Quality of life in patients treated for anal carcinoma-a systematic literature review.

PURPOSE: Anal cancer is a mainly treated with chemoradiotherapy. A small number of patients undergo salvage surgery. There are few published studies investigating quality of life and functional outcome after treatment for anal cancer. The aim of this review was to explore the literature and identify areas for further research. METHODS: A search was conducted in Medline using MESH terms related to anal cancer and quality of life. Two investigators selected and reviewed articles based on titles and abstracts. Three investigators read and reviewed the included articles and collected relevant data. The included articles were evaluated using the minimum standard checklist, and key findings were summarised in a chart. RESULTS: Some 15 articles, and a total of 802 patients, were deemed eligible. The results differed slightly among the studies. The incidence of symptoms such as fatigue, nausea, insomnia and appetite loss was higher than among healthy volunteers. Bowel function, urinary function and sexual function were negatively affected. Some studies found that, compared with the normal population, anal cancer survivors scored clinically significant worse in the functional scales in QLQ-C30. CONCLUSION: In conclusion, it is apparent that several functional problems affect the quality of life of patients with anal cancer. There are few studies which have investigated quality of life after treatment for anal cancer. Interventions to address issues related to anal cancer treatment may improve long-term quality of life in this patient group. TRIAL REGISTRATION: CRD42017059787.

Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer.

PURPOSE: The aim of study was to investigate the relationship between folate concentration and expression of folate-associated genes in tumour, mucosa and plasma of patients with colorectal cancer, after intraoperative administration of bolus leucovorin (LV). METHODS: Eighty patients were randomized into four groups to receive 0, 60, 200, or 500 mg/m2 LV, respectively. Tissue and plasma folate concentrations were assessed by LC-MS/MS. Gene expression of ABCC3/MRP3, FPGS, GGH, MTHFD1L, SLC46A1/PCFT, and SLC19A1/RFC-1 was determined using quantitative PCR. RESULTS: The folate concentration in tumour increased with increasing dosage of LV. Half of the patients treated with 60 mg/m2 did not reach a level above the levels of untreated patients. A significant correlation between folate concentration in tumour and mucosa was found in untreated patients, and in the group treated with 60 mg/m2 LV. The 5-MTHF/LV ratio correlated negatively with folate concentration in mucosa, whereas a positive correlation was found in tumour of patients who received 200 or 500 mg/m2 LV. A positive correlation was found between folate concentration and expression of all genes, except MTHFD1L, in patients who received LV. There was a negative correlation between 5-MTHF concentration in plasma of untreated patients and expression of GGH and SLC46A1/PCFT in tumour. CONCLUSIONS: The results indicate the possibility of using the individual plasma 5-MTHF/LV ratio after LV injection as a surrogate marker for tissue folate concentration. Expression of several folate-associated genes is associated with folate concentration in tissue and plasma and may become useful when predicting response to LV treatment.

Correction to: The Surgical Teams' Perception of the Effects of a Routine Intraoperative Pause.

In the original article there is an error in the legend in Fig. 4. Following is corrected Fig. 4.

The Surgical Teams' Perception of the Effects of a Routine Intraoperative Pause.

BACKGROUND: A pause routine may reduce stress and errors during surgery. The aim of this study was to explore how the team, divided into the different professional groups, perceived the implementation of a pause routine and its possible impact on safety. METHODS: A pause routine was introduced at a University hospital operating theatre in Sweden in 2013. Questionnaires were distributed about 1 year later to all members of the operating theatre team. The questions included different perspectives of possible effects of the pause routine. RESULTS: A majority were positive to scheduled pauses. The surgeons often felt refreshed and at times changed their view on both anatomy and their surgical strategy. They were also perceived by other team members as improved regarding communication. All groups felt that patient safety was promoted. There were differences by profession in perception of team communication. CONCLUSIONS: The pause routine was well perceived by the surgical team. A majority believed that scheduled and regular pauses contribute to improved patient safety and better team communication. There were also findings of differences in communication and experience of team coherence between personnel categories that could benefit from further acknowledgement and exploration.

Case Mix Difference Can Affect Evaluation of Outcome of Treatment for Colorectal Cancer.

AIM: To explore the potential effects of patient selection, for example by organization, on survival as outcome parameter in colorectal cancer treatment. PATIENTS AND METHODS: The main cohort was identified in a Hospital-based registry and outcome data of all 2,717 patients operated on for colorectal cancer between 2000-2011 were evaluated. A simulation of different center settings was performed using several potential selection criteria, including emergency cases, referral surgery and palliative resection, and used for comparison of outcome data. RESULTS: Overall survival and cancer-specific survival can be significantly affected in both short-term (30-/90-day) mortality and long-term survival by factors of organizational level. CONCLUSION: Survival data as an outcome parameter can be affected by the composition of the patient cohort and thus reflect possible selection bias for example due to organization, referral patterns and practice customs. This potential bias should be acknowledged when making inter-hospital comparisons of outcome.

Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer.

BACKGROUND: Modufolin® ([6R]-5,10-methylene tetrahydrofolate; [6R]-MTHF) is an endogenous biomodulator that is being developed as an alternative to leucovorin, a folate prodrug used in the treatment of colorectal cancer. The objective of this phase 1 dose de-escalation trial was to estimate the minimum tolerated dose of [6R]-MTHF to be used in combination with pemetrexed 500 mg/m(2) in the neoadjuvant treatment of patients with rectal cancer. METHODS: Adult patients (≥18 years) with resectable rectal adenocarcinoma were allocated to [6R]-MTHF doses of 500, 100, 50, and 10 mg/m(2) in combination with pemetrexed 500 mg/m(2). [6R]-MTHF was administered as an intravenous (i.v.) bolus injection 1 week prior to the first dose of pemetrexed and then once weekly for 9 weeks; pemetrexed was administered by i.v. infusion once every 21 days for three cycles. RESULTS: Twenty-four patients (mean [SD] age, 63.1 [12.9] years) were enrolled in the study. A total of 72 treatment-related adverse events (AEs) were reported, of which the most common were fatigue (n = 17; 23.6 %), nausea (n = 10; 13.9 %), and diarrhea (n = 5; 6.9 %). The incidence of treatment-related AEs by [6R]-MTHF dose level (500, 100, 50, 10 mg/m(2)) was 11.1 % (n = 8), 13.9 % (n = 10), 45.8 % (n = 33), and 29.2 % (n = 21), respectively. There were no dose-limiting toxicities, and only two (2.8 %) treatment-related AEs were grade 3 in severity. Of the 11 serious AEs reported, none were considered to be related to [6R]-MTHF treatment. CONCLUSIONS: The results of this phase 1 study indicate that the estimated minimum tolerated dose of [6R]-MTHF was 100 mg/m(2) once weekly in combination with pemetrexed 500 mg/m(2). The low toxicity profile of [6R]-MTHF supports its further evaluation as a component of systemic chemotherapy in the management of colon and rectal cancer.

A pharmacokinetic and pharmacodynamic investigation of Modufolin® compared to Isovorin® after single dose intravenous administration to patients with colon cancer: a randomized study.

PURPOSE: Leucovorin is commonly used as folate supplement in 5-fluorouracil-based chemotherapy, but needs to be converted to active 5,10-methylenetetrahydrofolate (methyleneTHF) intracellularly. This provides for interindividual differences. MethyleneTHF has recently been developed into the stable, distributable drug, Modufolin®. The aim was to compare the concentration of folate metabolites in tumor, mucosa, and plasma of patients with colon cancer after administration of Modufolin® or Isovorin® (levo-leucovorin). METHODS: Thirty-two patients scheduled for colon resection were randomized to receive Modufolin® or Isovorin® at dosage of 60 or 200 mg/m². The study drug was given as one i.v. bolus injection after anesthesia. Plasma was collected for pharmacokinetic (PK) analysis before, during, and after surgery. Tissue biopsies were collected at surgery. Folate metabolites were analyzed by LC-MS/MS. RESULTS: MethyleneTHF and THF concentrations were significantly higher in mucosa (p < 0.01, both dosages) and tumors (p < 0.01, 200 mg/m²) after Modufolin® as compared to Isovorin® administration. The results correlated with PK observations. The Modufolin® to Isovorin® C(max) ratio for methyleneTHF was 113 at 200 mg/m² and 52 at 60 mg/m²; the AUC(last) ratios were 17 and 9, respectively. The THF plasma concentrations were also higher after Modufolin® administration (C(max) ratio 23, AUC(last) ratio 13 at 200 mg/m²; C(max) ratio 15, AUC(last) ratio 11 at 60 mg/m²). CONCLUSION: Modufolin® administration resulted in significantly higher methyleneTHF levels than Isovorin® and may potentially increase the efficacy of 5-fluorouracil-based chemotherapy. The results encourage further evaluation of Modufolin® as a substitute to Isovorin® including the potential clinical benefits.

A population-based cohort study on adherence to practice guidelines for adjuvant chemotherapy in colorectal cancer.

BACKGROUND: The value of adjuvant chemotherapy in colorectal cancer is well studied, and guidelines have been established. Little is known about how treatment guidelines are implemented in the everyday clinical setting. METHODS: This national population-based study on nearly 34,000 patients with colorectal cancer evaluates the adherence to present clinical guidelines for adjuvant chemotherapy. Virtually all patients with colorectal cancer in Sweden during the years 2007-2012 and data from the Swedish Colorectal Cancer Registry were included. RESULTS: In colon cancer stage III, adherence to national guidelines was associated with lower age, presence of multidisciplinary team (MDT) conference, low co-morbidity, and worse N stage. The MDT forum also affected whether or not high-risk stage II colon cancer patients were considered for adjuvant chemotherapy. Rectal cancer patients both in stage II and III were considered for adjuvant chemotherapy less often than colon cancer patients, but the same factors influenced the decision. Adjuvant chemotherapy was started later than eight weeks after surgery in 30% of colon cancer patients and in 38% of rectal cancer patients. CONCLUSIONS: In Sweden, the adherence to national guidelines for adjuvant chemotherapy in colon cancer stage III is acceptable in younger and healthier patients. MDT conferences are of major importance and affect whether patients are recommended for adjuvant chemotherapy. Special consideration needs to be given to certain subgroups of patients, particularly older patients and patients with poorly differentiated tumors. There is a need to shorten the waiting time until start of chemotherapy.

Folate levels measured by LC-MS/MS in patients with colorectal cancer treated with different leucovorin dosages.

PURPOSE: Calcium folinate (leucovorin), which is converted in vivo into biologically active folate, enhances the potency of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer. A common dosage of leucovorin in adjuvant and palliative settings is 60 mg/m(2). The aim was to determine the levels of tetrahydrofolate (THF), 5,10-methylenetetrahydrofolate (methyleneTHF), and 5-methyltetrahydrofolate (methylTHF) in tumour and mucosa of colorectal cancer patients who received different dosages of leucovorin intravenously at time of surgery. METHODS: Eighty patients scheduled for colorectal resection with indication of colorectal cancer were randomised into four groups to receive leucovorin at 0, 60, 200, or 500 mg/m(2), respectively. Blood samples were taken 10 and 30 min after leucovorin administration. Biopsy samples from tumour and mucosa were collected and snap-frozen at surgery. The levels of THF, methyleneTHF, and methylTHF in tumour and mucosa were assessed by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-MS/MS) and the results were related to clinical diagnosis and therapeutic regimens. RESULTS: The folate levels in tissue revealed extensive inter-individual variability. The mean methyleneTHF value for the four treatment groups were 880, 1,769, 3,024 and 3,723 pmol/gww. Only half of the patients who received 60 mg/m(2) leucovorin had higher levels of methyleneTHF in tumour than patients who received 0 mg/m(2) leucovorin. Rectal cancer patients had significantly lower levels of methyleneTHF compared with colon cancer patients. CONCLUSIONS: There was a large inter-patient variability of tissue folate levels in colorectal cancer patients after supplementation with leucovorin at standardised dosage. High leucovorin doses were needed to exceed baseline methyleneTHF values, especially in rectal cancer patients. The results indicate that the standardised leucovorin dose may be insufficient to attain the full antitumour effect of 5-FU. Further studies are needed to establish whether higher dosage yields a better treatment response.

A survey of surgeons' perception and awareness of intraoperative time utilization.

BACKGROUND: Surgical teams' awareness of the time needed to perform specific phases of a surgical procedure is likely to improve communication in the operating theatre and benefit patient safety. The aim of this study was to assess surgeons' awareness of time utilization and the actual time needed to perform specific phases of an operation. METHODS: A survey was conducted to examine the method and design for a larger study. Interviews were conducted with 18 surgeons, and surgical time was measured during 21 colon cancer resections. Correlation analyses were performed to explore the factors that might affect operating time. RESULTS: The surgical phase with the greatest variation in time was dissection/resection (43-308 minutes). On a group level, no statistically significant differences were found between estimated and measured surgical procedural times for partial or full resections (160.4 versus 173.0 minutes, p = 0.539). However, interindividual variation was substantial. There was a positive significant correlation between long duration of dissection/resection and longer time to close the abdomen (r = 0.464, p = 0.039), as well as between long duration of a hand-sewn anastomosis and time needed to close the abdomen (r = 0.536, p = 0.018). CONCLUSIONS: It can be difficult for a single surgeon to estimate the time required for a partial or full surgical procedure. A larger study might provide additional time estimates and identify variables that affect surgical time. The data could be of interest in the planning and scheduling of surgical resources, thus improving theatre team communication and patient safety.

Thymidine phosphorylase expression is associated with time to progression in patients with metastatic colorectal cancer.

BACKGROUND: 5-Fluorouracil (5-FU) is the cornerstone of chemotherapeutic treatment for patients with colorectal cancer. The enzyme thymidine phosphorylase (TP) catalyzes the conversion of 5-FU to its active metabolite, 5-fluoro-2'-deoxyuridine. TP is expressed in tumour epithelial cells and stromal cells, particularly in tumour-associated macrophages. These macrophages may affect sensitivity to chemotherapy. Previously, we identified TP as a predictive factor in microdissected tumour samples of patients with advanced colorectal cancer. In the present study, we analysed TP expression in tissues and associated stromal cells from patients with advanced colorectal cancer and associated TP levels to tumour response and time-to-event variables during first-line chemotherapy treatment. We also investigated the association between serum TP levels at the time of surgery and gene expression in primary tumour tissues. METHODS: This study included 125 patients with metastatic colorectal cancer treated with first-line 5-FU-based chemotherapy. To quantify TP gene expression levels in tumour tissues, real-time polymerase chain reaction was performed using the 7500 Fast Real-Time PCR system (Applied Biosystems, Foster City, CA, USA). TP protein concentration in matched serum samples was determined using an enzyme-linked immunosorbent assay system (USCN Life Science Inc.). RESULTS: The tumour response rate was 31%, and 30% of patients exhibited stable disease. No associations between TP expression level and age or gender were observed. Levels of TP mRNA in mucosa and tumours were positively correlated (r = 0.41, p < 0.01). No correlation between TP expression and tumour response rate was observed. Time to progression was significantly longer in patients with high TP expression (p < 0.01). Serum TP protein levels were not associated with tumour response or time-to-event variables and did not correlate with gene expression in tumour tissues. CONCLUSIONS: High TP gene expression in non-microdissected tumour tissues of patients with advanced colorectal cancer correlates with longer time to progression, which could be related to treatment. These results are in contrast to previous studies where microdissected tumour cells were analysed and may be due to the presence of adjacent stromal cells. Serum TP protein expression does not correlate to TP gene expression in tissues of patients with advanced colorectal cancer.

Folate Levels and Polymorphisms in the Genes MTHFR, MTR, and TS in Colorectal Cancer.

AIM: The aim of the study was to explore and describe the effect of polymorphisms in folate-associated genes regarding the levels of different folate forms and their distribution in tumors and mucosa in patients with colorectal cancer. MATERIALS AND METHODS: Tumor and mucosa tissues from 53 patients with colorectal cancer were analyzed. The concentrations of tetrahydrofolate (THF), 5-methylTHF, and 5,10-methyleneTHF were measured by liquid chromatography-mass spectrometry. Genotyping of polymorphisms in the folate-associated genes methylenetetrahydrofolate reductase (MTHFR, C677T), methionine synthase (MTR, A2756G), and thymidylate synthase (TS, 5'-TSER 28 bp tandem repeat and 3'-TSUTR 6 bp deletion/insertion), were done by real-time polymerase chain reaction. Folate levels and distributions were determined in the total patient cohort and after subgrouping by genotypes. RESULTS: The total folate level, as well as the THF and 5,10-methyleneTHF levels, were significantly higher in the tumor compared with mucosa tissue (P = 0.030, 0.031, and 0.015, respectively). The individual variation in folate levels in both tumor and mucosa were larger than the variation found when the patients were subgrouped by the gene polymorphisms. No significant differences in the mean concentration of any folate in the mucosa or tumor tissue were found in relation to the analyzed polymorphisms. The percentage level of 5,10-methyleneTHF in tumors was highest in patients with the MTHFR 677 CC genotype, and lowest in patients with the TT genotype (P = 0.033). A significantly lower percentage level of the 5,10-methyleneTHF level was found in tumors of patients with the 5'-TSER 3R/3R genotype (P = 0.0031). CONCLUSION: A significant difference was found between the percentage level of 5,10-methyleneTHF in tumor tissues in relation to the MTHFR C677T and 5'-TSER 28 bp repeat polymorphisms. However, no differences were found in the actual tissue folate levels, or in their distribution, in relation to the polymorphisms in the MTHFR, MTR, or TS genes. These findings could be of importance for further research in the field by explaining some of the difficulties of obtaining reproducible and uniform results when using a few selected polymorphisms as predictive markers.

Changes in thymidine phosphorylase gene expression related to treatment of rectal cancer.

BACKGROUND: The enzyme thymidine phosphorylase (TYMP) has tumor-promoting functions and its expression is often elevated in tumors. PATIENTS AND METHODS: TYMP gene expression in tumorous and mucosal tissues was assessed using real-time polymerase chain reaction, in a study of patients with rectal cancer where chemotherapy and radiotherapy were given sequentially. RESULTS: TYMP levels decreased after chemotherapy. For patients given radiotherapy, there was a significant increase in TYMP expression comparing biopsies before and after radiotherapy. The increase was also observed in the mucosa, although it was less pronounced. CONCLUSION: Cancer treatment alters gene expression in tumor and adjacent mucosa of patients with rectal cancer. Chemotherapy may cause a decrease in TYMP gene expression, whereas radiotherapy, given as adjuvant treatment, causes a significant increase in expression. These results are of importance when interpreting TYMP expression data in rectal cancer and may be of clinical interest as TYMP participates in the activation of capecitabine.

Stage and size using magnetic resonance imaging and endosonography in neoadjuvantly-treated rectal cancer.

AIM: To assess the stage and size of rectal tumours using 1.5 Tesla (1.5T) magnetic resonance imaging (MRI) and three-dimensional (3D) endosonography (ERUS). METHODS: In this study, patients were recruited in a phase I/II trial of neoadjuvant chemotherapy for biopsy-proven rectal cancer planned for surgical resection with or without preoperative radiotherapy. The feasibility and accuracy of 1.5T MRI and 3D ERUS were compared with the histopathology of the fixed surgical specimen (pathology) to determine the stage and size of the rectal cancer before and after neoadjuvant chemotherapy. A Philips Intera 1.5T with a cardiac 5-channel synergy surface coil was used for the MRI, and a B-K Medical Falcon 2101 EXL 3D-Probe was used at 13 MHz for the ERUS. Our hypothesis was that the staging accuracy would be the same when using MRI, ERUS and a combination of MRI and ERUS. For the combination, MRI was chosen for the assessment of the lymph nodes, and ERUS was chosen for the assessment of perirectal tissue penetration. The stage was dichotomised into stage I and stage II or greater. The size was measured as the supero-inferior length and the maximal transaxial area of the tumour. RESULTS: The staging feasibility was 37 of 37 for the MRI and 29 of 36 for the ERUS, with stenosis as a limiting factor. Complete sets of investigations were available in 18 patients for size and 23 patients for stage. The stage accuracy by MRI, ERUS and the combination of MRI and ERUS was 0.65, 0.70 and 0.74, respectively, before chemotherapy and 0.65, 0.78 and 0.83, respectively, after chemotherapy. The improvement of the post-chemotherapy staging using the combination of MRI and ERUS compared with the staging using MRI alone was significant (P = 0.046). The post-chemotherapy understaging frequency by MRI, ERUS and the combination of MRI and ERUS was 0.18, 0.14 and 0.045, respectively, and these differences were non-significant. The measurements of the supero-inferior length by ERUS compared with MRI were within 1.96 standard deviations of the difference between the methods (18 mm) for tumours smaller than 50 mm. The agreement with pathology was within 1.96 standard deviations of the difference between imaging and pathology for all tumours with MRI (15 mm) and for tumours that did not exceed 50 mm with ERUS (22 mm). Tumours exceeding 50 mm in length could not be reliably measured by ERUS due to the limit in the length of each recording. CONCLUSION: MRI is preferable to use when assessing the size of large or stenotic rectal tumours. However, staging accuracy is improved by combining MRI with ERUS.

Long-term follow-up after preoperative chemotherapy using pemetrexed (Alimta) in rectal cancer.

AIM: To assess the long-term outcome in a cohort of patients treated with preoperative chemotherapy using pemetrexed (Alimta) for rectal cancer. PATIENTS AND METHODS: A prospective phase I/II study on preoperative chemotherapy using Alimta was conducted during 2006-2008. The long-term outcome was assessed here for both the study group (n=37) and the reference group (n=87). The focus was on cancer recurrence and survival with consideration of initial tumour stage and treatment response. RESULTS: There was one recurrence, each in stages I and II and three (23.1%) in stage III in the Alimta-treated group. One patient remains disease, free after surgery for metastasis. Patients with more symptoms remaining after treatment had a higher risk of recurrence. CONCLUSION: The initial Alimta study concluded that treatment was feasible in rectal cancer with significant reductions in tumour symptoms and size. The long-term outcome is acceptable and does not provide evidence against the concept of preoperative chemotherapy using Alimta.

Thymidine Phosphorylase Gene Expression in Stage III Colorectal Cancer.

BACKGROUND: The thymidine phosphorylase (TP) enzyme has several tumor-promoting functions. The aim of this study was to explore TP gene expression in relation to clinical and histopathological data obtained from patients with stage III colorectal cancer. METHODS AND RESULTS: TP gene expression was analyzed by real-time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene expression in tumors correlated with lymph node staging, with higher expression relating to a higher number of positive nodes and a worse N-stage. Higher TP expression was also associated with a worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared with patients having colon cancer. CONCLUSION: Higher intratumoral TP expression appears to be related to a worse N stage, and thus, with a worse prognosis. TP gene expression measured in a preoperative biopsy could be of interest in preoperative staging.

A study of aspects on gender and prognosis in synchronous colorectal cancer.

AIM: To assess differences in demography, pathology and prognosis with tumor multiplicity in colorectal cancer. METHOD: A retrospective single centre study of all patients surgically treated for a colorectal cancer during 1999-2008 (n = 2524). Patient characteristics, pathology and follow-up data were retrieved. Survival was assessed by overall and cancer specific survival. RESULTS: 60 (2.4%) patients had a synchronous cancer (SC), associated with right colon, higher age, more assessed lymph nodes but a lower frequency of stage III/IV disease (42% vs. 52%). There was no overall prognostic difference between single or multiple cancer patients but females with SC had better survival than corresponding males (P < 0.046). CONCLUSION: The incidence of synchronous cancers was 2.4% with the second cancer often located in right colon. The SC patients were older than single tumor patients, had a lower frequency of stage III/IV disease and the females with SC had a better survival prognosis than corresponding males.

Gene polymorphisms MTHFRC677T and MTRA2756G as predictive factors in adjuvant chemotherapy for stage III colorectal cancer.

BACKGROUND: The aim of this study was to explore the effect in stage III colorectal cancer of functional gene polymorphisms methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase (A2756G), in the folate metabolism on outcome and risk of toxicity for adjuvant chemotherapy. A secondary aim was to investigate any possible interdependency between the two genes. PATIENTS AND METHODS: one hundred and fifty randomly chosen patients with stage III colorectal cancer, treated with adjuvant chemotherapy, were genotyped by real-time PCR. Patient and treatment data were retrieved and assessed for demography, pathology, chemotherapy tolerability and survival after adjuvant therapy. The polymorphisms were studied separately and in combination to discover possible interactions. RESULTS: Patients with MTHFR 677 CC genotype carried lower risks of suffering from nausea (p=0.027), parasthesia (p=0.0042) and need for dose reduction (p=0.025). The CC genotype was also associated with better survival (p<0.034). There was interdependency with MTR A2756G. Patients with MTR AG/GG in combination with MTHFR CT/TT genotypes carried the highest risk of side-effects. CONCLUSION: Functional polymorphisms of MTHFR C677T and MTR A2756G can affect outcome and risk of toxicity during adjuvant chemotherapy in stage III colorectal cancer. Their possible interdependence brings attention to the function of folate metabolism overall regarding its association with 5-fluoruracil related toxicity. Our results could explain some of the difficulties of obtaining reproducible and uniform results when using single polymorphisms as predictive markers.

Variations in demography and prognosis by colon cancer location.

AIM: Tumours of the right and left colon are suggested to be different entities with different prognosis. The aim was to explore differences related to the location of a colonic tumour. PATIENTS AND METHODS: A single-centre retrospective analysis of all patients treated for colon cancer during 1999-2008 (n=1558) was carried out. Assessed data included demography, pathology and survival by cancer location, with left colon also sub-divided into left and sigmoid colon. RESULTS: Right colon carcinoma was associated with female gender, higher age and poor grade of differentiation; left colon carcinoma had characteristics of worse stages and requiring emergency surgery. Sigmoid tumours were of better grade and stage. Survival was related the staging, which varied with location. Right colon carcinoma conferred a worse overall survival (OS) (p<0.037) but not cancer-specific survival (CSS) or disease-free survival compared to the entire left colon, whilst sigmoid tumours conferred a better OS and CSS (p<0.001) when the left colon was sub-divided. CONCLUSION: There are differences in demography and pathology related to the location of colon cancer. Sigmoid location carries the best prognosis.

Age aspects of demography, pathology and survival assessment in colorectal cancer.

AIM: The aim of this study was to assess how age is related to differences in stage, tumour differentiation and treatment in colorectal cancer. PATIENTS AND METHODS: A retrospective study in a consecutive series of colorectal cancer patients (n = 2220) where age was related to demography, stage, tumour characteristics, treatment and outcome (OS/CSS) both as a continuous variable and grouped by high/low 10th percentiles, as young/old groups, with a third median reference group. RESULTS: Young patients had more advanced cancer stages (p = 0.012), higher N-status (p = 0.011) and more frequent T4/G4 tumours. Old patients had higher postoperative mortality and were less likely to receive chemotherapy. The proportion of cancer-related deaths was stage-dependent and decreased with age. CONCLUSION: Cancer stage, tumour characteristics, treatment and outcome can vary with age in colorectal cancer. The increasing proportion of non-cancer deaths at a higher age can affect the use of overall survival as an outcome parameter, which may be of importance in evaluating clinical and translational research.