Individualized laparoscopic and related technique in rectal cancer surgery

[Extract from Preface] The main studies listed in each chapter were carefully selected as to reflect the critical knowledge essential in each of the important steps to overcome the main challenges toward the success in achieving the best possible outcomes in rectal cancer patient care. However, the main original contribution of the thesis was demonstrated clearly in "Chapter 3: Laparoscopic surgery for rectal cancer" where the proposed laparoscopic pull-through with coloanal anastomosis was highlighted. The chapter showed a prospective comparative study comparing all aspects of the two techniques; laparoscopic ultralow anterior resection versus laparoscopic pull-through with coloanal anastomosis for rectal cancers. All the published studies involved in each chapter of the thesis were carefully illustrated in their original format with my great respect to the international peer-review. Nevertheless, each chapter contained the overview aiming to state the connectivity of the ideas for each specific detail contained in each chapter. Despite the fact that the majority of the studies were conducted in high-volume, specialized centers, it was a real challenge to organize prospective studies for highly specific research questions over the limited time of my doctorate degree study. Chapter Overview. Chapter 1: Introduction. This chapter described the context of this research; why rectal cancer treatment is challenging; impact of multidisciplinary treatment on the outcomes. Chapter 2: Overview in colorectal cancer treatment. To review of role of various treatment modalities and variations to optimise both short-term and long-term outcomes; Hiranyakas A, Yik Hong H. Surgical Treatment of Colorectal Cancer – a Review. Int Surg. 2011; 96(2):120-6. Chapter 3: Laparoscopic surgery for rectal cancer. To discuss and propose appropriate laparoscopic techniques / approaches in the challenging surgical conditions to achieve the best possible outcomes; Hiranyakas A, Yik Hong H. Laparoscopic Ultralow Anterior Resection Versus Laparoscopic Pull-through with Coloanal Anastomosis for Rectal Cancers – a Comparative Study. Am J Surg. 2011; 202(3):291-7. Chapter 4: Factors influencing rectal cancer treatment outcomes. To discuss and propose the factors influencing the optimal outcomes for rectal cancer treatment; Hiranyakas A, Yik-Hong H, da Silva, GM, Wexner SD, Allende D, Berho M. Factors Influencing Circumferential Resection Margin in Rectal Cancer. Colorectal Dis. 2013 ;15(3):298-303. Chapter 5: Technique to avoid postsurgical complication. To discuss and propose surgical techniques essential in avoiding serious postsurgical consequences; Hiranyakas A, da Silva GM, Denoya P, Shawki S, Wexner SD. Colorectal Anastomotic Stricture: Is it associated with inadequate Colonic Mobilization? Tech Coloproctol. 2013 ;17(4):371-5. Chapter 6: Protocols for rapid recovery. To discuss in depth for the appropriate immediate postsurgical-care protocols to achieve the smooth and rapid recovery (among the most common diseased population); Hiranyakas A, Bashankaev B, Seo CJ, Khaikin M, Wexner SD. Epidemiology, Pathophysiology and Medical Management of Postoperative Ileus in the Elderly. Drugs Aging. 2011; 28(2):107- 18. Chapter 7: Closure of the ileostomy. To discuss and propose the necessity of certain surgical procedures to enhance optimal immediate postsurgical outcomes in low rectal cancer patients; Hiranyakas A, Rather A, da Sliva GM, Wexner SD, Weiss EG. Loop ileostomy Closure after Laparoscopic vs. Open Surgery: Is There a Difference? Surg Endosc. 2013 ;27(1):90-4. Chapter 8: Treatment of common stomal complication. To discuss and propose minimally invasive surgical approaches in the treatment of the common stomal consequence; Hiranyakas A, Yik Hong H. Laparoscopic Parastoma Hernia Repair, Multi-media Article. Dis Colon Rectum 2010; 53(9):1334-6. Chapter 9: Conclusion, outcomes and future research directions. This chapter gives the conclusions from the studies and proposes future research directions

The Impact of Rural-Urban Residency on Colorectal Cancer Screening, Stage at Diagnosis and Treatment in the Privately Insured Population

Colorectal Cancer (CRC) is the third most common and leading cause of cancer death in the United States. Although CRC screening can prevent and detect CRC at an early stage, about 35% of Americans are not screened. Despite the recent increase in screening, people with lower SES and those who live in rural areas have lowest screening. In rural areas, a common obstacle for screening is the long trips for health services which is associated with advanced CRC. Moreover, surgery is a substantial part of CRC treatment since stages I-III and some metastatic CRC (mCRC) patients are treated with surgery. Up to 25% of patients who undergo surgery get readmitted to the hospital due to several factors which costs $300 million annually. Prior studies showed some variations in CRC treatment between rural and urban patients. The purpose of this study was to assess the association between rural-urban status and CRC screening, stage at diagnosis and the receipt of CRC surgery. There were three specific aims: 1) To assess the impact of rurality on CRC screening, 2) To assess the impact of travel time on the stage of CRC diagnosis, and 3) To evaluate rural-urban differences in healthcare utilization. We conducted analyses using data from Blue Cross Blue Shield of Nebraska (BCBSNE) between 2012 and 2016. For Aim 1, the study population included BCBSNE members aged 50-64 years with average-risk CRC. For Aim2, the study population included BCBSNE members aged 50-64 years with average-risk CRC. For Aim 3, the study population consisted of CRC patients between the ages of 19-65 years old who had CRC surgery during the study period. Claims data were used to ascertain the CRC screening, diagnosis, receipt of surgery and hospital readmission using ICD and CPT codes. Rural-urban status was based on the Rural-Urban Commuting Area Codes and travel time between the residence and the provider facility was calculated using Google Map. For Aim 1, prevalence rates for FOBT and colonoscopy were calculated and compared using X2-test. Univariate and multivariate logistic regression analyses were performed to assess the relationship between the independent variables and CRC screening test. For Aim 2, we used Wilcoxon rank-sum tests for continuous variables and X2-tests for categorical variables and we adjusted for covariates using logistic regression. For Aim 3, Readmission and surgery status were estimated using multivariate logistic regression. There was no significant difference between rural and rural residents in colonoscopy use. However, after adjustment, rural residents were 47% more likely to use FOBT. Patients who do not use preventive services were 2.80 more likely to present with mCRC and urban residents were 3.50 times more likely to receive mCRC. The fact that 12% of our population presents with mCRC suggests some non-compliance with screening guidelines. Therefore, we recommend removing barriers that prevent rural patients from receiving screening colonoscopy and thus increase early detection of CRC. Until these obstacles have been lessened, screening with more convenient tests is encouraged. The use of mailed FOBT test is easy and more accessible

Reconstructive surgery:Risk factors, outcomes and advanced indications

The first part of this thesis investigates outcomes in reconstructive flap surgery using big data analysis. Firstly, outcomes after flap reconstructive surgery for diabetic patients compared to non-diabetic ones, highlighting higher risks of complications for diabetic patients, especially those with insulin-dependent diabetes. Additionally, it examines the impact of age and frailty on postoperative outcomes, emphasizing the importance of considering frailty scores instead of age alone in surgical planning for elderly patients. This thesis also delves into the incidence and risk factors of sepsis following reconstructive flap surgery, revealing significant associations with various patient factors. Moreover, racial disparities in outcomes after breast reconstructive surgery are explored, showing no differences in outcomes between different ethnicities. In the second part of this thesis, alternative surgical approaches for managing complications post-rectal/pelvic cancer surgery are discussed. These include the use of gluteal turnover flaps for perineal closure and a dorsal approach with partial sacrectomy followed by gluteal V-Y fasciocutaneous advancement flaps for treating chronic pelvic sepsis. Both techniques show promise in reducing complications and promoting wound healing. The effectiveness of gluteal fasciocutaneous flaps in treating chronic pelvic sepsis is highlighted specifically, offering a feasible and successful alternative for patients with limited options due to previous surgeries or (chemo)radiotherapy. Limitations of the studies, such as their retrospective nature and diverse patient populations, are acknowledged throughout

Reconstructive surgery:Risk factors, outcomes and advanced indications

The first part of this thesis investigates outcomes in reconstructive flap surgery using big data analysis. Firstly, outcomes after flap reconstructive surgery for diabetic patients compared to non-diabetic ones, highlighting higher risks of complications for diabetic patients, especially those with insulin-dependent diabetes. Additionally, it examines the impact of age and frailty on postoperative outcomes, emphasizing the importance of considering frailty scores instead of age alone in surgical planning for elderly patients. This thesis also delves into the incidence and risk factors of sepsis following reconstructive flap surgery, revealing significant associations with various patient factors. Moreover, racial disparities in outcomes after breast reconstructive surgery are explored, showing no differences in outcomes between different ethnicities. In the second part of this thesis, alternative surgical approaches for managing complications post-rectal/pelvic cancer surgery are discussed. These include the use of gluteal turnover flaps for perineal closure and a dorsal approach with partial sacrectomy followed by gluteal V-Y fasciocutaneous advancement flaps for treating chronic pelvic sepsis. Both techniques show promise in reducing complications and promoting wound healing. The effectiveness of gluteal fasciocutaneous flaps in treating chronic pelvic sepsis is highlighted specifically, offering a feasible and successful alternative for patients with limited options due to previous surgeries or (chemo)radiotherapy. Limitations of the studies, such as their retrospective nature and diverse patient populations, are acknowledged throughout

Position paper: management of perforated sigmoid diverticulitis

Peer reviewe

Volume 30, issue 5

The mission of CJS is to contribute to the effective continuing medical education of Canadian surgical specialists, using innovative techniques when feasible, and to provide surgeons with an effective vehicle for the dissemination of observations in the areas of clinical and basic science research. Visit the journal website at http://canjsurg.ca/ for more.https://ir.lib.uwo.ca/cjs/1219/thumbnail.jp

An investigation into the relationship between mode of presentation, clinicopathological factors and outcomes in colon cancer

Colorectal cancer is the 4th most common cancer in the United Kingdom and the second most common cause of cancer related death after lung cancer. Resectional surgery remains the cornerstone of treatment with curative intent however, despite this, a large proportion of patients eventually succumb due to recurrent or metastatic disease. Despite the widespread introduction of bowel cancer screening programmes, a significant proportion of cases of colorectal cancer continues to require investigation and treatment on an emergency basis. Emergency presentations have been reported to have significantly worse short-term and long-term outcomes than elective presentations even after adjustment for disease stage. It seems likely that as opposed to emergency presentations per se being associated with adverse outcomes in colorectal cancer, clinicopathological factors – tumour, host and other factors – are likely to be associated with emergency presentation and that it is these factors that are associated with adverse oncological outcomes. The work presented in this thesis examines the impact of emergency presentation on short-term and long-term outcomes of patients with colorectal cancer. It examines, in detail, the association between mode of presentation and tumour and host factors in patients undergoing treatment with curative intent for colon cancer and subsequently the association between these factors and long-term oncological outcomes. Chapter 1 provides an overview of colorectal cancer including epidemiology, risk factors, routes to presentation, presenting symptoms and signs and the investigation and management of patients with colorectal cancer. Chapter 2 examines 30 years of published literature in a systematic review and meta-analysis and summarises the existing literature regarding the association between mode of presentation and tumour and host factors in patients with colorectal cancer. The results conclude that there are multiple differences in tumour and host factors between elective and emergency presentations of colorectal cancer. However, the studies identified were heterogenous, and it was not possible to carry out a review of the effect of these factors on short-term and long-term outcomes. Chapter 3 examines the association between mode of presentation and basic clinicopathological factors within a regional cohort of patients presenting with colon or rectal cancer in the West of Scotland regardless of disease stage or treatment received. The results show that patients with colon cancer are more likely to undergo investigation and definitive treatment on an emergency basis in comparison to rectal cancer. Patients presenting emergently with colorectal cancer were more likely to have advanced disease at diagnosis. Furthermore, in a subgroup analysis of patients undergoing curative resectional surgery for TNM Stage I-III colon cancer, emergency presentation was associated with adverse short-term and long-term outcomes even after adjustment for disease stage. Chapter 4 examines the association between basic clinicopathological factors (tumour and host factors identified within Chapter 2), mode of presentation and short-term and long-term survival within a regional cohort of patients undergoing resectional surgery with curative intent for TNM I-III colon cancer. Younger age, increased comorbidity (as measured by ASA classification), lower BMI, more advanced T stage and extramural venous invasion were associated with both emergency presentation and with adverse oncological outcomes. However, emergency presentation remained independently associated with both adverse short-term survival and long-term oncological outcomes despite adjustment for these factors. Increased co-morbidity as measured by the Charlson Co-morbidity index was not associated with emergency presentation. When the association between mode of presentation and individual components of the Charlson Index was examined, only Diabetes Mellitus was associated with mode of presentation and was protective against emergency presentation. Within a subgroup analysis of patients with Diabetes Mellitus, no clear association between diabetic factors (Type 1 vs Type 2 Diabetes, type of diabetic control, metformin/sulfonylurea/insulin use) and mode of presentation was identified. Chapter 5 examines the association between the systemic inflammatory response, mode of presentation and short-term and long-term survival in a regional cohort of patients undergoing resectional surgery with curative intent for TNM I-III colon cancer. Both the neutrophil-lymphocyte ratio and the modified Glasgow Prognostic Score were independently prognostic and combined into a Systemic Inflammatory Grade. This Systemic Inflammatory Grade was independently associated with emergency presentation. When the association between clinicopathological factors, including mode of presentation and Systemic Inflammatory Grade, and short-term and long-term outcomes were analysed, Systemic Inflammatory Grade remained independently associated with short-term and long-term survival. Mode of presentation remained associated with short-term but not long-term survival. Chapter 6 examines the association between mode of presentation and CTderived body composition. High subcutaneous fat index and low skeletal muscle index were independently associated with emergency presentation and were associated with Systemic Inflammatory Grade even after adjustment for TNM Stage. Chapter 7 examines the prior interaction with the bowel screening programme of a regional cohort of patients diagnosed with colorectal cancer. Only 19% of patients were diagnosed through screening. Screening diagnosis was associated with significantly improved long-term outcomes. The most common reasons for failure to diagnosis through screening were non-invitation to screening (either above or below routine screening age), non-return of screening test (associated with male sex, increased socio-economic deprivation, increased comorbid status and current smokers) and negative screening test (associated with female sex, preoperative anaemia, less comorbid status, right-sided tumours and screening with gFOBT testing). Chapter 8 examines the association between tumour mutational status, mode of presentation and long-term outcomes in patients undergoing resectional surgery with curative intent for TNM I-III colon cancer. The results show that on unadjusted analysis, APC wild-type, KRAS mutant and BRAF wild-type colon cancer were associated with improved long-term outcomes. There may be an association between KRAS mutant status and an elevated systemic inflammatory response. On adjusted analysis, KRAS mutational status was independently associated with adverse long-term outcomes after adjustment for other clinicopathological factors. In this study, no statistically significant associations were seen between mutational status and mode of presentation however there were trends between P53 wild-type, KRAS mutant and PIK3CA mutant status and emergency presentation. Chapter 9 examines the association between the preoperative systemic inflammatory response, emergency presentation and short-term and long-term outcomes in patients undergoing resectional surgery with curative intent for TNM Stage II colon cancer when controlled for the established high-risk factors of TNM Stage II disease. The results show that after adjustment for these factors, emergency presentation was not independently associated with either shortterm or long-term outcomes however a significant association was seen between the preoperative systemic inflammatory response and outcomes. Chapter 10 presents the results from a national survey with regards to attitudes towards and the use of perioperative steroids in patients undergoing resectional surgery with colorectal cancer. The results show that perioperative steroids are widely used at the discretion of the anaesthetist with the primary aim of preventing postoperative nausea and vomiting. The results show that there is sufficient equipoise to carry out a randomised controlled trial examining the impact of single dose corticosteroid administration at induction of anaesthesia on the postoperative systemic inflammatory response and outcomes following colorectal resection

Assessment and optimisation of wearable activity monitors within an enhanced recovery framework

Enhanced recovery after surgery (ERAS) is a model of care that aims to improve patient recovery after surgery. Wearable activity monitors (WAMs) have the potential to provide possible solutions to a wide range of clinical challenges. The aim of this thesis was to assess whether physical activity, measured by a WAM, can be used as a measurable marker of peri-operative well-being and recovery after surgery, and whether the WAM can therefore be used to assess and help improve recovery after surgery. A wrist-worn WAM was utilised to measure physical activity in a healthy normal cohort showing that it was feasible to monitor continuous physical activity in a healthy cohort in a free-living environment. Activity data were processed both at an individual level and as a group allowing further analysis and comparator with the surgical patient cohort. The WAM was used to measure objective physical activity data for a cohort of patients undergoing colorectal surgery. Activity was assessed pre-operatively at home, post-operatively on the in-patient ward and then on discharge home back into the community. The physical activity data gave insight into patients’ baseline function and their progression and recovery following their surgical procedure, with more detailed analysis showing the WAM’s ability to reflect the daily activities on the ward. There were statistically significant correlations between peri-operative physical activity and post-operative outcomes. The results from the use of WAMs within this thesis provide an opportunity for refining the ERAS concept through continuous, objective physical activity monitoring as well as the potential to enhance patient/clinician communication, leading to more personalised care and an improvement in post-operative outcomes.Open Acces

Bioavailability of Omega-3 Fatty Acid Formulations and Their Effect on the Intestinal Microbiota

Due to their proposed anti-cancer effects, omega-3 fatty acids (O3FA) may have a role to play in both chemoprevention and the adjuvant treatment of colorectal cancer (CRC). Novel O3FA drink formulations may provide a more effective method of delivering O3FA supplementation, although O3FA bioavailability in these preparations compared to traditional capsules has not been ascertained. There is also a lack of research exploring the effects of O3FAs on the colonic microbiota and whether this may have any protective effect on CRC carcinogenesis. This thesis reports the findings of a randomised cross-over trial in healthy volunteers comparing the bioavailability of equivalent doses of O3FA supplementation (2g EPA and 2g DHA daily for 8 weeks) in capsule and drink carton formulations. The trial also explores the effects of O3FA on faecal microbiome profiles. In addition I report the analysis of red blood cell membrane (RBC) EPA levels from the previously reported EMT trial, a Phase II randomised, double-blind, placebo-controlled trial in which patients with colorectal cancer liver metastasis (CRCLM) received EPA (2g daily) prior to surgery. O3FA supplementation provided in a drinks carton supplementation was non-inferior to an equivalent dose of EPA and DHA provided in capsule form. Faecal microbiome profile analysis revealed subtle changes to the colonic microbiota including reversible increases to Lactobacillus and Bifidobacterium. Analysis of RBC samples from the EMT study revealed a positive correlation between RBC membrane and CRCLM tissue EPA levels. Participants with EPA RBC membrane levels of >1.22 also exhibited improved overall survival. This work provides evidence that an O3FA containing drink formulation is of equivalent bioavailability to traditional capsules. Due to their additional nutritional contents they may be of benefit in CRC patients. The effects of O3FAs on faecal microbiome profiles is of significant interest particularly their impact on bacteria associated with anti-CRC effects. Further work is required to elucidate whether O3FAs have a role in CRC chemoprevention or adjuvant treatment via their effects on the colonic microbiota.