Pseudomyxoma peritonei (PMP) is a rare neoplastic process characterised by progressive intra-abdominal dissemination of mucinous tumour, and generally considered resistant to systemic chemotherapy. A ...phase II study in patients with advanced unresectable PMP was undertaken to evaluate the combination of systemic concurrent mitomycin C (7 mg m(-2) i.v. on day 1) and capecitabine (1250 mg m(-2) b.d. on days 1-14) in a 3-weekly cycle (MCap). Response was determined by semiquantitative assessment of disease volume on serial computed tomographic (CT) scans and serum tumour marker (CEA, CA125, CA19-9) changes at 12 weeks. Between 2003 and 2006, 40 patients were recruited through a national centre for the treatment of peritoneal surface tumours. At baseline, 23 patients had progressive disease and 17 had stable disease. Of 39 assessable patients, 15 (38%, 95% confidence intervals (CIs): 25, 54%) benefited from chemotherapy in the form of either reductions in mucinous deposition or stabilisation of progressive pretreatment disease determined on CT scan. Notably, two patients, originally considered unresectable, following MCap and re-staging underwent potentially curative cytoreductive surgery. Grade 3/4 toxicity rates were low (6%, 95% CIs: 4, 9%). Twenty out of 29 assessed patients (69%, 95% CIs: 51, 83%) felt that their Global Health Status improved during chemotherapy. This is the first trial to demonstrate an apparent benefit of systemic chemotherapy in patients with advanced unresectable PMP.
PURPOSE:Treatment of peritoneal surface malignancies with combined cytoreductive surgery and heated intraperitoneal chemotherapy may improve oncologic outcome. To better define treatment pathways, ...five-year results in patients referred to one of two centralized national treatment centers in the United Kingdom were analyzed.
METHODS:A prospective database of patients referred to the Manchester Peritoneal Tumor Service, established in 2002, was analyzed. Outcomes were evaluated using Kaplan-Meier life tables and Cox models.
RESULTS:Two hundred seventy-eight patients (median age, 56.9 (range, 16–86) years) were considered by a dedicated multidisciplinary team and tracked on seven clinical pathways. Among the 118 surgically treated, the most common diagnosis was pseudomyxoma peritonei (101 patients, 86%). Major complications occurred in 11 patients (9%); there was no 30-day mortality. Where complete cytoreduction was achieved, three-year and five-year tumor-related survival rates were 94% and 86%, respectively. In the Cox model, incompleteness of cytoreduction (P = 0.001) and high-grade tumor (P < 0.0001) were independent prognosticators of poor outcome.
CONCLUSION:The establishment of a national treatment center has allowed refinement of techniques to achieve internationally recognized results. Having achieved low levels of morbidity and mortality in the treatment of mainly pseudomyxoma peritonei of appendiceal origin, the technique of cytoreductive surgery and heated intraperitoneal chemotherapy may be considered for peritoneal carcinomatosis of colorectal origin.
Objective: Two small studies have suggested that family carers of people with dementia may be a high-risk group for suicide. The objective of this study was to further explore the rate of suicidal ...ideation in a large sample of carers and identify psychosocial risk and protective factors.
Method: A cross-sectional survey was conducted with 566 family carers. The survey included measures of suicidality, self-efficacy, physical health, depression, anxiety, hopelessness, optimism, burden, coping strategies, and social support.
Results: Sixteen percent of carers had contemplated suicide more than once in the previous year. There were univariate differences between suicidal and non-suicidal carers on self-efficacy, social support, coping, burden, depression, anxiety, hopelessness, optimism, reasons for living, and symptoms of dementia, as well as age and income management. In a multivariate model, age, depression, and reasons for living predicted suicidal ideation. In tests for mediation, satisfaction with social support and dysfunctional coping had indirect effects on suicidal ideation via depression.
Conclusion: Family carers of people with dementia have high rates of suicidal ideation, with depression a risk factor and increasing age and reasons for living as protective factors. Depression and reasons for living should be targeted in interventions to reduce suicide risk in dementia carers.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
34.
Management of Local Disease Relapse Renehan, A. G.; O'Dwyer, S. T.
Colorectal disease,
February 2011, Letnik:
13, Številka:
s1
Journal Article
Objective Microvessel density (MVD) has been studied as a prognostic marker in human cancers. Quantification of lymphatic vessel density (LVD) is now possible by using new antibodies. Expression of ...the lymphangiogenic growth factors, VEGF‐C and VEGF‐D, is associated with poorer clinicopathological outcomes in various tumours. The aim of this study was to quantify LVD and MVD in colorectal cancer, determine the relationship between LVD, MVD and clinicopathological variables and examine the relationship between LVD and tumour expression of VEGF‐C and VEGF‐D.
Method Thirty primary colorectal cancers were immunostained for CD34, lymph vessel endothelial hyaluronan receptor‐1 (LYVE‐1), VEGF‐A and VEGF‐D using standard techniques. LVD and MVD were determined by Chalkley grid counting. Tumours were assessed for the presence or absence of LYVE‐1 positive lymphatics at different areas within the tumour and the tumour was scored for VEGF‐C and VEGF‐D immunostaining intensity at the invading tumour edge. Non‐parametric tests were used for statistical analysis and a P‐value of <0.05 was taken as significant.
Results Lymph vessel endothelial hyaluronan receptor‐1 was an excellent lymphatic vessel marker. Within normal bowel wall, lymphatic vessels were found rarely in the superficial colonic mucosa, but were numerous in the submucosa and muscularis propria. In the majority of tumours, lymphatic vessels were located in the peri‐tumoural area, intra‐tumoural vessels were sparse and tended to be narrow with closed lumina. At the invading tumour edge, VEGF‐C expression was higher (P = 0.028) and VEGF‐D expression lower (P = 0.011), in tumours in which lymphatic vessels were present. No significant differences between LVD and any clinicopathological variable or route of metastasis were identified.
Conclusion Lymphatic vessel density and MVD can be quantified in colorectal carcinoma using immunohistochemical techniques. The balance between expression of VEGF‐C and VEGF‐D at the invading tumour edge may enhance lymphatic metastasis, by promoting tumour lymphangiogenesis or by activation of pre‐existing lymphatic vessels. No relationship was identified between LVD and clinicopathological variables.
A meta-analysis of six randomised trials demonstrated that intensive followup in colorectal cancer was associated with an absolute reduction in all-cause 5-year mortality of 10% (95% confidence ...interval (CI): 4-16)--however, only two percent (95% CI: 0-5) was attributable to cure from salvage re-operations. We postulate that other factors, such as increased psychological well-being and/or altered lifestyle, and/or improved treatment of coincidental disease may contribute to the remaining lives saved, and form important future research questions.
There are conflicting associations between growth factor expression and clinicopathological variables in colorectal cancer. This study aimed to define the expression of members of the VEGF family and ...the receptor, VEGFR2, in primary and metastatic sites of colorectal cancer and their relationship to metastatic potential. Thirty colorectal cancers, 12 lymph node metastases and 9 liver metastases were immunostained for VEGF-A, VEGF-C, VEGF-D and VEGFR2. VEGFR2 was expressed by endothelial cells and by the malignant epithelium. VEGF-C and VEGFR2 were co-expressed in the same territory and correlated throughout the primary tumour and in metastatic lymph nodes, but not in liver metastases. Their expression at the invasive tumour edge correlated with expression in metastatic nodes. The benefit of anti-VEGF antibodies might be increased by directing additional therapies against VEGF-C or against the kinase receptors to target redundancy in the system. A component of the therapeutic benefit might be due to a direct anti-tumour effect as well as an anti-angiogenic effect.
Anal cancer requires a multidisciplinary approach to treatment with often complex interventions. Little is known regarding the associated costs and resource use.
Patient records were extracted from a ...national hospital database to estimate the number of patients treated for anal cancer in England. Identified resource use was linked to published UK cost estimates to quantify the reimbursement of treatment through the Payment by Results system. A mathematical model was developed simultaneously to validate findings and to calculate the average 10-year cost of treating a squamous cell anal carcinoma case from diagnosis. The model utilised data from the Association of Coloproctology of Great Britain and Ireland's anal cancer position statement.
On average, 1,564 patients were admitted to hospital and 389 attended an outpatient facility per year. The average annual cost per inpatient and outpatient ranged from £4,562-£5,230 and £1,146-£1,335, respectively. Based on the model estimates, the inflated cost per case was between £16,470-£16,652. Results were most sensitive to the mode of admission for primary treatment and the costs of staging/diagnosis (inflated range: £14,309-£23,264).
Despite limitations in the available data, these results indicate that the cost of treating anal cancer is significant. Further observational work is required in order to verify these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer (CRC) is well-established, requiring molecular analysis of primary or metastatic biopsies. We aim to review ...concordance between primary CRC and its metastatic sites.
A systematic review and meta-analysis of all published studies (1991–2018) reporting on biomarker concordance between primary CRC and its metastatic site(s) was undertaken according to PRISMA guidelines using several medical databases. Studies without matched samples or using peripheral blood for biomarker analysis were excluded.
61 studies including 3565 patient samples were included. Median biomarker concordance for KRAS (n = 50) was 93.7% 67–100, NRAS (n = 11) was 100% 90–100, BRAF (n = 22) was 99.4% 80–100, and PIK3CA (n = 17) was 93% 42–100. Meta-analytic pooled discordance was 8% for KRAS (95% CI = 5–10%), 8% for BRAF (95% CI = 5–10%), 7% for PIK3CA (95% CI = 2–13%), and 28% overall (95% CI = 14–44%). The liver was the most commonly biopsied metastatic site (n = 2276), followed by lung (n = 438), lymph nodes (n = 1123), and peritoneum (n = 132). Median absolute concordance in multiple biomarkers was 81% (5–95%).
Metastatic CRC demonstrates high concordance across multiple biomarkers, suggesting that molecular testing of either the primary or liver and lung metastasis is adequate. More research on colorectal peritoneal metastases is required.
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