Thread: Pla Som : Fish delicacy Thai villagers relish can be deadly

I guess I owe a few apologies, I kind of forgot about the rest of you on this thread when I went for guyinthailand and derailed the thread, which is disrespectful to you. But having git start quoting from papers which were dependent upon established technologies which he absolutely believes cannot and do not work; is a little to much for me to ignore. I was really hoping to get him to see the inconsistency in using conclusions to support his arguments, that have been obtained using methodologies which he absolutely believes don't work. I was toying with the idea of using some of the pathological thinking that dentists use and let him rip me for doing so. But then with ENT turning up I started to think may be this would be trolling, kind of made it put up or shut up time.

What I have said is an opinion based on a body of evidence I dug up as part of a review in to the subject a few years ago. for various reasons including TD posting rules, i cannot post it, but I have gone back to my notes and references and I will give a summary below, It is based on research current in 2010.

I will assume that everyone, who is sane, is happy that pcr, elisa/western blot tests are diagnostic and that the link between this fluke and certain types of cancer is proven.

There are two broad paths that O. viverrini is believed to cause cancer in humans:

• It excretes a potent growth factor
• It provokes the immune system creating a cronic inflammatory response

O. viverrini though out its life excretes a partially potent growth factor which mimics a human growth factor that is implicated in a number of human cancers[1]. The growth factor cases wide ranging changes in gene expression[2,3]

O. viverrini excretes a number of compounds which cause a heightened immunise response to the presence of the fluke[4]. The immunse response causes inflammation, fibrosis, scaring, lesions[4]. This damage exploses the surrounding cells to DNA damage caused to radicals realised by the cronic inflammatory response and exposed to nitrosal compounds [5] contained many fermented and preservered foods. There is evidence that chronic inflamitary responses can be self perpetrating [6]


My take on this evidence and the rest was that the fluke infection created an environment within the bile ducts which was conducive to cancer formation. The rapid cell division, the gene expression changes, the cronic inflammation and the physical and DNA damage that this causes. Finally, and I think most importantly, this physical damage, which will persist, enhances the cells exposure to food born nitrosal compounds further damaging the cells DNA. Maybe I am reading too much into this, but that first infection creates long term sensitivity to food born carcinogens and I recon thats the key, perhaps with genetic predispotion, to determine who and who will not develop cancer.

right or wrong... I will take it on the chin without posting random statements of faith or going off to sulk and pretend it didn't all happen.

If I am correct, here are some predictions

• I would expect that people who have been infected with O. viverrini and then move and change diet to one which is low in nitrosal exposure should suffer less cancer or vis versa when compared to those stayed put.
  
• You would also expect to see the CCA cancer rates to see a long delay between the drop in infection rates and the coniquental drop in CCA rates. because although people less people were exposed to the fluke, all things being the same their exposure to food born nitrosal compounds would remain unchanged.
  
• If nitrosal exposure is a necessary co factor with O. viverrini infection, you would expect to see inconsistencies between O. viverrini and CCA rates where the local exposure to nitrosal compounds is low compared with surrounding areas.

Ive not seen any studies which would prove or disprove either of these predictions. no doubt GIT will have a good look around and save me the trouble.

[1]
A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells, Michael J. Smout, Thewarach Laha, Jason Mulvenna, Banchob Sripa, Sutas Suttiprapa, Alun Jones, Paul J. Brindley and Alex Loukas, PLoS Pathog. 2009 October; 5(10), e1000611


[2] Gene expression profiling defined pathways correlated with fibroblast cell proliferation induced by Opisthorchis viverrini excretory/secretory product, Chanitra Thuwajit, Peti Thuwajit, Kazuhiko Uchida, Daoyot Daorueang, Sasithorn Kaewkes, Sopit Wongkham, Masanao Miwa, World J Gastroenterol 2006 June 14;12(22):3585-3592

[3] GENES AND CHOLANGIOCARCINOMA, Kanlayanee Sawanyawisuth, SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH, 2009, 40(4), 701-712

[4] Localisation of parasite antigens and inflammatory responses in experimental opisthorchiasis, Banchob Sripaa, Sasithorn Kaewkesb, International Journal for Parasitology
Volume 30, Issue 6, 1 May 2000, Pages 735–740

[5] Exposure to N-nitroso compounds in a population of high liver cancer regions in Thailand: volatile nitrosamine (VNA) levels in Thai food, Mitacek EJ, Brunnemann KD, Suttajit M, Martin N, Limsila T, Ohshima H, Caplan LS., Food Chem Toxicol. 1999 Apr;37(4):297-305

[6] Promoter hypermethylation is a major event of hMLH1 gene inactivation in liver fluke related cholangiocarcinoma, Temduang Limpaiboona, Prasong Khaenama, Patcharee Chinnasria, Montisha Soonklanga, Patcharee Jearanaikoona, Banchob Sripac, Chawalit Pairojkulc, Vajarabhongsa Bhudhisawasdid, Cancer Letters Volume 217, Issue 2, 20 January 2005, Pages 213–219

[7] The Single Exposure Carcinogen Database, Calabrese EJ, Blain RB., Toxicol Sci. 1999 Aug;50(2):169-85.

Hazz

I for one do not argue with the studies you cite -its the conclusion that you draw that I am add odds with. Nobody doubts that CCA occurs as the result of a number of factors -fluke, nitro compounds, immune response and even mechanical damage. BUT - the conclusion you draw is at odds with the epidemiology.

You aserted that it is the initial infection, regardless of length or severity that is the main factor.

This from the PLoS paper I posted:

A linear trend of the frequency of suspected CCA and O. viverrini faecal egg count was observed, where an odds ratio of 14.1 was found in a group with elevated egg counts [25].

If it is the single, initial infection that was the major factor, then ALL infected would have the same risk of developing CCA. The above study says the more infected you are, the greater the chance of you having CCA.

I don't think that there is any disagreement n the medical community, that with the exception of the most severely progressed (i.e. those that already have CCA) that removal of the flukes reduces the risk of CCA.

Originally Posted by hazz

^Doesn't help with the cancer risk. It is the first infection that creates the risk for developing cancer. The length of that initial infection, its subsequent treatment and later reinfections do not add significantly to the risk of developing cancer.

Originally Posted by hazz

There are two broad paths that O. viverrini is believed to cause cancer in humans:

• It excretes a potent growth factor
  
• It provokes the immune system creating a cronic inflammatory response

There is evidence that chronic inflamitary responses can be self perpetrating [6]

My take on this evidence and the rest was that the fluke infection created an environment within the bile ducts which was conducive to cancer formation. The rapid cell division, the gene expression changes, the cronic inflammation and the physical and DNA damage that this causes. Finally, and I think most importantly, this physical damage, which will persist, enhances the cells exposure to food born nitrosal compounds further damaging the cells DNA. Maybe I am reading too much into this, but that first infection creates long term sensitivity to food born carcinogens and I recon thats the key, perhaps with genetic predispotion, to determine who and who will not develop cancer.

Thus, I assume from the above, hazz, that a chronic (ie. long lasting, continuing) inflammatory response in this case is as a result of a chronologically older, initial infestation, and that the duration of the condition, and subsequent recurring infestations have little to do with the subsequent inflammatory response leading to the development of this type of liver cancer, as opposed to chronic exposure to the flukes, ie multiple and recurring infections over a period of time.

Do the same flukes infest rice field crabs and their eggs?
Or do crab ovaries have an osmotic membrane that excludes the flukes from the ovaries and ova?
I have stayed away from eating raw fish in Thailand, but I have eaten a lot of crab eggs, packed in small rice-field crab shells I buy at Sompet market in CM.

Finally we are getting somewhere in understanding this. Even though ENT needed to be dragged along kicking and insulting most of the way.

Originally Posted by ENT

the duration of the condition, and subsequent recurring infestations have little to do with the subsequent inflammatory response leading to the development of this type of liver cancer, as opposed to chronic exposure to the flukes, ie multiple and recurring infections over a period of time.

Actually, I think Ent is saying the same thing he was before, which is wrong but the way he says it is so convoluted I'm not sure even he understands what he said.

Look, Ent, if there are flukes there then there is inflammation. If the flukes aren't there then there isn't inflammation. If there is longstanding inflammation from the flukes being there continuously on a longstanding basis, then cancer develops. Same as with cigarette smoking.


And Hazz didn't cite anything that leads one to believe otherwise.

The mark of a healthy ego is a willingness to admit one is wrong. It's no big deal to be wrong, but it says something about you if you can't admit it.

^^Dead right I'm saying the same thing, so no apology or retraction, the statement still stands.

The flukes don't have to show up later for the condition to develop.
To my understanding, they initiate the condition, then may pass out of the body and play no further part in the developing cancer.

Guyinthailand, Hazz's post gives his understanding, which is enough for me (despite his atrocious spelling). If his links do not support this, it is up to you whether you accept it or not.

ENT, the difference is that no-one has established here what the term "chronic" means. And you are vague, saying "a while back", whereas it is generally accepted in the medical world that "chronic" means at least 3 months.
The problem is that you did not clarify your position as to whether cancer would develop after a single brief exposure or a long-term initial exposure. And GIT and I asked you to clarify this, but you petulantly refused to answer; insulting instead.
Frankly, I am tiring of rotating in ever-decreasing nit-picking circles with you, in this thread and others.

There is a chance you are right that the flukes can just be there for a while, then go away, yet the inflammation remains and then cancer develops. But that is not what the citations from the scientific literature stated above in my excerpts from medscape.

But if your understanding is based on something you actually saw in the literature, then, please, by all means, share it with us.

Otherwise it's just you making things up as you go along.

Here's the science: The sooner one deworms oneself of these parasites the less chance of getting cancer.

Abbreviations: CCA, cholangiocarcinoma

"Nonetheless, heavy, long-standing infection is associated with ....cholangiocarcinoma (CCA), or cancer of the bile ducts [2,11].

"Second to tobacco use, infections are the most important preventable source of human malignancies [15–17] (Table 1). The association between the occurrence of CCA and the presence of liver flukes has been known for about 50 years [18].

CCA was observed in a high percentage of liver cancers from northeast Thailand, where the prevalence of O. viverrini infection is higher than elsewhere in this country [19]. More formal correlation studies showed that the incidence of CCA in the five major regions of Thailand varied by at least 12-fold and had a strong positive correlation with the prevalence of O. viverrini infection.... Similar correlations have been observed in populations in Laos

"Several similar surveys of Thai villagers showed a strong association between the intensity of O. viverrini infection....including suspected CCA [8,24]. A linear trend of the frequency of suspected CCA and O. viverrini faecal egg count was observed, where an odds ratio of 14.1 was found in a group with elevated egg counts [25].

PLoS Medicine: Liver Fluke Induces Cholangiocarcinoma

The initial infestation can trigger the condition, and as hazz has pointed out, I believe, recurring infections have little to do with the development of the disease once established.
So de-worming after the process kicks off is a bit like bolting the gate after the horse has gone.

You mean an initial Chronic infection, right?, an 'initial' infection that lasts a long, long time and the inflammation is long-lasting as well. Is that what you are saying?

If you mean a short initial infection that goes away after a short time yet somehow still causes cancer even though the worms were there only a short time then give a citation to that effect. The citation I just gave says in plain English it is the chronic, long-lasting infection (whether 'initial' or not) that is the problem.

If you don't have a citation saying that then you are just offering an opinion. which is fine. But it ain't science.

"Nonetheless, heavy, long-standing infection is associated with ....cholangiocarcinoma (CCA), or cancer of the bile ducts [2,11].

Oh crap ! I was copying something from my last post and edited it instead.
Oh well.....here is what I need to say:


There's just one turd you haven't cleaned up yet, ENT. You also used the words "long-lasting".


It conflicts with the following:

Originally Posted by ENT

"It is the first infection that creates the risk for developing cancer."
That is to say, a chronic (persistent, long lasting) exposure event resulting in the development of the cancer.

.

Some people will do everything in their power to not have to admit they are wrong.

Like I said, one sign of a healthy personality is being able to admit you are wrong. And when you can't do that, in the face of overwhelming evidence, then you have a problem that can best be addressed with therapy of some sort.

Okay, get ready for the next convoluted, back-tracking, hemming and hawing, circuitous blend of ifs ands and buts that will pour forth from Ent saying something like 'long lasting means initial-chronic'.

^The word "chronic" as used in this case implies long lasting, or of long duration, IMO.

The initial infection is chronologically earlier than the development of the inflamation, so you can say that a chronic event (the initial infestation) occurred, causing the condition, it's a question more of semantics, here, I think.

For instance, if after a CAT scan a fronto-parietal sulcal fosse were discovered in your brain, you'd have a "hole in the head", brain damage.
Determining how and when that occurred can be problematic, as the brain heals up around the fosse.

Nevertheless, by observing the surrounding tissue, it may be diagnosed as chronic, not because it is an ongoing development over time, rather because it is simply an old wound, demonstrated by the amount of healing that has accumulated around it.

Scars on the hand etc are the result of old injuries, they are not strictly speaking ongoing or evolving conditions(other than that they heal slowly over time) but that the injuries themselves are chronic, ie. old.

A critical condition can become acute and then chronic, and a chronic condition can become acute and then likely critical at that point.

The initial infestation ( which may leave the body) is critical to the development of the inflammation, a chain reaction, which progresses chronically until it may becomes acute, manifesting as cancer.

The initial infestation may go away, but the chain reaction it has initiated does not stop, it becomes a chronic condition.

Anyway, so much for semantics

Again, my opinion only. I haven't had time to read all of the references that hazz has given, or yours either, but I will try to at least read the abstracts and conclusions to all the cited references contained in them.

Originally Posted by ENT

^The word "chronic" as used in this case implies long lasting, or of long duration, IMO.

The initial infection is chronologically earlier than the development of the inflamation, so you can say that a chronic event (the initial infestation) occurred, causing the condition, it's a question more of semantics, here, I think.

.

Oh fuck me.