Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Prerequisites to improve surgical cytoreduction in FIGO stage III/IV epithelial ovarian cancer and subsequent clinical ramifications.

BACKGROUND: No residual disease (CC 0) following cytoreductive surgery is pivotal for the prognosis of women with advanced stage epithelial ovarian cancer (EOC). Improving CC 0 resection rates without increasing morbidity and no delay in subsequent chemotherapy favors a better outcome in these women. Prerequisites to facilitate this surgical paradigm shift and subsequent ramifications need to be addressed. This quality improvement study assessed 559 women with advanced EOC who had cytoreductive surgery between January 2014 and December 2019 in our tertiary referral centre. Following implementation of the Enhanced Recovery After Surgery (ERAS) pathway and prehabilitation protocols, the surgical management paradigm in advanced EOC patients shifted towards maximal surgical effort cytoreduction in 2016. Surgical outcome parameters before, during, and after this paradigm shift were compared. The primary outcome measure was residual disease (RD). The secondary outcome parameters were postoperative morbidity, operative time (OT), length of stay (LOS) and progression-free-survival (PFS). RESULTS: R0 resection rate in patients with advanced EOC increased from 57.3% to 74.4% after the paradigm shift in surgical management whilst peri-operative morbidity and delays in adjuvant chemotherapy were unchanged. The mean OT increased from 133 + 55 min to 197 + 85 min, and postoperative high dependency/intensive care unit (HDU/ICU) admissions increased from 8.1% to 33.1%. The subsequent mean LOS increased from 7.0 + 2.6 to 8.4 + 4.9 days. The median PFS was 33 months. There was no difference for PFS in the three time frames but a trend towards improvement was observed. CONCLUSIONS: Improved CC 0 surgical cytoreduction rates without compromising morbidity in advanced EOC is achievable owing to the right conditions. Maximal effort cytoreductive surgery should solely be carried out in high output tertiary referral centres due to the associated substantial prerequisites and ramifications.

Clinical and oncological outcomes of pelvic exenteration surgery for anal squamous cell carcinoma.

AIM: Anal cancer incidence and mortality rates are rising in the United Kingdom (UK). Surgery is an important treatment modality for persistent or recurrent disease. There is a paucity of data on outcomes for patients undergoing pelvic exenteration for anal squamous cell carcinoma (SCC) for persistent or recurrent disease. The aim of this study was to investigate the outcomes for patients who were treated with pelvic exenteration for anal SCC from two high-volume, high-complexity pelvic exenteration units in the UK. METHOD: A retrospective review of prospectively maintained databases from 2011 to 2020 was undertaken. Primary endpoints included R0 resection rates, overall and disease-free survival at 2 and 5 years. RESULTS: From 2011 to 2020, 35 patients with anal SCC were selected for exenteration. An R0 resection was achieved in 26 patients (77%). Of the remaining patients, seven patients had an R1 resection and one had a R2 resection. One further patient was excluded from additional analysis as the disease was inoperable at the time of laparotomy. With a median follow-up of 19.5 months (interquartile range 7.9-53.5 months), overall survival was 50% (17/34). Patients with an R1/2 resection had a significantly poorer overall survival [0.27 (0.09-0.76), p = 0.021] than those patients in whom R0 resection was achieved. Disease-free survival was 38.2% (13/34) and an R1/R2 resection was associated with a significantly reduced disease-free survival [0.12 (0.04-0.36), p < 0.001]. CONCLUSION: Complete R0 resection for recurrent or persistent anal SCC is possible in the majority of patients and improves overall and disease-free survival compared with R1/R2 resection.

Pathway Of Low Anterior Resection syndrome relief after Surgery (POLARiS) feasibility trial protocol: a multicentre, feasibility cohort study with embedded randomised control trial to compare sacral neuromodulation and transanal irrigation to optimised conservative management in the management of major low anterior resection syndrome following rectal cancer treatment.

INTRODUCTION: Rectal cancer is common with a 60% 5-year survival rate. Treatment usually involves surgery with or without neoadjuvant chemoradiotherapy or adjuvant chemotherapy. Sphincter saving curative treatment can result in debilitating changes to bowel function known as low anterior resection syndrome (LARS). There are currently no clear guidelines on the management of LARS with only limited evidence for different treatment modalities. METHODS AND ANALYSIS: Patients who have undergone an anterior resection for rectal cancer in the last 10 years will be approached for the study. The feasibility trial will take place in four centres with a 9-month recruitment window and 12 months follow-up period. The primary objective is to assess the feasibility of recruitment to the POLARiS trial which will be achieved through assessment of recruitment, retainment and follow-up rates as well as the prevalence of major LARS.Feasibility outcomes will be analysed descriptively through the estimation of proportions with confidence intervals. Longitudinal patient reported outcome measures will be analysed according to scoring manuals and presented descriptively with reporting graphically over time. ETHICS AND DISSEMINATION: Ethical approval has been granted by Wales REC1; Reference 22/WA/0025. The feasibility study is in the process of set up. The results of the feasibility trial will feed into the design of an expanded, international trial. TRIAL REGISTRATION NUMBER: CT05319054.

Incorporating neoadjuvant chemotherapy into locally advanced colon cancer treatment pathways: Real-life experience of implementing FOxTROT.

AIM: The international FOxTROT trial, recently published in the Journal of Clinical Oncology is the first randomized controlled trial testing neoadjuvant chemotherapy (NAC) with oxaliplatin and 5-fluorouracil in locally advanced, but operable, colon cancer. The trial met its primary endpoint with fewer patients experiencing recurrent or residual disease at 2 years with NAC compared with the control (16.8% vs. 21.2%, risk ratio = 0.74, p  = 0.042). Translating the findings of the FOxTROT trial into improved patient outcomes is dependent on implementation of new neoadjuvant chemotherapy (NAC) pathways in colorectal cancer. METHOD: We describe our experience implementing a novel neoadjuvant treatment pathway in colorectal cancer at a large UK teaching hospital. RESULTS: To date 64 patients have been commenced on the novel pathway following presentation and adoption of the FOxTROT trial results. We present key lessons and strategies developed across the multidisciplinary team to minimize impact on person hours, service capacity and budget, whilst building patient safety and confidence. CONCLUSION: Use of NAC for locally advanced colon cancer has been shown to improve surgical outcomes and longer term cancer outcomes. Provision of NAC requires some modifications to current treatment pathways but can be delivered with team working and without the requirement for additional resources.

Rapid qualitative analysis in a mixed-methods evaluation of an infection prevention intervention in a UK hospital setting during the COVID-19 pandemic: A discussion of the CLEAN study methodology.

The COVID-19 pandemic created an urgent need for high-quality rapid research. One clinical challenge was how to minimise the risk of transmission in the hospital setting. The CLEAN study conducted a rapid evaluation of the potential utility of a spray-based disinfectant in a hospital setting. The study was undertaken between December 2020 and March 2021 and involved the implementation of the spray in 10 different clinical areas in one UK teaching hospital. A mixed-methods approach was adopted (including observations, surveys, and qualitative interviews) informed by the theories for understanding the implementation of new healthcare technologies. The evaluation found that while the spray had a number of perceived benefits when added to existing disinfection processes, other factors limited its potential utility. These findings informed a number of recommendations for future adoption within hospital settings. This paper describes and reflects on the rapid methodology that allowed us to undertake the study and deliver results in a short space of time. We experienced a number of pressures during set-up and fieldwork due to the challenging conditions caused by the pandemic, and the methodological approach had to evolve throughout the study because of the changing clinical context. The involvement of clinicians from the research setting as full members of the research team was key to the rapid delivery of the research. They provided an essential link to the implementation environment, and their experiential knowledge of the setting added an important perspective to the analysis. Balancing their involvement with their clinical roles was challenging, however, as was coordinating a large and diverse team of interviewers in such a short space of time. Overall, the study highlighted the value of rapid research to inform urgent healthcare decisions in a pandemic. Although our experience suggests that conducting such research requires some practical and methodological trade-offs, we found that there were also numerous benefits of using rapid methods and identified various opportunities to ensure their robustness.

Protocol: The role of defunctioning stoma prior to neoadjuvant therapy for locally advanced colonic and rectal cancer-A systematic review.

Defunctioning stomas (ileostomy and colostomy) may be used prior to commencement of neoadjuvant therapy in patients with locally advanced colon or rectal cancer, in order to prevent clinical large bowel obstruction caused by radiotherapy associated oedema or progression of disease in patients who are not obstructed. However, the exact rate of clinical obstruction in patients undergoing neoadjuvant therapy who do not receive a defunctioning stoma is not known. Furthermore, it is not clear which factors predispose patients to developing clinical large bowel obstruction. Given that defunctioning stomas are associated with post operative and intra-operative risks, it is not currently possible to tailor defunctioning stomas to patients who have the greatest risk of developing obstruction. This systematic review which is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA), aims to define the role of defunctioning stomas in prevention of obstruction patients with locally advanced colon or rectal cancer while undergoing neoadjuvant therapy. Two researchers will perform the literature search which will include all published and "in process" articles published in the English language between 2002-2022 in the following databases: EMBASE (OVID), MEDLINE (EBSCO), CINHAL complete, Web of Science, Cochrane Central Registry of Controlled Trials, Clinical Trials Registry. The full text of the selected articles will be independently screened by two researchers against the inclusion criteria. Data will be extracted from each article regarding: study design, participants, type of intervention and outcomes. The effect size will be expressed in incidence rates and when appropriate in relative risk with 95% confidence intervals. If possible, we will perform a meta-analysis. Heterogeneity will be assessed using I2 statistics. We will pool the data extracted from the randomised controlled trials to perform a meta-analysis using the Review Manager 5 software (RevMan 5). The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system will be used to assess the certainty of the evidence.

The management of retrorectal tumours: tertiary centre retrospective study.

AIM: Tumours of the retrorectal space are uncommon, pathologically heterogeneous, and difficult to diagnose, with ongoing controversy over their surgical management. The aim of this study was to evaluate the surgical management of a consecutive series of patients who had undergone excision of primary retrorectal tumours (PRRTs) at a tertiary referral centre. METHOD: Patients were identified from a prospectively maintained database between 1 March 2001 and 1 August 2021. Electronic patient records were reviewed for demographics, preoperative imaging, operative details, histology, and follow-up. A chi-squared test was used to assess the statistical significance of findings. RESULTS: A total of 144 patients were included in the study. Of these, 103 patients were female (71.5 per cent), 46 patients (31.9 per cent) presented incidentally, and 99 of the patients had tumours located below S3 (68.7 per cent). Overall, 76 patients underwent a transperineal approach (52.7 per cent) with the most common findings of a benign tailgut cyst occurring in 59 (40.9 per cent) of cases. Preoperative MRI predicted urovascular and pelvic sidewall involvement assessed intraoperatively with a sensitivity of 83.3 and 90 per cent and a specificity of 98.1 and 98 per cent respectively. Risk of malignancy in solid tumours was 31.4 versus 8.8 per cent in cystic tumours (relative risk 3.5, 95 per cent c.i. 1.6 to 7.6, P < 0.001). Major complications (Clavien-Dindo grade III and above) occurred in eight patients (5.6 per cent) and all-cause long-term mortality was 4.8 per cent (seven patients). DISCUSSION: PRRTs can be safely excised with minimal complications in specialized centres by surgical teams with the relevant expertise. This study questions the conservative management of cystic tumours and given the risk of solid tumour malignancy, supports surgical management.

The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review.

AIM: Anastomotic leak is the most feared complication of gastrointestinal surgery. Mesenchymal stem cell technology is used clinically to promote wound healing; however, the safety and efficacy of this technology on anastomotic healing has yet to be defined. The aim of this study was to investigate whether mesenchymal stem cells confer any benefit when applied to animal models for gastrointestinal anastomotic leak, identify the methodology and how efficacy is assessed. METHODS: The MEDLINE, EMBASE, WebofScience and Cochrane Library databases were interrogated between 1 January1947 to 1 May 2020. All studies where mesenchymal stem cells were applied to laboratory animal leak models to demonstrate a healing effect were considered. All experimental and histological outcomes were examined. Compliance to ARRIVE and current International Consensus was assessed. RESULTS: A total of 1205 studies were screened. Twelve studies reported on 438 gastrointestinal anastomoses in four species using 11 models; seven in the colon. No studies utilised a model with a known leak rate. Significant variance was observed in histological outcomes with efficacy demonstrated in five out of 12 studies. One study demonstrated a benefit in leak rate. Colorectal studies had a greater median ARRIVE compliance, 60.8% (IQR 63.2-64.5) compared to noncolorectal 45.4% (IQR 43.8-49.0). CONCLUSIONS: Mesenchymal stem cell delivery to an animal anastomosis is safe and feasible. Use may confer benefit but findings are currently limited to surrogate histological outcomes. There is consistency in outcome measures reported but variance in how this is assessed. Poor compliance to ARRIVE but good compliance to current international consensus in leak models of the colon was observed.

Colorectal cancer peritoneal metastases: Biology, treatment and next steps.

The presence of peritoneal metastases in patients with advanced colorectal cancer is associated with poor prognosis but the mechanisms for this are unclear. This review summarises the current knowledge of the pathophysiology, clinical features, prevalence, prognosis, and molecular biology of peritoneal metastases and the risk factors for the development of peritoneal metastases following resection of a primary colorectal tumour. Furthermore, the evidence for treatment strategies are described including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, early post-operative intraperitoneal chemotherapy, sequential post-operative intraperitoneal chemotherapy and emerging novel strategies. Active areas of research should include the identification of individuals at high risk of peritoneal metastases after curative resection of primary tumour, development of a surveillance program for high-risk patients, optimisation of systematic therapies and further investigation of the use of intraperitoneal chemotherapy.

A Review on the Scope of Photothermal Therapy-Based Nanomedicines in Preclinical Models of Colorectal Cancer.

Oncologic thermal ablation involves the use of hyperthermic temperatures to damage and treat solid cancers. Thermal ablation is being investigated as a method of treatment in colorectal cancers and has the potential to complement conventional anticancer treatments in managing local recurrence and metastatic disease. Photothermal therapy utilizes photosensitive agents to generate local heat and induce thermal ablation. There is growing interest in developing nanotechnology platforms to deliver such photosensitive agents. An advantage of nanomedicines is their multifunctionality, with the capability to deliver combinations of chemotherapeutics and cancer-imaging agents. To date, there have been no clinical studies evaluating photothermal therapy-based nanomedicines in colorectal cancers. This review presents the current scope of preclinical studies, investigating nanomedicines that have been developed for delivering multimodal photothermal therapy to colorectal cancers, with an emphasis on potential clinical applications.

Screening for colorectal cancer in defunctioned colons.

OBJECTIVES: Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons. METHODS: An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. RESULTS: Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area. CONCLUSIONS: Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

Uptake trends in the Scottish Bowel Screening Programme and the influences of age, sex, and deprivation.

Objective Age, sex, and deprivation are known factors influencing colorectal (bowel) cancer screening uptake. We investigated the influence of these factors on uptake over time. Methods Data from the Scottish Bowel Screening Programme (SBoSP) were collected between 2007 and 2014. End-points for analysis were uptake, faecal occult blood test positivity, and disease detection, adjusted for age, sex, deprivation, and year of screening. Results From 5,308,336 individual screening episodes documented, uptake gradually increased with increasing age up to 65-69 and was lower in men than women (52.4% vs. 58.7%, respectively). Deprivation had a significant effect on uptake by men and women of all age groups, with the most deprived least likely to complete a screening test. Uptake has increased with time in both sexes and across the deprivation gradient. The number needed to screen to detect significant neoplasia was significantly lower in men than women overall (170 vs. 365), and this held over all age and deprivation groups. The number needed to screen was also lower in the more deprived population. Conclusions Although lower age, male sex, and increased deprivation are associated with lower bowel cancer screening uptake in Scotland, uptake has increased since SBoSP introduction in all age groups, both sexes, and across the deprivation gradient. Despite a lower uptake, the number needed to screen to find significant disease was lower in men and in those with higher levels of deprivation.

Application of NICE guideline NG12 to the initial assessment of patients with lower gastrointestinal symptoms: not FIT for purpose?

Background The National Institute for Health and Care Excellence (NICE) published NG12 in 2015. The referral criteria for suspected colorectal cancer (CRC) caused controversy, because tests for occult blood in faeces were recommended. Faecal immunochemical tests for haemoglobin (FIT), which estimate faecal haemoglobin concentrations (f-Hb), might more than fulfil the intentions. Our aim was to compare the utility of f-Hb as the initial investigation with the NICE NG12 symptom-based guidelines. Methods Data from three studies were included. Patients had sex, age, symptoms, f-Hb and colonoscopy and histology data recorded. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of f-Hb and NG12 were calculated for all significant colorectal disease (SCD: CRC, higher risk adenoma and inflammatory bowel disease). Overall diagnostic accuracy was also estimated by the area under the receiver operating characteristic curve (AUC). Results A total of 1514 patients were included. At a cut-off of ≥10 µg Hb/g faeces, the sensitivity of f-Hb for CRC was 93.3% (95% confidence interval (CI): 80.7-98.3) with NPV of 99.7% (95%CI: 99.2-99.9). The sensitivity and NPV for SCD were 63.2% (95%CI: 56.6-69.4) and 96.0% (95%CI: 91.4-94.4), respectively. The NG12 sensitivity and NPV for SCD were 58.4% (95%CI: 51.8-64.8) and 87.6% (95%CI: 85.0-89.8), respectively. The AUC for CRC was 0.85 (95% CI: 0.87-0.90) for f-Hb versus 0.65 (95%CI: 0.58-0.73) for NG12 ( P < 0.005). For SCD, the AUC was 0.73 (95%CI: 0.69-0.77) for f-Hb versus 0.56 (95%CI: 0.52-0.60) for NG12 ( P < 0.0005). Conclusion f-Hb provides a good rule-out test for SCD and has significantly higher overall diagnostic accuracy than NG12.

Palliative Pelvic Exenteration: Clinical Outcomes and Quality of Life.

BACKGROUND: Locally advanced pelvic malignancy can be associated with disabling symptoms and reduced quality of life. If resectable with clear margins, a pelvic exenteration can offer long-term survival and improved quality of life. Its role in the palliation of symptoms has been described; however, the clinical outcomes and surgical indication are poorly defined. OBJECTIVE: This study describes the clinical and quality-of-life outcomes after palliative pelvic exenteration for advanced pelvic malignancy. DESIGN: Clinical data and patient-reported outcomes were collected for patients undergoing pelvic exenteration for symptom palliation. SETTINGS: This study was conducted at a tertiary referral center for pelvic exenteration. PATIENTS: All of the patients undergoing palliative pelvic exenteration for advanced primary rectal or recurrent cancer were included in our analysis. MAIN OUTCOME MEASURES: Patient-reported quality of life and physical and mental health status were measured. Quality-of-life trajectories were modeled over the 12 months from the date of surgery using linear mixed models. RESULTS: A total of 39 patients underwent pelvic exenteration for symptom palliation. Although there were no in-hospital deaths, 34% experienced significant morbidity. Patient-reported quality of life reduced postoperatively and gradually declined thereafter. Overall median survival was 24 months, with a 1-year mortality rate of 31%. There was a significant survival difference for the 39 patients undergoing pelvic exenteration compared with those patients who only had a debulking/bypass procedure or were closed without definitive treatment (overall median survival = 24 versus 9 months; p = <0.02). LIMITATIONS: Disease and patient heterogeneity limit the interpretation of these results. CONCLUSIONS: Palliative pelvic exenteration is a technically demanding operation that can be performed safely in a dedicated exenteration center. However, no durable palliation of symptoms with associated improved or sustained quality of life was observed, and the role of palliation therefore remains highly controversial in this complex group of patients.

Open versus laparoscopic right hemicolectomy in the elderly population.

AIM: To compare short term outcomes of elective laparoscopic and open right hemicolectomy (RH) in an elderly population. METHODS: All patients over the age of 70 undergoing elective RH at Ninewells Hospital and Perth Royal Infirmary between January 2006 and May 2011 were included in our analysis. Operative details, hospital length of stay, morbidity and mortality was collected by way of proforma from a dedicated prospective database. An extracorporeal anastomosis was performed routinely in the laparoscopic group. The primary endpoints for analysis were morbidity and mortality. Our secondary endpoints were operative duration, length of hospital stay and discharge destination. RESULTS: Two hundred and six patients were included in our analysis. One hundred and twenty-five patients underwent an open resection and 81 patients had a laparoscopic resection. The mean operating time was significantly longer in the laparoscopic group (139 ± 36 min vs 197 ± 53 min, P = 0.001). The mean length of hospital stay was similar in both groups (11.2 ± 7.8 d vs 9.6 ± 10.7 d, P = 0.28). The incidence of post-operative morbidities was 27% in the open group and 38% in the laparoscopic group (P = 0.12). Overall in-hospital mortality was 0.8% in open procedures vs 1% in laparoscopic. CONCLUSION: Laparoscopic RH was associated with a significantly longer operative time compared to open RH. In our study, laparoscopic RH was not associated with reduced post-operative morbidity or significantly shorter length of hospital stay.

Totally laparoscopic strategies for the management of colorectal cancer with synchronous liver metastasis.

INTRODUCTION: Laparoscopy is an accepted treatment for colorectal cancer and liver metastases, but there is no consensus for its use in the management of synchronous liver metastases (SCRLM). The purpose of this study was to evaluate totally laparoscopic strategies in the management of colorectal cancer with synchronous liver metastases. METHODS: Patients presenting to Ninewells Hospital between July 2007 and August 2010, with adenocarcinoma of the colon and rectum with synchronous liver metastases were considered. Patients underwent simultaneous laparoscopic liver and colon cancer resection, a staged laparoscopic resection of SCRLM and colon cancer, or simultaneous colon resection and radiofrequency ablation (RFA) of SCRLM. Primary endpoints were in-hospital morbidity and mortality, total hospital stay, intraoperative blood loss, duration of surgery, and resection margin status. RESULTS: Twenty-eight patients presented with synchronous colorectal liver metastases. Thirteen patients underwent a simultaneous laparoscopic liver and colon resection (median operating time, 370 (range, 190-540) min; median hospital stay, 7 (range, 3-54) days), seven patients had a staged laparoscopic resection of SCRLM and primary colon cancer (median operating time, 530 (range, 360-980) min; median hospital stay 14, (range, 6-51) days), and eight patients underwent laparoscopic colon resection and RFA of SCRLM (median operating time, 310 (range, 240-425) min; median hospital stay, 8 (range, 6-13) days). There were no conversions to an open procedure. Overall in-hospital morbidity and mortality was 28 and 0 % respectively. An R0 resection margin was achieved in 91 % of the resection group. At a median follow-up of 26 (range, 18-55) months, 19 (90 %) patients remain disease-free. CONCLUSIONS: Totally laparoscopic strategies for the radical treatment of stage IV colorectal cancer are feasible with low morbidity and favorable outcomes. A laparoscopic approach for the simultaneous management of SCRLM and primary colon cancer is associated with reduced surgical access trauma, postoperative morbidity, and hospital stay with no compromise in short-term oncological outcome.

Is familial adenomatous polyposis associated with sensorineural hearing loss?

Abstract The mutation causing familial adenomatous polyposis (FAP) affects the adenomatous polyposis coli (Apc) gene, which has a role in the cytoskeleton and has been shown to be important in the structure of supporting cells in the cochlea. One previous study suggested that FAP sufferers may have sensorineural hearing loss. In order to demonstrate whether this is the case we invited patients known to suffer from familial adenomatous polyposis to take part in our study. Audiograms were performed and compared to normal values for that patient's age and gender calculated using ISO standard data. Thirteen patients were included in the study analysis. No conductive hearing losses were identified. A statistically significant greater hearing loss was identified at 500 Hz (2.8 dBHL, P = 0.03) and 1000 Hz (2.5 dBHL, P = 0.05). No audiometric difference could be identified between the patients with FAP and attenuated FAP. A power calculation demonstrated that the study was of adequate size. This study did not demonstrate a clinically significant difference in hearing loss between the FAP group and the calculated normal values.

Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue.

The importance of asymmetric divisions for stem cell function and maintenance is well established in the developing nervous system and the skin; however, its role in gut epithelium and its importance for tumorigenesis is still debated. We demonstrate alignment of mitotic spindles perpendicular to the apical surface specifically in the stem cell compartments of mouse and human intestine and colon. This orientation correlates with the asymmetric retention of label-retaining DNA. Both the preference for perpendicular spindle alignment and asymmetric label retention are lost in precancerous tissue heterozygous for the adenomatous polyposis coli tumor suppressor (Apc). This loss correlates with cell shape changes specifically in the stem cell compartment. Our data suggest that loss of asymmetric division in stem cells might contribute to the oncogenic effect of Apc mutations in gut epithelium.

Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma.

BACKGROUND: The majority of patients with hilar cholangiocarcinoma have irresectable disease and require palliation with biliary stenting to alleviate symptoms and prevent biliary sepsis. Chemotherapy and radiotherapy have proved ineffective, but recent studies suggest photodynamic therapy (PDT) may improve the outlook for these patients. This prospective clinical cohort study has evaluated the efficacy of radical curative surgery, standard palliative therapy (stent +/- chemotherapy) and a novel palliative therapy (stent +/- Photofrin-PDT) in 50 consecutive patients treated for hilar cholangiocarcinoma over a 5-year period. METHODS: Between January 2002 and December 2006, 50 patients with hilar cholangiocarcinoma were evaluated for treatment. Ten patients were considered suitable for curative resection (Cohort 1). Forty patients with irresectable disease were stratified into Cohort 2 - Stent +/- chemotherapy (n= 17); and Cohort 3 - Stent +/- PDT (n= 23). Prospective follow-up in all patients and data collected for morbidity, mortality and overall patient survival. RESULTS: The median age was 68 years [range 44-83]. Positive cytology/histology was obtained in 28/50 (56%). One death in Cohort 1 occurred at 145 days after surgical resection. No treatment related-deaths occurred in Cohort 2 or 3, chemotherapy-induced morbidity in three patients in cohort 2, PDT-induced morbidity in 11 patients in cohort 3. Actual 1-year survival was 80%, 12% and 75% in Cohorts 1, 2 and 3, respectively. Mean survival after resection was 1278 days (median survival not reached). Mean and median survival was 173 and 169 days, respectively, in Cohort 2; and 512 and 425 days in Cohort 3. Patient survival was significantly longer in cohorts 1 and 3 (P < 0.0001; Log rank test). CONCLUSION: This prospective clinical cohort study has demonstrated that radical surgery and palliative Photofrin-PDT are associated with an increased survival in patients with hilar cholangiocarcinoma.