Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials.

BACKGROUND: This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS: A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS: In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION: This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS: A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS: A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION: NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

A European snapshot of psychosocial characteristics and patients' perspectives of faecal incontinence-do they correlate with current scoring systems?

PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.

Adenocarcinoma of the rectum in patients under age 40 is increasing: impact of signet-ring cell histology.

BACKGROUND: Overall, the incidence of colorectal cancer appears to be stable or diminishing. However, based on our practice pattern, we observed that the incidence of rectal cancer in patients under 40 is increasing and may be associated with a prominence of signet-ring cell histology. OBJECTIVE: The aim of this study was to verify the rising trend in rectal cancer in patients under 40 and describe the histology prominent in that cohort. DESIGN: This is a retrospective cohort study. SETTING AND PATIENTS: We performed a retrospective cohort study of all patients diagnosed with rectal adenocarcinoma from 1980 to 2010 using the Surveillance, Epidemiology, and End Results cancer registry. MAIN OUTCOME MEASURES: Rectal cancer incidence, histology, and associated staging characteristics were the primary outcomes measured. RESULTS: Although the incidence of rectal cancer for all ages remained stable from 1980 to 2010, we observed an annual percent change of +3.6% in the incidence of rectal cancer in patients under 40. The prevalence of signet cell histology in patients under 40 was significantly greater than in patients over 40 (3% vs 0.87%, p < 0.01). A multivariate regression analysis revealed an adjusted odds ratio of 3.6 (95% CI, 2.6-5.1) for signet cell histology in rectal adenocarcinoma under age 40. Signet cell histology was also significantly associated with a more advanced stage at presentation, poorly differentiated tumor grade, and worse prognosis compared with mucinous and nonmucinous rectal adenocarcinoma. LIMITATIONS: The study was limited by its retrospective nature and the information available in the Surveillance, Epidemiology, and End Results database. CONCLUSIONS: Despite a stable incidence of rectal cancer for all ages, the incidence in patients under 40 has quadrupled since 1980, and cancers in this group are 3.6 times more likely to have signet cell histology. Given the worse outcomes associated with signet cell histology, these data highlight a need for thorough evaluation of young patients with rectal symptoms.

Multicenter Evaluation of Rectal cancer ReImaging pOst Neoadjuvant (MERRION) Therapy.

OBJECTIVE: The aim of this study was to evaluate the utility of reimaging rectal cancer post-CRT (chemoradiotherapy) with magnetic resonance (MR) imaging of the pelvis for local staging and computed tomography of thorax, abdomen, and pelvis (CT TAP) to identify distant metastases. BACKGROUND: The success of neoadjuvant CRT for locally advanced rectal cancer has changed an already complex management algorithm. There is no consensus whether patients should be restaged before surgery. METHODS: Data from 5 institutions with prospectively maintained databases including patients who received neoadjuvant CRT for locally advanced rectal cancer were acquired. Only patients who had been staged pre- and post-CRT with MR imaging and CT TAP were included. MR findings were correlated with histopathological stage using weighted κ (kappa) statistics to test agreement, where a κ value of less than 0.5 was deemed unacceptable. RESULTS: A total of 285 patients fulfilled the criteria for the study; 84% had American Joint Committee for Cancer stage 3 disease pre-CRT, and the remainder had stage 2 disease. Fourteen patients did not proceed to surgery post-CRT-2 were observed as "complete responders," and the remainder either had unresectable disease or were unfit for surgery. MR imaging could not predict T stage (κ = 0.212) or nodal involvement (κ = 0.336). Most pertinently, MR imaging was unable to detect a complete pathological response (κ = 0.021), nor could it discriminate T4 disease (κ = 0.445). CT TAP restaging altered management in 6.7% of patients, who had metastatic disease. CONCLUSIONS: MR reimaging using standard protocols is of limited value in determining surgical approaches; a better modality of local restaging is required.

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.

Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

A virtual outpatient department provides a satisfactory patient experience following endoscopy.

PURPOSE: The purpose of this study was to investigate telephone follow-up of post-endoscopy patients as an alternative to attendance at the outpatient department. METHODS: Access to outpatient appointments is often a target for improvement in healthcare systems. Increased outpatient clinic capacity is not feasible without investment and extra manpower in an already constrained service. Outpatient attendance was audited at a busy colorectal surgical service. A subset of patients appropriate for follow-up in a "virtual outpatient department" (VOPD) were identified. A pilot study was designed and involved telephone follow-up of low-risk endoscopic procedures. Patient satisfaction was assessed using the Medical Interview Satisfaction Scale (MISS), which is a standardised survey of patient satisfaction with healthcare experiences. This was conducted via anonymous questionnaire at the end of the study. RESULTS: Of a total of 166 patients undergoing endoscopy in the time period, 79 were prospectively recruited to VOPD follow-up based on eligibility criteria. Overall, 67 (84.8 %) were successfully followed up by telephone consultation; nine patients (11.4 %) were contacted by mail. The remaining three patients (3.8 %) were brought back to the OPD. Patients recruited were more likely to be younger (55.82 ± 14.96 versus 60.78 ± 13.97 years, P = 0.029) and to have had normal examinations (49.4 versus 31.0 %, χ (2) = 5.070, P = 0.025). Nearly three quarters of patients responded to the questionnaire. The mean scores for all four aspects of the MISS were satisfactory, and overall patients were satisfied with the VOPD experience. CONCLUSION: VOPD is a target for improved healthcare provision, with improved efficiency and a high patient satisfaction rate.

Haemorrhoids and Anal Fissures in Pregnancy: Predictive Factors and Effective Treatments.

Introduction Haemorrhoids and anal fissures (HAF) are common in pregnancy and can severely affect the quality of life of those suffering from them. Despite the condition being common, there is limited evidence, formal guidelines or recommendations on treatment, and little is known about the natural course during pregnancy. Methods This was a prospective, observational cohort study conducted at a tertiary-referral university maternity hospital (The National Maternity Hospital, Dublin), conducted over a nine-month period. The first part of the study was a case-control study of antenatal patients over 34 weeks' gestation. The second part of the study involved a cohort of postnatal patients. Anonymous patient surveys were performed and analysed. Results Two hundred and fifty-eight patients were recruited into the study from the outpatient clinics and wards of one maternity hospital from April to December 2021. Of the antenatal patients, 82/184 (45%) of these patients had symptoms of HAF and 102/184 (55%) antenatal patients were unaffected, acting as controls. In addition, 74 affected postnatal patients were also included. In the affected antenatal group, 36/82 (44%) of patients had self-reported HAF (symptoms or signs of HAF); 50/82 (61%) of patients diagnosed with HAF on their own. 12/82 (15%) noticed symptoms in the first trimester, 25/82 (30%) in the second and 45/82 (55%) in the third. 142/184 (77%) of antenatal patients used conservative methods to manage their symptoms, including an increase in dietary fibre. 144/184 (78%) used medical treatments including suppositories. Only one patient had surgery. 70/156 (45%) of postnatal patients' symptoms resolved within days, 42/156 (27%) in weeks and 44/156 (28%) within months. Conclusion HAF affect almost half of the pregnancies. Age over 35 was significantly associated with antenatal haemorrhoids or anal fissures. Concerningly, the majority of patients (64%) self-diagnose and manage the condition without either seeking or receiving guidance from medical professionals. In terms of the natural course of the disease, it was encouraging that 45% of patients' symptoms resolved within a few days. This will help when counselling patients with distressing symptoms. Conservative measures such as increased dietary fibre, increased fluid intake and bath salts were effective in relieving symptoms for the majority of patients.

Surgical management strategies for colorectal malignancies of the splenic flexure - A systematic review and network meta-analysis.

BACKGROUND: Extended right hemicolectomy (ERHC) or left hemicolectomy (LHC) are accepted as the standard-of-care for colonic tumours of the splenic flexure. Lymphatic drainage at this site is poorly defined and subject to significant heterogeneity. Nevertheless, emerging evidence demonstrates the potential oncological safety of segmental splenic flexure colectomy (SFC). AIM: To perform a systematic review and network meta-analysis (NMA) to compare outcomes following ERHC, LHC and SFC for splenic flexure tumours (SFTs). METHODS: A systematic review was performed as per PRISMA guidelines. NMA was performed using R Shiny and Netmeta packages. RESULTS: A total of 13 studies, involving 6176 patients (ERHC n = 785; LHC n = 1527; SFC n = 3864) were included in the NMA. There was no difference in overall survival (OS) (SFC vs LHC Hazard Ratio [HR] 1.0, 95% Credible Interval [CrI] 0.76,1.34; SFC vs ERHC HR 1.18, 95% CrI 0.85,1.58) between the groups. SFC had a shorter operation time (Mean 176.37 min; Mean Difference [MD] SFC vs LHC 20.34 min 95% CrI 10.9, 29.97; SFC vs ERHC MD 22.19 95% CrI 11.09, 33.29) but also had a lower average lymph node yield (LNY) compared with ERHC (MD 7.15, 95% CrI 5.71, 8.60). ERHC had a significantly higher incidence of post-operative ileus (Odds Ratio [OR] 3.47, 95% CrI 1.11, 10.84). There was also no difference observed for minimally invasive approaches, anastomotic leak rate, perioperative mortality, reoperation rates or length of stay. CONCLUSIONS: While SFC may allow for reduced operative duration and improved bowel function postoperatively. SFC, LHC, ERHC are all acceptable approaches for curative resection of cancers of the splenic flexure, with no difference in OS observed. Thus, surgeon preference and candidate-specific factors will likely determine the management of SFTs.

Comparing minimally invasive surgical and open approaches to pelvic exenteration for locally advanced or recurrent pelvic malignancies - Systematic review and meta-analysis.

INTRODUCTION: Pelvic exenteration (PE) is a complex multivisceral surgical procedure indicated for locally advanced or recurrent pelvic malignancies. It poses significant technical challenges which account for the high risk of morbidity and mortality associated with the procedure. Developments in minimally invasive surgical (MIS) approaches and enhanced peri-operative care have facilitated improved long term outcomes. However, the optimum approach to PE remains controversial. METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines to identify studies comparing MIS (robotic or laparoscopic) approaches for PE versus the open approach for patients with locally advanced or recurrent pelvic malignancies. The methodological quality of the included studies was assessed systematically and a meta-analysis was conducted. RESULTS: 11 studies were identified, including 2009 patients, of whom 264 (13.1%) underwent MIS PE approaches. The MIS group displayed comparable R0 resections (Risk Ratio [RR] 1.02, 95% Confidence Interval [95% CI] 0.98, 1.07, p = 0.35)) and Lymph node yield (Weighted Mean Difference [WMD] 1.42, 95% CI -0.58, 3.43, p = 0.16), and although MIS had a trend towards improved towards improved survival and recurrence outcomes, this did not reach statistical significance. MIS was associated with prolonged operating times (WMD 67.93, 95% CI 4.43, 131.42, p < 0.00001) however, this correlated with less intra-operative blood loss, and a shorter length of post-operative stay (WMD -3.89, 955 CI -6.53, -1.25, p < 0.00001). Readmission rates were higher with MIS (RR 2.11, 95% CI 1.11, 4.02, p = 0.02), however, rates of pelvic abscess/sepsis were decreased (RR 0.45, 95% CI 0.21, 0.95, p = 0.04), and there was no difference in overall, major, or specific morbidity and mortality. CONCLUSION: MIS approaches are a safe and feasible option for PE, with no differences in survival or recurrence outcomes compared to the open approach. MIS also reduced the length of post-operative stay and decreased blood loss, offset by increased operating time.

Surgical approach for rectal cancer: A network meta-analysis comparing open, laparoscopic, robotic and transanal TME approaches.

BACKGROUND: The optimal approach for total mesorectal excision (TME) of rectal cancer remains controversial. AIM: To compare short- and long-term outcomes after open (OpTME), laparoscopic (LapTME), robotic (RoTME) and transanal TME (TaTME). METHODS: A systematic search of electronic databases was performed up to January 1, 2020 for randomized controlled trials (RCTs) comparing at least 2 TME strategies. A Bayesian arm-based random effect network meta-analysis (NMA) was performed, specifically, a mixed treatment comparison (MTC). RESULTS: 30 RCTs (and six updates) of 5586 patients with rectal cancer were included. No significant differences were identified in recurrence rates or survival rates. Operating time was shorter with OpTME (surface under the cumulative ranking curve [SUCRA] 0.96) compared to LapTME, RoTME and TaTME. Although OpTME was associated with the most blood loss (SUCRA 0.90) and had a slower recovery with increased length of stay (SUCRA 0.90) compared to the minimally invasive techniques, there was no difference in postoperative morbidity. OpTME was associated with a more complete TME specimen compared to LapTME (Risk Ratio [RR] 1.05, 95% Credible Interval [CrI] 1.01, 1.11), and TaTME had less involved CRMs (RR 0.173, 95% CrI 0.02, 0.76) versus LapTME. There were no differences between the modalities in terms of deep TME defects, DRM distance, or lymph node yield. CONCLUSIONS: While OpTME was the most effective TME modality for short term histopathological resection quality, there was no difference in long-term oncologic outcomes. Minimally invasive approaches enhance postoperative recovery, at the cost of longer operating times. Technique selection should be based on individual tumour characteristics and patient expectations, as well as surgeon and institutional expertise.

Patient satisfaction with a multidisciplinary colorectal and urogynaecology service.

INTRODUCTION: Traditionally, the pelvic floor has been described as three separate compartments and problems in each compartment were managed separately. A more contemporary approach is to identify the entire pelvic floor as a single dynamic compartment. Multidisciplinary pelvic floor clinics such as ours with the support of physiotherapy, clinical nurse specialists, urodynamics, and endo-anal ultrasound are uncommon. The aim of this study was to assess patient satisfaction with a joint colorectal and urogynaecology clinic. METHOD: All women who attended our service in 2015 were identified. Women who saw both a colorectal surgeon and urogynaecologist at the same clinic were included. The Satisfaction with Outpatient Services questionnaire, a multi-dimensional outpatient survey, was mailed to all women. RESULTS: A total of 364 new women attended our service in 2015. One hundred thirty-six (35.2%) saw both a colorectal surgeon and urogynaecologist at the same visit. There was a 64% (87/136) response rate to the questionnaire. Overall, all questions regarding their attendance were responded to positively by 94% (82/87) of women. Confidence and trust in the doctor examining and treating them was reported by all women. Seeing multiple specialists was of benefit to 97% (84/87) of women and 94% (82/87) would recommend the Pelvic Floor Centre. CONCLUSION: There is a high level of satisfaction amongst women attending our outpatient service. Being seen by multiple specialities at a single clinic was felt to be of benefit by the majority of women and all expressed physician confidence. Our multidisciplinary service may reduce waiting times, increase satisfaction, and is likely cost-effective.

Intraoperative frozen section assessment of sentinel lymph nodes in the operative management of women with symptomatic breast cancer.

BACKGROUND: Maximisation of the potential of sentinel lymph node biopsy as a minimally invasive method of axillary staging requires sensitive intraoperative pathological analysis so that rates of re-operation for lymphatic metastases are minimised. The aim of this study was to describe the test parameters of the frozen section evaluation of sentinel node biopsy for breast cancer compared to the gold standard of standard permanent pathological evaluation at our institution. METHODS: The accuracy of intraoperative frozen section (FS) of sentinel nodes was determined in 94 consecutive women undergoing surgery for clinically node negative, invasive breast cancer (37:T1 disease; 43:T2; 14:T3). Definitive evidence of lymphatic spread on FS indicated immediate level II axillary clearance while sentinel node "negativity" on intraoperative testing led to the operation being curtailed to allow formal H&E analysis of the remaining sentinel nodal tissue. RESULTS: Intraoperative FS correctly predicted axillary involvement in 23/30 patients with lymphatic metastases (76% sensitivity rate) permitting definitive surgery to be completed at the index operation in 87 women (93%) overall. All SN found involved on FS were confirmed as harbouring tumour cells on subsequent formal specimen examination (100% specificity and positive predictive value) with 16 patients having additional non-sentinel nodes found also to contain tumour. Negative Predictive Values were highest in women with T1 tumours (97%) and lessened with more local advancement of disease (T2 rates: 86%; T3: 75%). Of those with falsely negative FS, three had only micrometastatic disease. CONCLUSION: Intraoperative FS reliably evaluates the status of the sentinel node allowing most women complete their surgery in a single stage. Thus SN can be offered with increased confidence to those less likely to have negative axillae hence expanding the population of potential beneficiaries.

Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer.

Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.

Lynch syndrome: an updated review.

Lynch syndrome is one of the most common cancer susceptibility syndromes. Individuals with Lynch syndrome have a 50%-70% lifetime risk of colorectal cancer, 40%-60% risk of endometrial cancer, and increased risks of several other malignancies. It is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. In a subset of patients, Lynch syndrome is caused by 3' end deletions of the EPCAM gene, which can lead to epigenetic silencing of the closely linked MSH2. Relying solely on age and family history based criteria inaccurately identifies eligibility for Lynch syndrome screening or testing in 25%-70% of cases. There has been a steady increase in Lynch syndrome tumor screening programs since 2000 and institutions are rapidly adopting a universal screening approach to identify the patients that would benefit from genetic counseling and germline testing. These include microsatellite instability testing and/or immunohistochemical testing to identify tumor mismatch repair deficiencies. However, universal screening is not standard across institutions. Furthermore, variation exists regarding the optimum method for tracking and disclosing results. In this review, we summarize traditional screening criteria for Lynch syndrome, and discuss universal screening methods. International guidelines are necessary to standardize Lynch syndrome high-risk clinics.

Catheter associated blood stream infections in patients receiving parenteral nutrition: a prospective study of 850 patients.

BACKGROUND: Data was prospectively collected on 850 consecutive patients undergoing central venous catheterisation (CVC) to receive total parenteral nutrition (TPN) in a major university teaching hospital over a 46 months period. METHODS: Data included information about CVC insertion and clinical outcomes, most notably, suspected catheter-related blood stream infections (CRBSI). RESULTS: The internal jugular vein was the most common site (n = 882, 68%), followed by the subclavian vein (n = 344, 24.6%) and femoral vein (n = 95, 6.5%). The CRBSI rate per 100 line feeding days was 0.93% in patients cared for in a non ICU setting versus 1.98% for ICU managed patients. The mean number of line days preceding a pyrexial spike was 13.1. CRBSI was commonest in patients with femoral lines (n = 21/95, 22.1%), especially those cared for in a non-ICU setting (29.6% versus 14.5% for those in the ICU group). Preference should be given to internal jugular or subclavian-sited CVCs in ICU and non-ICU patients to reduce the risk of CRBSI. If femoral catheterisation is unavoidable, strict attention to aseptic technique is mandatory. CONCLUSION: The aim of this study was to investigate the rate and pattern of CRBSI and to recommend changes in protocol, technique and equipment as deemed necessary from these findings.

Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer.

The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic epithelium and lost in colon cancer, but its exact role on a molecular level and within the carcinogenesis pathway is yet to be described. Epidemiologic studies show that inadequate dietary calcium predisposes to colon cancer; this may be due to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR expression does not seem to be an early event in carcinogenesis; indeed it is associated with late stage, poorly differentiated, chemo-resistant tumors. Induction of CaSR expression in neoplastic colonocytes arrests tumor progression and deems tumors more sensitive to chemotherapy; hence CaSR may be an important target in colon cancer treatment. The CaSR has a complex role in colon cancer; however, more investigation is required on a molecular level to clarify its exact function in carcinogenesis. This review describes the mechanisms by which the CaSR is currently implicated in colon cancer and identifies areas where further study is needed.

The role of thrombomodulin in malignancy.

More than 150 years ago, Trousseau first suggested a link between cancer and thrombosis. Although this link has been widely described subsequently, the underlying mechanism still remains unclear. Thrombomodulin (TM), a natural endothelial anticoagulant, has proved itself to be an exciting molecule of many functions, not least of those in inflammation, thrombosis, and carcinogenesis. It has been highlighted and supported in many studies as having a cytoprotective role in many types of carcinoma; however, the mechanism of this role remains undefined. It is clear that TM exerts an influence on the endothelium and on the metastatic capacity of cancer, with elevated TM expression conferring a positive predictive and prognostic factor. Exactly how TM features in the metastatic pathway is unclear; however, once this has been clearly outlined, the opportunities afforded by inducers of TM expression may provide potential therapies to improve tumor behavior and impede transendothelial spread of cancer.

Screening for abdominal aortic aneurysms in cardiovascular patients.

BACKGROUND: The objective of the study was to determine the incidence of Abdominal Aortic Aneurysms (AAA) in a population of symptomatic cardiac patients. A retrospective cohort study of investigations was done at the cardiology clinic, Beaumont Hospital, Dublin. MATERIALS AND METHODS: There were 415 men and women recruited by referral to the cardiology clinic. All participants underwent routine ultrasound screening for AAA, and full assessment of all cardiac risk factors. Data were analyzed and correlated with age, sex, and diagnosis. RESULTS: Ultrasonographic diagnosis of aneurysm was based on an anteroposterior diameter of 3 cm or more. Of the 415 patients screened, 47 aneurysms were detected. Total incidence of AAA was 9.9% (male 14.1%, female 3.95%). All aneurysms were detected in patients over 60 years, detection rate 11.7% (male 16.3%, female 3.9%). The incidence of AAA was significantly higher in those who were subsequently proven to have cardiovascular disease, 13.8% (male 18%, female 5.15%). CONCLUSION: Screening the general population for those at risk of AAA is an ongoing debate. This study supports the concept of screening a higher risk population of patients over 60 years with cardiovascular disease.