and 14.6% respectively. Prognostic indicators (tumor size and nodal status) support the notion that young African-American women are more likely to have advanced disease at diagnosis. CONCLUSIONS: African-American women in the 30-39 age group have twice the age-specific distribution, have a higher incidence compared to their white counterparts, and exhibit more ominous prognostic signs. This study provides evidence that African-American women in the 30-39 age category represent a high-risk group that may benefit from efforts at earlier detection. Although mammography remains the preferred screening modality, investigators have pointed out difficulties encountered when using mammography in young women, including low sensitivity, high breast density, cost/benefit concerns, and low positive predictive value. Nevertheless, the increasing mortality and persistent racial incidence gap in young African-American women, age 30-39, argue for considering early screening mammography in spite of recognized concerns.
BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n = 65) or routine nursing only (n = 65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6 months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6 months ranged from small for resilience (D = 0.28) and avoidance coping (D = 0.26) to moderate for confrontation coping (D = 0.60) and resignation coping reduction (D = -0.51), and large for attributional style (D = 0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.
Planning national and regional cancer control strategies is difficult. At present, cancer experts and planners rely on global subjective judgment to estimate the effectiveness and cost of different programs, and to set priorities. The complexity of the problem makes this approach vulnerable to oversimplification and error. Computer models can be very powerful aids to planning, enabling decision makers to break a problem into parts for which data exist, and reconstructing the parts to estimate the effect of a virtually limitless variety of cancer control activities, on a large number of important clinical and economic outcomes. CAN*TROL has been developed to serve this need. CAN*TROL has been used in the U.S., Chile and India, and is scheduled for use in several other countries.
Herpes simplex viruses that lack ICP34.5 are neuroattenuated and are presently being considered for cancer and gene therapy in the nervous system. Previously, we documented the focal presence of the latency-associated transcripts (LATs) in the hippocampi of immunocompromised mice after intracranial (IC) inoculation of an ICP34.5-deficient virus called strain 1716. To characterize further the biological properties of strain 1716 in the CNS of immunocompetent mice, we determined the extent of viral gene expression in different cell types and regions of the CNS after stereotactic IC inoculation of this virus. At survival times of > 30 d after inoculation, we found that (1) infectious virus was not detectable by titration and immunohistochemical studies; (2) neurons harbored virus as demonstrated by the detection of the LATs by in situ hybridization (ISH); (3) transcripts expressed during the lytic cycle of infection were not detected by ISH; and (4) subsets of neurons were selectively vulnerable to latent infection, depending on the site of inoculation. These results suggest that the absence of ICP34.5 does not abrogate latent infection of the CNS by strain 1716. Additional studies of strain 1716 in the model system described here will facilitate the elucidation of the mechanisms that regulate the selective vulnerability of CNS cells to latent viral infection and lead to the development of ICP34.5 mutant viruses as therapeutic vectors for CNS diseases.
Breast cancer is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age. Rising incidence, increased risk among migrants to higher risk regions, and poor prediction of individual risk have prompted a search for additional modifiable factors. Risk factors for breast cancer include reproductive characteristics associated with estrogen and other hormones, pharmaceutical hormones, and activities such as alcohol use and lack of exercise that affect hormone levels. As a result, investigation of hormonally active compounds in commercial products and pollution is a priority. Compounds that cause mammary tumors in animals are additional priorities. Animal models provide insight into possible mechanisms for effects of environmental pollutants on breast cancer and identify chemical exposures to target in epidemiologic studies. Although few epidemiologic studies have been conducted for chemical exposures, occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic aromatic hydrocarbons (PAHs). Population-based studies have been limited to a few organochlorine compounds and PAHs and have been mostly negative. A variety of challenges in studies of breast cancer and the environment may have contributed to negative findings. Lack of exposure assessment tools and few hypothesis-generating toxicologic studies limit the scope of epidemiologic studies. Issues of timing with respect to latency and periods of breast vulnerability, and individual differences in susceptibility pose other challenges. Substantial work is needed in exposure assessment, toxicology, and susceptibility before we can expect a pay-off from large epidemiologic studies of breast cancer and environment.
OBJECTIVE: To compare nurse practitioner (NP) and physician rates of breast and cervical cancer screening among poor, elderly black women. DESIGN: A quasi-experimental design was used to compare pre- and postintervention annual screening rates. Rates were determined by medical record audits. SETTING: Two urban public hospital primary care clinics served as the study sites. PATIENTS: All women aged 65 years or more were eligible to participate. INTERVENTIONS: Women were offered screening by a NP during a routine visit in the intervention site; a physician reminder system was used in the control site. MAIN RESULTS: Baseline annual screening rates were comparable in the two study sites. At the end of the study period, rates were significantly higher in the NP site, compared with the control. In the NP clinic, the annual rate of Pap tests increased to 56.9% from the baseline of 17.8%, and mammographies increased to 40% from 18.3%. In comparison, rates remained low in the control site, increasing only to 18.2% of women receiving Pap tests from a baseline of 11.8%, and remaining at 18% for mammography. CONCLUSIONS: Use of a NP to deliver same-day screening is an effective strategy to target poor, elderly black women for breast and cervical cancer screening. However, even with the substantial increases in rates obtained with the NP intervention, screening in this vulnerable population remains below nationally targeted levels.