A. Craig Lynch

Faecal diversion in the management of perianal Crohn’s disease

Aim  Severe perianal Crohn’s disease remains an uncommon but important indication for faecal diversion (FD). The advent of biological therapy such as infliximab for Crohn’s disease is considered to have improved the outcome for these patients. The aim of this study was to assess the outcome of patients undergoing FD for perianal Crohn’s disease and the impact of biological therapy (infliximab).

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A systemic review

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit.

INFLAMMATORY BOWEL DISEASE AND THE LUNG: IS THERE A LINK BETWEEN SURGERY AND BRONCHIECTASIS?

PurposeOne-third of patients with inflammatory bowel disease (IBD) has extracolonic manifestations. Inflammatory bowel-associated pulmonary disease is one of the less commonly recognized and more recently described manifestations. Here, we report the experience of our patients with inflammatory bowel-associated bronchiectasis.MethodsA retrospective analysis of case notes of patients with IBD and respiratory manifestations was undertaken. Relevant demographic, clinical, radiological, and pulmonary physiology laboratory results were reviewed.ResultsTen patients with IBD and bronchiectasis were identified. Eight developed respiratory symptoms after surgery for IBD. Five of the ten had ulcerative colitis. Their lung function abnormality is mild to moderate in severity. Small airways disease (forced expiratory flow between 25–75% is <50%) was evident in seven of the ten patients.ConclusionsThis preliminary study supports an association between surgery for IBD and development of symptomatic lung disease, particularly bronchiectasis, in susceptible patients. The pulmonary manifestations of IBD in some patients may only become clinically significant after surgery and the withdrawal of medical treatment.

Anastomotic Leaks After Restorative Resections for Rectal Cancer Compromise Cancer Outcomes and Survival.

BACKGROUND: Anastomotic leaks after restorative resections for rectal cancer may lead to worse long-term outcomes. OBJECTIVE: The purpose of this study was to evaluate the best current evidence assessing anastomotic leaks in rectal cancer resections with curative intent and their impact on survival and cancer recurrence. DATA SOURCES: A meta-analysis was performed using MEDLINE, EMBASE, and Cochrane search engines for relevant studies published between January 1982 and January 2015. STUDY SELECTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was used to screen and select relevant studies for the review using key words “colorectal surgery; colorectal neoplasm; rectal neoplasm” and “anastomotic leak.” INTERVENTION: Anastomotic leak groups were compared with nonanastomotic leak groups. MAIN OUTCOME MEASURES: ORs were calculated from binary data for local recurrence, distant recurrence, and cancer-specific mortality. A random-effects model was then used to calculate pooled ORs with 95% CIs. RESULTS: Eleven studies with 13,655 patients met the inclusion criteria. This included 5 prospective cohort and 6 retrospective cohort studies. Median follow-up was 60 months. Higher cancer-specific mortality was noted in the leak group with an OR of 1.30 (95% CI, 1.04–1.62; p < 0.05). Local recurrences were more likely in rectal cancer resections complicated by anastomotic leaks (OR = 1.61 (95% CI, 1.25–2.09); p < 0.001). Distant recurrence was not more likely in the anastomotic leak group (OR = 1.07 (95% CI, 0.87–1.33); p = 0.52). LIMITATIONS: All 11 studies are level 3 evidence cohort studies. Additional sensitivity analyses were performed to minimize cross-study heterogeneity. CONCLUSIONS: Anastomotic leaks after restorative resections for rectal cancer adversely impact cancer-specific mortality and local recurrence.

Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention

Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets.

Systematic Review of FDG-PET Prediction of Complete Pathological Response and Survival in Rectal Cancer

AbstractBackgroundAdvances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of 18F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. MethodsA search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. ResultsSeventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). ConclusionSUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of 18F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer.

This study aims to evaluate the feasibility and outcomes of intraoperative radiotherapy (IORT) using high‐dose‐rate (HDR) brachytherapy for locally advanced or recurrent rectal cancers. Despite preoperative chemoradiation, patients with locally advanced or recurrent rectal cancers undergoing surgery remain at high risk of local recurrence. Intensification of radiation with IORT may improve local control.

Acute and chronic pseudo‐obstruction: a current update

Acute colonic pseudo‐obstruction (ACPO) and chronic intestinal pseudo‐obstruction (CIPO) are distinct clinical entities in which patients present similarly with symptoms of a mechanical obstruction without an occlusive lesion. Unfortunately, they also share the issues related to a delay in diagnosis, including inappropriate management and poor outcomes. Advancements have been made in our understanding of the aetiologies of both conditions. Several predisposing factors linked to critical illness have been implicated in ACPO. CIPO is a functional motility disorder, historically misdiagnosed, with unnecessary surgery being performed in many patients with dire consequences. This review discusses the pathophysiology, clinical and diagnostic features, and treatment of each. For ACPO, a safer pharmacological approach to treatment is presented in a modified up‐to‐date algorithm. The importance of CIPO as a differential diagnosis when seeing patients with recurrent admissions for abdominal pain and distention is also discussed, as well as specific indications for surgery. While surgery is often a last resort, the role of the surgeon in the management of both ACPO and CIPO cannot be undervalued. By characterizing each condition in a common review, the knowledge gleaned aims to optimize outcomes for these frequently complex patients.

Thromboprophylaxis among Australasian colorectal surgeons.

Thromboembolism is a common cause of morbidity and mortality in patients with colorectal cancer, but thromboprophylaxis (TP) is underutilized. Current guidelines do not make specific recommendations for colorectal cancer patients and provide minimal guidance for the ambulatory setting, although emerging evidence suggests TP may be warranted during chemoradiotherapy or in the extended post‐operative phase. A survey of Australasian colorectal surgeons was therefore performed to assess current TP practice and attitudes.

Preoperative staging of rectal cancer

Preoperative staging is now an essential factor in the multidisciplinary management of rectal cancer because tumor stage is the strongest predictive factor for recurrence. Preoperative staging of rectal cancer can be divided into either local or distant staging. Local staging incorporates the assessment of mural wall invasion, circumferential resection margin involvement, as well as the nodal status for metastasis. Distant staging assesses for evidence of metastatic disease. The aim of this review is to consider the indications and limitations of the current preoperative imaging modalities for rectal cancer staging including clinical examination, endorectal ultrasound, magnetic resonance imaging, computed tomography and positron emission tomography-computed tomography, with respect to local and distant disease.