Marc Winslet

Diet and colorectal cancer: implications for the obese and devotees of the Atkins diet

Colorectal cancer (CRC) is the second most common cause of cancer‐related death in the Western world and its prevalence is increasing. Potential causes of this increase are changes in diet and the increases in obesity seen. This paper looks at the literature surrounding diet and obesity and the links to this increase in CRC. Heralded as a weight loss miracle we investigate whether the literature suggests the Atkins diet may actually do more harm than good by acting to increase an individuals risk of CRC. Obesity has been demonstrated to be a major factor in the increase in CRC although links to changes in diet are more tenuous. Published studies on diet suggest the Atkins diet may help reduce rather than increase the risk of CRC.

Colon Carcinoma‐ Bugs, Bacterium and Bone Marrow

This edition of the Journal describes 3 of the more peripheral aspects of the investigation, management and prognosis of colorectal cancer, at least one of which is likely to be completely unknown to the majority of the readership. Mourra describes a case of rectal adenocarcinoma where initial metastatic work up was negative but a subsequent laparotomy a nodule under the capsule of the left lobe of the liver was identified and this was subsequently removed and found to be an asymptomatic infection by Linguatula serrata. The author notes that the presence of visceral pentastomiasis is not a contraindication to subsequent use of chemotherapy. It is fortuitous in this case the lesion was sub capsular as one wonders whether an infestation further within the liver substance would have resulted in the need for a formal resection to exclude the presence of occult metastasis and confirm the diagnosis of this spiny but benign parasite. On a more scientific note Altomare et al have evaluated the significance of the identification of pre operative non colon cancer stem cells in the bone marrow of patients subsequently undergoing an R0 resection. The authors have shown non colon cancer stem cells are not cancer cells and had no subsequent impact on liver metastases rates, cancer specific death rates or all death rates. In contrast, recent data in Nature has indicated that only colon cancer stem cells can metastasise. Their significance in bone marrow in the presence of an R0 resection remains to be determined. Finally Gupta et al provide a literature review on the significance of Streptococcus bovis in relation to colorectal cancer. The authors note that in the presence of S bovis bacteraemia a colonic neoplasm may be found in over 50% of cases, particularly if S bovis 1 is identified. On the basis of this the authors recommend evaluation for an occult neoplasm where appropriate and in light of the fact tumours have been reported years after an episode of S bovis endocarditis follow up colonoscopy should also be considered. They also note that the S bovis antigen profile may help distinguish those at high risk of having or developing colorectal cancer. The mechanism of this phenomenon is unknown but the authors postulate it may be mediated by inflammatory cytokines promoting premalignant lesions through the increased formation of hyperneoplastic aberrant crypts with associated vasodilatation and increased vascular permeability. A further association with liver disease and extra colonic malignancy serves only to increase the investigative burden associated organism. It is noteworthy that S bovis 2, rather appropriately named Streptococcus pasteurianus appears to exhibit a much weaker association!

Gastrointestinal Oncology: A Critical Multidisciplinary Team Approach

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Surveillance and screening for colorectal cancer: some answers and even more questions

This edition of the Journal includes a pivotal paper by Stupart et al from South Africa reporting their experience of surveillance colonoscopy in a cohort of subjects with the same single mismatch repair gene mutation. In 129 individuals with the mutation the incidence of colorectal cancer in the surveillance group was 11% vs 27% in nonsurveyed controls and tumours were also identified at an earlier age. The subsequent death rate was also reduced to 2% vs 12% in controls. This paper presents almost a unique human experiment in a relatively homogenous population which is unprecedented. The subsequent emphatic commentary from Dr Lindor confirms the importance of this paper in establishing a surveillance programme for Lynch Syndrome. The paper by Martellucci et al, however, describes the other end of the spectrum where there is marked patient heterogeneity. They report a series of 880 patients with colorectal cancer over 25 years in whom only one was subsequently diagnosed with familial adenomatous polyposis and two had classical mutations of hereditary non-polyposis colorectal cancer. In this clinical series, 36 patients were considered high risk based on early onset of tumour, multiple primaries and a high risk family history; these were referred for genetic testing. A further 15.9% had a first degree relative affected, 5.5% had tumour diagnosis at < 50 years and 15.2% in this series had multiple primaries which were synchronous metachronous or extra colonic. The authors comment that the incidence of hereditary colon cancer is low if only identified mutations are considered but the percentage quickly increases with marginal adjustment to identifying criteria. In contrast to the homogenous South African study the Italian group make a plea from the all too familiar real world where clinical suspicion seems more important than rigid criteria. Two further related papers of interest appear in the Journal. The first a rather worrying study from Peravali et al. where in a series of 348 patients with a carcinoma proximal to the splenic flexure who had imaging of the distal colon, only 20% had evidence of a distal neoplasm detected by flexible sigmoidoscopy and only 8% would have undergone a colonoscopy based on the UK flexible sigmoidoscopy trial protocol. At present colonoscopy after faecal occult blood testing remains the gold standard. This may change in the future however as highlighted by a paper from the Academic Surgical Unit in Hull comparing virtual (VC) and conventional colonoscopy in a prospective series of 150 patients. VC had 100% sensitivity and 99% specificity for carcinoma and proved to be the patient’s investigation of choice. The ‘completion rate’ for VC was 97% compared with the quoted figure of 75–90% for conventional colonoscopy. The authors also highlight the absence of morbidity, its value for staging and for identifying extra colonic findings which were present in up to 6%. The main limitations of VC appear to be with regard to flat polyps and its inability to provide a tissue diagnosis and therapeutic intervention. Total radiation exposure risk is less than that of a conventional barium enema. The results of this study are a compelling endorsement for virtual colonoscopy which in time may become the screening investigation of choice if issues regarding cost, availability and manpower can be met.

Lifestyle lavage and laxative abuse; with a nod to gemellus!

In the July 2009 edition of the Journal [1] Harris and the C-CLEAR group reported a systematic review and metaanalysis of prospective observational studies to quantify colorectal cancer risk associated with an increased BMI involving 67,361 incident cases. A higher BMI was associated with colon and rectal cancer in men but only colon cancer in women. Although increased BMI is associated with a modest increased risk the authors note that this may translate to large attributable proportions in high prevalence obese populations. This is important as such factors are modifiable for colorectal cancer prevention. Unfortunately the authors note that it remains to be seen whether reducing BMI will reduce cancer predisposition and allow formulation of appropriate public health strategies. In this edition of the Journal [2] the same group undertook a similar study to quantify gender specific risk associated with increased leisure time and physical activity, involving 7,873 incident cases. The authors identified an inverse association with colon cancer but not rectal cancer, although they noted that the benefits of less than the highest levels of LTPA may be small. The authors conclude that LTPA only intervention in cancer prevention is unlikely to impact substantially on incidence. In a further review in this edition [3] Seow Choen examines the claims of colonic hydrotherapy against known physiological facts. Advocates note that toxic overload in the colon may induce weight gain, fatigue, constipation, diarrhoea, mood swings, weakened immune system and stress. It is suggested hydrotherapy maybe of benefit in patients with allergies, arthritis, asthma, colonic stasis, bloating, candida, colitis in remission, constipation, diarrhoea, diverticulosis, flatulence, leaky gut, haemorrhoids, toxic headache, halitosis, indigestion, lethargy, mucous colitis, multiple sclerosis, parasitic infections, skin problems and urinary urgency! Seow Choen then provides a critique of the physiological basis for such claims referring to a formidable standard textbook of medical physiology, which struck fear in the heart of this editor as an undergraduate! The paper concludes there is no physiological basis for colonic hydrotherapy which may actually increase toxins and bacteria absorption and in unfortunate instances may result in rectal perforation, aplastic anaemia and disseminated abscess formation. Finally a case report in this edition indicates that melanosis coli from prolonged laxative abuse is reversible [4]. This editor is pleased to note that draconian measures to remove his middle-aged spread may have future benefits with regard to his predisposition to colon cancer but remains in a quandary as to whether to renew his annual gym membership in order to attain any further benefit from the highest levels of leisure time physical activity. He is relieved to acknowledge that the formidable tome which struck fear into his young heart during second MB provides a persuasive argument that his ongoing midlife co-morbidities may not require the services of an irrigationist and is reassured that any intermittent laxative use to regulate his profession induced colonic inertia will not result in lifelong mucosal stigmata. At present, however he will continue to rely on his low-dose aspirin and fish oil supplements as his only current lifestyle modification!

Evidence M’Lud: what evidence?

This edition of the Journal contains two major papers which merit comment. The first is a systemic review of the surgical management of anal fistulae by Malik and Nelson while the second is the National UK audit of PPH on behalf of the Association of Coloproctology of Great Britain and Ireland. Malik and Nelson note that anal fistulae have been documented as a surgical condition for over 2500 years and undertook a systematic review of all available randomised studies relating to the surgical management of this common condition. Their initial search strategy revealed 443 trials and two meta analyses with only 21 randomised trials considered valuable after predetermined exclusions. These trials consisted of comparisons in relatively small numbers describing a multitude of procedures from fistulotomy to fistulectomy, Seton insertion, mucosal flaps, advancement flaps and the use of glue. The authors note that the overall quality of the studies was poor with several sources of potential bias. Even the five RCTs of incision versus fistula surgery require cautious interpretation The authors conclude that in view of the small heterogeneous nature of the patient groups studied it is difficult to draw any strong inferences and note that even basic questions remained to be answered in the management including a consensus on study methodology defining the groups and outcome measures with minimum standards for follow-up. The National UK Audit of PPH reported by Knight et al. describes the electronic database established in 2005 to determine the indication and outcomes for PPH. Out of the 695 patients entered only 50% of them had grade III or IV haemorrhoids. This contrasts with the paper by Slawik published in 2007 where all patients in a series of 357 had grade 3 or 4 disease. Such patient selection may affect outcome in terms of postoperative symptoms such as urgency. It was also noted that the observed variation of the height of the staple line was 6 cm which is a highly unusual finding which the authors attribute to incorrect measurement from the anal verge. The audit highlights problems with data collection at a national level with only 10% of members contributing and the patient population accounting for only 20% of the staple guns purchased during the trial period. In the age of evidence based medicine these two important papers highlight the long road we are going to have to travel down to produce large volume, valid reproducible data on which to base our current practice.

A symptomatic second gallbladder 7 years post initial cholecystectomy

Sir, We report the case of a symptomatic second gallbladder 7 years post initial cholecystectomy. We believe this to be the first such case to be documented in the UK. Unusual anatomy of the biliary tree is well described, and can include multiple gallbladders. In fact, ‘normal’ biliary anatomy is only seen in 25% of the population. This is seldom clinically relevant and is usually a coincidental intraoperative finding. Very rarely, however, a duplicate gallbladder can cause symptoms after initial cholecystectomy, and may require further surgery 1. A 60-year-old gentleman presented with intermittent right upper quadrant pain. His symptoms were similar to those experienced 7 years previously when he was diagnosed with gallstones and gallbladder polyps on ultrasound scan. He had subsequently undergone an uncomplicated open cholecystectomy and histology reported a complete gallbladder (with stones) measuring 7×2×2 cm. The dissection was well described and no mention was made of unusual anatomy. Subsequent to his most recent presentation, an abdominal ultrasound scan revealed, surprisingly, a gallbladder containing polyps. This was confirmed on magnetic resonance cholangiopancreatography (Figure 1). The appearance was of a normally sized and positioned gallbladder with several polyps within. It was not buried in the liver. Figure 1.  Magnetic resonance cholangiopancreatography demonstrates a gallbladder containing polyps. He was reviewed by the professor of hepatopancreaticobiliary surgery who diagnosed a symptomatic missed duplicate gallbladder. The patients symptoms have since subsided and he declined further surgery. A rare but important cause of ongoing right upper quadrant pain in patients who have already undergone cholecystectomy is a symptomatic second gallbladder. This is the first such case reported in the UK but the phenomenon has been reported elsewhere. Surgeons should actively look for unusual anatomy at the time of initial cholecystectomy. We feel that some important learning points can be taken from this case: (1) ‘Unusual’ biliary anatomy is very common (25% of cases). (2) Efforts should be made at cholecystectomy to identify unusual anatomy. (3) Previous cholecystectomy does not rule out subsequent gallbladder disease.

Function vs fate

In this issue of the Journal Tilney and Tekkis present a literature review, as opposed to a quantitative metaanalysis, of 21 studies describing intersphincteric dissection for low rectal cancer. They report a leak rate of 10.5%, a local recurrence rate of 9.5% arguably influenced by lymph node positivity and an average 5-year survival of 81.5%. The authors note an expected significant reduction in resting anal pressure and a reported incidence of urgency of nearly 60% dependant on degree of sphincter excision. This figure may be improved by the construction of a synchronous colonic J Pouch. Whilst neoadjuvant chemotherapy may improve oncological outcome it may be at the cost of a poorer functional result. The authors suggest that in selected patients, particularly where the tumour is confined to the bowel wall, with appropriate counselling, the procedure is associated with acceptable oncological function outcome. In a subsequent commentary, Rullier cites further studies confirming a satisfactory oncological outcome. He then highlights the prerequisite of a safe circumferential resection margin, the poor oncological outcome after APER, independent of tumour stage and related to the risk of interoperative perforation and circumferential resection margin positivity (a risk further highlighted in the paper by Thompson et al. in this issue [3]) and the higher incidence of normal sexual function. It is noted that a comparatively low rate of recurrence after sphincter preservation may represent better anatomical definition and surgical specialization. It is fitting that approximately 100 years after the description of APER by Miles, with a better understanding of anatomical boundaries following the description of total mesorectal excision and improved surgical technique, sphincter preservation for all appropriate low rectal tumours in motivated patients may soon become the norm with an acceptable oncological outcome.