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Background We evaluated oncological changes in patients with squamous cell carcinoma of the anus (SCCA) treated by chemoradiotherapy (CRT) from a large UK institute, to derive estimates of contemporary outcomes. Methods We performed a treatment-cohort analysis in 560 patients with non-metastatic SCCA treated with CRT over 25 years. The primary outcomes were 3-year loco-regional failure (LRF), 5-year overall survival (OS), and 5-year cancer-specific survival (CSS). We developed prediction models; and overlaid estimates on published results from historic trials. Results Age distributions, proportions by gender and cT stage remained stable over time. The median follow-up was 61 (IQR: 36–79) months. Comparing the first period (1990–1994) with the last period (2010–2014), 3-year LRF declined from 33 to 16% (Ptrends Ptrends = 0.001); and 5-year CCS increased from 62% in to 80% (Ptrends = 0.001). For 2020, the models predicted a 3-year LRF of 14.7% (95% CIs: 0–31.3); 5-year OS of 74.7% (95% CIs: 54.6–94.9); and 5-year CSS of 85.7% (95% CIs: 75.3–96.0). Reported oncological outcomes from historic trials generally underestimated contemporary outcomes. Conclusions Current and predicted rates for 3-year LRF and 5-year survivals are considerably improved compared with those in historic trials.

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are an established treatment for pseudomyxoma peritonei (PMP), but it is a major surgical procedure and may be associated with long-term morbidity. To date, health-related quality-of-life (HRQL) data among survivors are lacking. Methods A two-period qualitative study investigated patients undergoing CRS-HIPEC for PMP at a national peritoneal tumor center between 2003 and 2011. First, the European Organization for Research and Treatment (EORTC)-QLQ C30 HRQL questionnaire was used longitudinally preoperatively and at postoperative months 3, 6, 9, 12, 18, and 24, then yearly thereafter. Second, it was updated in 2016 as a cross-sectional study. Both studies were compared with age- and sex-matched reference populations (one-way t tests). Results A total of 553 longitudinal HRQL questionnaires were completed for 137 patients, truncated at 60 months. In the 2016 update, 85 responses were received from 103 survivors (mean follow-up period, 8.11 years). Patients' physical, role, and social function scores were impaired until 12 months postoperatively, after which the scores did not differ significantly from those of with reference populations. Similarly, fatigue, appetite loss, insomnia, and financial difficulties worsened significantly compared with reference populations in the first 12-months and then normalized. In contrast, impaired cognitive function (82.3 vs 88.5; P = 0.017), constipation (13.7 vs 7.3; P = 0.032), and diarrheal symptoms (15.1 vs 4.9; P = 0.0006) persisted through both periods. Global health scores did not differ significantly from those of the reference population. Conclusions Beyond 12 months postoperatively, CRS-HIPEC for PMP is associated with a good quality of life except for some cognitive functional impairment and bowel disturbances.

Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion of pseudomyxoma peritonei, which, if treated suboptimally, may later disseminate throughout the abdominal cavity. We previously demonstrated the role of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) to reduce the dissemination risk. Here we describe the feasibility and safety of minimal access cytoreductive surgery (MACRS) and HIPEC as an alternative to the open approach. We evaluated patients with LAMNs at risk of dissemination (known as LAMN II) who were referred to a national treatment centre between 2010 and 2012 and comparison is made between this group and patients undergoing open CRS and HIPEC for the same pathology over the same time period. Of the 39 patients with LAMN II, 10 patients were treated by MACRS and HIPEC and 7 were treated by an open approach. Among the MACRS procedures, there were no conversions to open surgery; median procedure length, median length of stay, and complication rates were similar between groups and there were no 30-day deaths. After 3- and 11-months median follow-up respectively, no patients have evidence of disease progression. The present series demonstrates that MACRS and HIPEC is a feasible and safe alternative to the open procedure with the advantage of smaller abdominal wounds and comparable morbidity and inpatient stay. Longer follow-up is needed to assess the impact on disease progression.

The objectives of the study were: first, to determine the prevalence of traditional medicine (TM) and complementary and alternative medicine (CAM) use in head and neck cancer patients in Ireland; second, to educate ourselves on the plethora of CAM/TM options available to patients outside the dominion of conventional medicine. The study design consisted of a cross-sectional survey carried out in three head and neck cancer centres. Self-administered questionnaires were distributed to 110 head and neck cancer patients attending the three cancer centres and data were collected for statistical analysis. A total of 106 patients completed the questionnaire; 21.7% of the participants used CAM/TM since their diagnosis with head and neck cancer. CAM/TM usage was higher in female (34.3%) than in male patients (16.2%). CAM/TM use was more common in the 41-50-year age group, in patients with higher educational levels and those holding strong religious beliefs, and also in married than single patients. The most common types of CAM/TM used were spiritual and laying on of hands. The most common reasons reported for using CAM/TM were to counteract the ill effects of treatment and increase the body's ability to fight cancer. Sources of information on CAM/TM were friends (65%), family (48%) and media (21%). This survey reveals a high prevalence of CAM/TM use in head and neck cancer patients, hence emphasising the need for otolaryngologists to educate themselves on the various therapies available to be able to provide informative advice. There is an urgent need for evidence-based investigation of various CAM/TM therapies currently offered to patients.

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.

Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin, characterised by excess intra-abdominal mucin production leading to high morbidity and mortality. While histological features are frequently indolent, this tumour disseminates aggressively throughout the abdominal cavity, yet seldom metastasises. This study determined the expression of several markers of colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20 and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9 (IL-9), IL-9 receptor (IL-9Ralpha)), and cell adhesion (N- and E-cadherin, vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa (n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20-/CK7- pattern was rare in PMP (Fisher's exact test: P=0.001). Similarly, expressions of mucin-related proteins were comparable for adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible epithelial-mesenchymal transition state. Primary PMP cell cultures were successfully maintained and demonstrated marker expressions similar to those seen in in vivo tissues. These early characterisation studies demonstrate similarities between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin phenotype that may characterise the distinct non-metastasising behaviour of PMP, and form the basis for future mechanistic and therapy-targeting research.

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.

Since its very first use in 1985, robotic surgery has evolved and revolutionized minimal access surgery over past three decades [1]. The benefits of 3D vision, unmatched dexterity of the Endo Wrist instruments, precise dissection and better ergonomics are well recognized advantages of robotic surgery [2]. These clear advantages over conventional open surgery and laparoscopy can be utilized to perform difficult pelvic dissections. The authors report the use of robotic surgery in posterior pelvic clearance in a young female who had locally advanced rectal cancer. It also highlights the multi-disciplinary approach in the management of a patient with locally advanced rectal cancer.

The patterns of risk association between circulating levels of insulin-like growth factor (IGF)-I, and its main binding protein, IGFBP-3, differ between smoking and nonsmoking-related cancers. To investigate this observation further, we measured serum IGF-I, IGF-II and IGF-binding protein-3 concentrations in 232 men and 210 women (aged 55-64 years), and related peptide levels to smoking characteristics. Current smoking was associated with significant reductions in mean IGFBP-3 levels in men assessed by the number of cigarettes smoked daily (P(trend)=0.007) and pack-years smoked (P(trend)=0.03). Mean IGF-I levels decreased with increasing cigarette use in men (P(trend)=0.11). There were no patterns of association between smoking and IGF peptides in women. For male former vs never smokers, there were no differences in mean IGF-I and IGFBP-3 concentrations, suggesting that smoking cessation is associated with normalisation of peptide concentrations.

Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are members of the VEGF family of cytokines and have angiogenic and lymphangiogenic actions. In gastric adenocarcinoma, VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis and in some reports, venous invasion and reduced 5-year survival. Patients with gastric adenocarcinomas containing high levels of VEGF-C expression have significantly reduced 5-year survival rates, and VEGF-C expression is an independent prognostic risk factor for death. The role of VEGF-C in oesophageal squamous and colorectal cancer and VEGF-D in colorectal cancer is not clear, with conflicting reports in the published literature. In order to exploit potential therapeutic applications, further research is necessary to define the precise roles of these cytokines in health and disease.

CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40–9.00) and 3.10 (range 0.90–8.00), respectively. Kaplan–Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor–ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.