Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways

The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity.

see more @  Hagland HR, Søreide K. Cellular metabolism in colorectal carcinogenesis:

Influence of lifestyle, gut microbiome and metabolic pathways. Cancer Lett. 2014 
Mar 12. pii: S0304-3835(14)00133-5. doi: 10.1016/j.canlet.2014.02.026.

Defining CIMP in epigenetics - a walk in the park?

Defining CIMP for correct classification of epigenetically altered tumors can be a challenging task, yet correct classification is very important for understanding tumor biology, identifying molecular classes that can explain differences in outcome or response to therapy, and for comparison between results from different groups.

We have recently added to the debate by comparing a set of commonly agreed panels to assess CIMP. The discrepancy between some of the markers and panels - and, depending on the number of genes and the number of probes in each gene included - was considerable and (maybe) even disturbing!

read the full text paper published in Plos One, if you would like to read beyond the abstract:

PLoS One. 2014 Jan 21;9(1):e86657. doi: 10.1371/journal.pone.0086657. eCollection 2014.

Comparison of CpG Island Methylator Phenotype (CIMP) Frequency in Colon Cancer Using Different Probe- and Gene-Specific Scoring Alternatives on Recommended Multi-Gene Panels.

Berg M1, Hagland HR2, Søreide K3.


Abstract

BACKGROUND:

In colorectal cancer a distinct subgroup of tumours demonstrate the CpG island methylator phenotype (CIMP). However, a consensus of how to score CIMP is not reached, and variation in definition may influence the reported CIMP prevalence in tumours. Thus, we sought to compare currently suggested definitions and cut-offs for methylation markers and how they influence CIMP classification in colon cancer.

METHODS:

Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), with subsequent fragment analysis, was used to investigate methylation of tumour samples. In total, 31 CpG sites, located in 8 different genes (RUNX3, MLH1, NEUROG1, CDKN2A, IGF2, CRABP1, SOCS1 and CACNA1G) were investigated in 64 distinct colon cancers and 2 colon cancer cell lines. The Ogino gene panel includes all 8 genes, in addition to the Weisenberger panel of which only 5 of the 8 genes included were investigated. In total, 18 alternative combinations of scoring of CIMP positivity on probe-, gene-, and panel-level were analysed and compared.

RESULTS:

For 47 samples (71%), the CIMP status was constant and independent of criteria used for scoring; 34 samples were constantly scored as CIMP negative, and 13 (20%) consistently scored as CIMP positive. Only four of 31 probes (13%) investigated showed no difference in the numbers of positive samples using the different cut-offs. Within the panels a trend was observed that increasing the gene-level stringency resulted in a larger difference in CIMP positive samples than increasing the probe-level stringency. A significant difference between positive samples using 'the most stringent' as compared to 'the least stringent' criteria (20% vs 46%, respectively; p<0.005) was demonstrated.

CONCLUSIONS:

A statistical significant variation in the frequency of CIMP depending on the cut-offs and genes included in a panel was found, with twice as many positives samples by least compared to most stringent definition used.

Freebies from the BJS: Emergency surgery issue launched hot from the press!!!

Now it is available for access and free download: The themed Emergency surgery issue is now published on the BJS website and can be searched up in Pubmed.

Go to this link to access the content!

Have a Merry Xmas everyone!!!

Volume 101 Issue 1 (January 2014)

Leading articles

Improving outcomes in emergency surgery 

• Author:A. Bergenfelz, K. Søreide
• Published: Nov 27, 2013
• Pages: e1-e2

Barriers, regulations and solutions in emergency surgery research 

• Author:T. J. Coats
• Published: Nov 25, 2013
• Pages: e3-e4

Checklists and crisis management in surgical emergencies 

• Author:K. Ram, M. A. Boermeester
• Published: Nov 13, 2013
• Pages: e5-e6

Organization of emergency surgery 

• Author:A. Leppäniemi
• Published: Nov 13, 2013
• Pages: e7-e8

Reviews

Global disease burden of conditions requiring emergency surgery 

• Author:B. Stewart, P. Khanduri, C. McCord, M. Ohene‐Yeboah, S. Uranues, F. Vega Rivera, C. Mock
• Published: Nov 25, 2013
• Pages: e9-e22

Commentary

Global disease burden of conditions requiring emergency surgery ( Br J Surg 2014; 101: e9–e22) 

• Author:R. T. Petroze
• Published: Dec 12, 2013
• Pages: e23-e23

Reviews

Contemporary management of abdominal surgical emergencies in infants and children 

• Author:L. W. E. van Heurn, M. P. Pakarinen, T. Wester
• Published: Nov 29, 2013
• Pages: e24-e33

Multidisciplinary management strategies for acute non‐variceal upper gastrointestinal bleeding 

• Author:Y. Lu, R. Loffroy, J. Y. W. Lau, A. Barkun
• Published: Nov 26, 2013
• Pages: e34-e50

Strategies to improve the outcome of emergency surgery for perforated peptic ulcer 

• Author:K. Søreide, K. Thorsen, J. A. Søreide
• Published: Nov 29, 2013
• Pages: e51-e64

Staged multidisciplinary step‐up management for necrotizing pancreatitis 

• Author:D. W. da Costa, D. Boerma, H. C. van Santvoort, K. D. Horvath, J. Werner, C. R. Carter, T. L. Bollen, H. G. Gooszen, M. G. Besselink, O. J. Bakker
• Published: Nov 22, 2013
• Pages: e65-e79
• 
  

  Natural orifice transluminal endoscopic surgery for intra‐abdominal emergency conditions 

  • Author:J. Bingener, I. Ibrahim‐zada
  • Published: Nov 25, 2013
  • Pages: e80-e89

  Minimally invasive and surgical management strategies tailored to the severity of acute diverticulitis 

  • Author:F. D. McDermott, D. Collins, A. Heeney, D. C. Winter
  • Published: Nov 21, 2013
  • Pages: e90-e99

  Modern treatment of acute mesenteric ischaemia 

  • Author:S. Acosta, M. Björck
  • Published: Nov 20, 2013
  • Pages: e100-e108

  Damage control surgery for abdominal emergencies 

  • Author:D. G. Weber, C. Bendinelli, Z. J. Balogh
  • Published: Nov 25, 2013
  • Pages: e109-e118

  Early diagnosis of necrotizing fasciitis 

  • Author:T. Goh, L. G. Goh, C. H. Ang, C. H. Wong
  • Published: Nov 29, 2013
  • Pages: e119-e125

  Systematic Review

  Systematic review of emergency laparoscopic colorectal resection 

  • Author:D. P. Harji, B. Griffiths, D. Burke, P. M. Sagar
  • Published: Nov 28, 2013
  • Pages: e126-e133

  Original Articles

  A traffic‐light coding system to organize emergency surgery across surgical disciplines 

  • Author:A. Leppäniemi, I. Jousela
  • Published: Nov 22, 2013
  • Pages: e134-e140

  Effect of the introduction of an emergency general surgery service on outcomes from appendicectomy 

  • Author:K. Suen, I. P. Hayes, B. N. J. Thomson, S. Shedda
  • Published: Nov 25, 2013
  • Pages: e141-e146

  Accuracy of MRI compared with ultrasound imaging and selective use of CT to discriminate simple from perforated appendicitis 

  • Author:M. M. N. Leeuwenburgh, M. J. Wiezer, B. M. Wiarda, W. H. Bouma, S. S. K. S. Phoa, H. B. A. C. Stockmann, S. Jensch, P. M. M. Bossuyt, M. A. Boermeester, J. Stoker, 
  • Published: Nov 22, 2013
  • Pages: e147-e155

  Spectrum of oesophageal perforations and their influence on management 

  • Author:S. Wahed, B. Dent, R. Jones, S. M. Griffin
  • Published: Nov 22, 2013
  • Pages: e156-e162

Abdominal emergencies in children - free paper

Please access this link to read the full text paper on "Contemporary management of acute abdominal emergencies in infants and children" just published in the BJS and free to access online.

The paper deals with update info on acute appendicitis, hernia, intestinal malrotation and/or strangulation, pyloric stenosis, intussusception and a handful of other conditions that may present to the general surgeon on call.

Illustration of malrotation, from the paper by van Heurn and colleagues in the BJS. Source: 
British Journal of Surgery 29 NOV 2013 DOI: 10.1002/bjs.9335http://onlinelibrary.wiley.com/doi/10.1002/bjs.9335/full#bjs9335-fig-0001

Coming up: Emergency surgery issue in the BJS

A collective sieries on emergency surgery conditions will be launched in the January issue of the BJS. All papers will be free to access, either via PubMed searches or direct through the BJS website (or, most conveniently probably by downloading the BJS app for iPad, makes it easier to read on your tablet).

A leader to introduce the series has recently been launched and can be accessed here.

I will try to introduce some of the papers as they are real eased early online - I believe there are plenty material that will be of great use and interest to a worldwide readership.

Excited to have your response as we go!

Cheers,

Kjetil

Centenary Talks given at ASGBI, Glasgow and ACS, Washington 2013

Related to the BJS centenary a symposium was held at the International Surgical Congress of the Associations of Surgeons of Great Britain & Ireland in Glasgow, May 2013. You can find all the lectures to the ASGBI 2013 BJS Symposium: 100 years of BJS by going to the BJS website.

Also, a co-anniversary was held in Washington DC, marking the 100 years of both the BJS and the American College of Surgeons. The symposium can be view in entirety here.

International collaboration in surgical research: Lancet paper

I very recently had the privilege to be leading a group of authors under the acronym IRIS working group (Int'l Research collaboration In Surgery) to produce a report on the current state of research collaboration across borders in surgery and suggestions as to how this can be improved for the future.
Considering the huge number of surgeries performed worldwide each year - it is estimated at 245 million operations, and not taking into account that a large part of surgeons' work consists also of non-operative management of surgical disease - the number of patients that are accrued or contributing to trials is a mere minimum, likely far below 1% of all surgeries performed.

In the paper it is being discussed the different types of strategies that can be explored to increase collaboration and involvement in research for surgeons. Obviously this is but a starting point and there is a lot more to be said and even more to be done to rectify the current state of surgical trial activity.

You can read the full paper at the Lancet or search the reference at the bottom page here.

Please do get in contact should you have any ideas or would like to get involved from your part in this.
You can send me any note (or request for the full paper) through this link.

The Lancet, Volume 382, Issue 9898, Pages 1140 - 1151, 28 September 2013, doi:10.1016/S0140-6736(13)61455-5.

Lymph nodes in colon cancer

For patients undergoing curative resections for colon cancer, the nodal status (presence or not of metastatic cells in the lymph nodes) represents the strongest prognostic factor, yet at the same time it is one of the most disputed issues as well in colorectal cancer staging. We have investigated this topic over the past several years (see references 1-6 listed below).

You can read the fulltext article on qualitative and quantitative aspects of lymph nodes in colon cancer here.

reproduced from Veen et al. Dig Surg, 2013

As a consequence of this ongoing dispute, the qualitative and quantitative aspects of lymph node evaluation are being scrutinized beyond the blunt distinction between 'node positive' (pN+) and 'node negative' (pN0) disease. 

Controversy ranges from a minimal or 'least-unit' strategy as exemplified by the 'sentinel node' (see f.ex. reference 3 below) to a maximally invasive or 'all inclusive' approach by extensive surgery. 
Ranging between these two extremes of node sampling strategies are factors of quantitative and qualitative value, which may be subject to modification. 

reproduced from Veen et al. Dig Surg, 2013.

Qualitative issues may include aspects of lymph node harvest reflected by surgeon, pathologist and even hospital performance, which all may be subject to modification. However, patient's age, gender and genotype may be non-modifiable, yet influence node sample. 

Quantitative issues may reflect the balance between absolute numbers and models investigating the relationships of positive to negative nodes (lymph node ratio; log odds of positive lymph nodes).

Read the full text article (link is available above) and let me know your opinion on this!

1: Berg M, Guriby M, Nordgård O, Nedrebø BS, Ahlquist TC, Smaaland R, Oltedal S, 
Søreide JA, Kørner H, Lothe RA, Søreide K. Influence of microsatellite
instability, KRAS and BRAF mutations on lymph node harvest in stage I-III colon
cancers. Mol Med. 2013 Aug 21. doi: 10.2119/molmed.2013.00049. [Epub ahead of
print] PubMed PMID: 23979710. 

2: Veen T, Nedrebø BS, Stormark K, Søreide JA, Kørner H, Søreide K. Qualitative
and Quantitative Issues of Lymph Nodes as Prognostic Factor in Colon Cancer. Dig Surg. 2013 Apr 10;30(1):1-11.  


3: Nordgård O, Oltedal S, Aasprong OG, Søreide JA, Søreide K, Tjensvoll K, Gilje 
B, Heikkilä R, Guriby M, Lothe RA, Smaaland R, Kørner H. Prognostic relevance of 
occult metastases detected by cytokeratin 20 and mucin 2 mRNA levels in sentinel 
lymph nodes from colon cancer patients. Ann Surg Oncol. 2012 Nov;19(12):3719-26. 
doi: 10.1245/s10434-012-2454-8. Epub 2012 Jul 3. PubMed PMID: 22752373. 


4: Søreide K. Lymph node evaluation for colon cancer. JAMA. 2011 Dec
28;306(24):2669; author reply 2669. doi: 10.1001/jama.2011.1882. PubMed PMID:
22203534. 


5: Nedrebø BS, Søreide K, Nesbakken A, Eriksen MT, Søreide JA, Kørner H;
Norwegian Colorectal Cancer Group. Risk factors associated with poor lymph node
harvest after colon cancer surgery in a national cohort. Colorectal Dis. 2013
Jun;15(6):e301-8. doi: 10.1111/codi.12245. PubMed PMID: 23582027. 


6: Søreide K, Nedrebø BS, Søreide JA, Slewa A, Kørner H. Lymph node harvest in
colon cancer: influence of microsatellite instability and proximal tumor
location. World J Surg. 2009 Dec;33(12):2695-703. doi: 10.1007/s00268-009-0255-4.
PubMed PMID: 19823901.

BJS news: new website, new app and the newest impact factor!

IF is out today and BJS is climbing! Although not yet back at the all-time-high in 2008 (at 4.921) it is currently at 4.839.

We are now second overall! (Only after Annals - which continues to decrease considerably, from 7.49 to 6.33 = biggest drop in the category!).

Excluding the others in the "surgery" category (some of which are really not competitors, such as Am J Surg Pathol, Endoscopy and Am J Transplant):

Third place is held by JACS (steady from last year at 4.5),
Surg Obest Rel Dis has increased to 4.12
Ann Surg Oncol, steady at 4.12
Archives declined from 4.4 to 4.1
Surgery declined to 3.3….etc etc

This just to give a few details form the surgical field of the IF.

Good thing is that we are among the very few top surgical journals with an increase (and in IF, when several others see no progress or even continued decline! For what it' worth (yes, IF is not everything) I think it is a sign of the efforts put into the Journal (I hope).

Next year we'll break the 5.0 barrier!

And... the newly refreshed web-page of the BJS is out, please click here for a view!

Finally, and a much awaited tool for BJS readers, is the new BJS app for iPad, which is downloadable at the BJS homepage, or through this link here.

Frontiers | Using Patient-Reported Outcome Measures for Improved Decision-Making in Patients with Gastrointestinal Cancer – the Last Clinical Frontier in Surgical Oncology? | Frontiers in Surgical Oncology

Frontiers | Using Patient-Reported Outcome Measures for Improved Decision-Making in Patients with Gastrointestinal Cancer – the Last Clinical Frontier in Surgical Oncology? | Frontiers in Surgical Oncology