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Chapter 4: Research of molekuljarno-genetic markers in not changed mucous stumps of a stomach at the patients operated concerning a cancer in volume of a resection.

All 103 patients from research group have transferred earlier an operative measure: in volume of a subtotal distal resection of a stomach on the Billroth - I - 74 (71,9 %) patients, a subtotal distal resection of a stomach on the Billroth - II - 24 (23,3 %) and a subtotal proximal resection - 5 (4,8 %) patients.

From 103 patients who have entered into group of research, at 40 patients in the postoperative period at control esophagogastroduodenoscopy took a material which was exposed further histological and molekuljarnogeneticheskomu to researches. In all 40 biopsy samples from makroskopicheski not changed mucous stump of a stomach absence of tumoral cells and, in a number cases has been confirmed, defined an atrophic gastritis.

For the purpose of forecasting of possible development of relapse of a cancer or generalisation of tumoral process of a stomach at patients, before transferred operative treatment in volume of a resection of a stomach, the panel molekuljarnogeneticheskih markers is investigated. The used panel included research of an abnormal methylation of genes-supressorov of tumoral growth CDHl, RASSF1A, MLH1, N33, DAPK and RUNX3. It is known, that methylation/demetilirovanija disturbance is characteristic for a tumoral cell, and is defined long before a clinical manifestation of disease. Disturbance of a methylation according to the literature is one of the earliest events of a carcinogenesis and can be taped long before clinical implication of tumoral growth, in pretumor lesions, such as dysplasias and adenomas, including stomach.

The used system has been offered and aprobovana on the tumoral material received in clinic of faculty surgery of a name of N.N.Burdenko [10]. Markers from this panel authentically are more often defined in a tumour in comparison with control group, into which the biopsy material received from patients with not tumoral diseases GASTROINTESTINAL TRACT (has entered at ZHKB) [10; 40].

At panel research on a material of a tumour and morfologicheski a normal not tumoral tissue, it has been shown, that in a number cases the abnormal methylation of the offered genes is defined in the boundary tissue located within 5 sm from tumoral knot. An abnormal methylation in morfologicheski we explained to a normal boundary tissue existence fields kantserizatsii which extends and on a boundary tissue. There is an opinion, that such cells of a field can be subsequently a source of development of relapse. Researches of fields kantserizatsii are spent for a cancer of an esophagus, a bladder cancer, etc. [10]. In the given work similar researches are presented at a carcinoma of the stomach.

The fence of a material at patients was carried out during the period from 6 months to 39 months after operation. At the moment of a fence of a material for carrying out of research the tumour has already been removed, and under indications chemotherapeutic treatment is spent. For research in the postoperative period at control ezofagoga - stroduodenoskopii, as a material used not changed mucous stomach stumps. Results of our researches and full clinical characteristics of patients are resulted in table №14.

The table № 14: Clinical characteristics of patients and results of research of an abnormal methylation of genes during the postoperative period

Pain

nogo

Sweep -

liro -

van

nye

Genes

Localisation, the size and tumour invasion differen - tsirovka tumours tumour Type (on Laurenu) Soputstv

Been ill /

Having been ill

GASTROINTESTINAL TRACT

Mts

l/u

Outcome
№1 N33

CDH1

RUNX

3

Antr otd zhel - ka with pereh on 12п k-ku.
A tumour 3х4см, an invasion to mysh a layer
nizkodif - Ferentsiro - a bathroom a hell - nokarts Intestinalnyj type Hr.pankrea

tit

Mts in a liver, a pain shoj and small sal - Mors through 2г.

After operation as a result of advance for -

nik,

l/u

bolev.
№2 N33

CDH1

RUNX

3

Cancer zhel with pereh on n/gr department pishch. The tumour of 56 sm, sprouts an adventitia the Condition after PRZH nizkodif - ferentsir adenokarts Intestinalnyj type SD 2 types. GB 2ст, 3ст. HSN 2а Mts

In l/u

It is live
№3 N33

CDH1

The antral

otd.

Tumour 2х3см, invazija - all layers

nizkodif - Ferentsiro - bathing cancer Intestinalnyj type GB 2ст. SD 2типа, kompensir. Hr. atrof. A gastritis No It is live
№4 N33

CDH1

Stomach body 1,5х2,5см Invazija - all layers nizkodif - ferentsir adenokarts Intestinalnyj type DGPZH.

Polyp

sigmov.k -

ki.

Hr.atrof.g

astrit

No Generalisation (all groups

l/u)

№5 RUNX

3

The antral

otd.

Tumour 3х4см, invazija - all layers

nizkodif - ferentsir adenokarts Intestinalnyj type BA sr st tjazh.

Hr.atrof.g

astrit

Mts in a liver,

l/u

Mors in tech 2 years after operation in a consequence ge - neraliza - tsii process
№6 RUNX

3

The antral

otd.

Tumour 2х2,5см, invazija - mysh a layer

perstnevidno - A cellular cancer Diffusive type GB 2ст, 2ст. JABZH No It is live
№7 RUNX

3

The antral

otd.

Tumour 2х3см, invazija - mysh a layer

Moderately -

differen

tsirovannaja

adenokartsi

Noma

Hr.atrof.g

astrit

No It is live
№8 CDH1 The antral

otd.

Tumour 1,5х2см, inva -

Moderately -

differen

tsirovannaja

adenokartsi -

GB 3ст. An ischemic heart disease.

Hr.atrof.g

astrit

No It is live
zija - mysh a layer Noma Intestinalnyj type
№9 N33 The antral

otd.

Tumour 2х2см, invazija - mysh a layer

Moderately -

differen

tsirovannaja

adenokartsi

Noma

GB 2ст, 2ст. Hr.atrof.g astrit No It is live
№10 No The antral

otd.

Tumour 1,5х2см, invazija - mysh a layer

Moderately - differentiated adenocarcinoma Intestinalnyj type Ischemic heart disease. GB 2ст, 2ст No It is live
№11 No The antral

otd.

Tumour 2,5х2см, invazija - in sliz obol

nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type GB 2ст, 2ст No It is live
№12 No The antral

otd.

Tumour 2х3см, invazija - mysh a layer

perstnevidno - A cellular cancer Diffusive type GB 2ст, 3ст. Hr.atrof.g astrit No It is live
№13 No The antral

otd.

Tumour 1,5х2см, invazija - all layers

Moderately - differentiated adenocarcinoma Intestinalnyj type Ischemic heart disease. SD 2 types No It is live
№14 No The antral

otd.

Tumour 3х2см, invazija - mysh a layer

Moderately -

differen

tsirovannaja

adenokartsi

Noma

GB 2ст, 3ст. Hr.atrof.g astrit No It is live
№15 No Cancer a cult zhel - ka

Tumour 3х2,5см Invazija - all layers

nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type GB 3ст, 2ст. SD 2 types Mts

In l/u

It is live
Condition after SDRZH
№16 No The antral

otd.

Tumour 3х4см, invazija - mysh a layer

Moderately - differentiated adenocarcinoma Intestinalnyj type Ischemic heart disease. GB 2ст, 3 items Hr.atrof.g astrit No It is live
№17 No The antral

otd.

Tumour 4х3,5см, invazija - all layers

nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type Hr.atrof.g

astrit

Mts

In l/u

It is live
№18 No The antral

otd.

Tumour 2,5х3см, invazija - sliz obol

vysokodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type GB 2ст, 2ст. Hr.atrof.g astrit No It is live
№19 No The antral

otd.

Tumour 3х4см, invazija - mysh a layer

Moderately - differentiated adenocarcinoma Intestinalnyj type GB 2ст, 2ст. Hr.atrof.g astrit No It is live
№20 No The antral

otd.

Tumour 3,5х2см, invazija - all layers

nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type Hr.atrof.g

astrit

No It is live
№21 No Body zhel Tumour 5х6см, the invasion all layers, sprouts in a capsule podzhel glands nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type Distsirkul an encephalopathy 2ст.

Ischemic heart disease. It is broken a heart rhythm. GB 3ст. SD 2 types, dia - betich.

Mts

In l/u

Process generalisation, mors in 2 years after operation
nefropa

tija

№22 No Body zhel Tumour 4х3см, an invasion all layers It is moderated - but/nizkodif ferentsiro - a bathing adenocarcinoma JABZH No It is live
№23 No Prepyloric department zhel, tumour 1,5х2см Invazija - mucous obol nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type GB 3ст, 3ст. Ischemic heart disease JABDPK No It is live
№24 No Body zhel Tumour 2х3см Invazija - mysh a layer nizkodif - Ferentsiro - bathing Adenocarcinoma Intestinalnyj type BA, sr st gravities No It is live
№25 No Anastomosis round ulcer (a condition after SDRZH) Hr an ulcer GB 2ст, 2ст No It is live
№26 No Hr an ulcer of cardial department zhel (a condition after PRZH) Hr an ulcer GB 2ст, 1ст No It is live
№27 No The antral

otd.

Tumour 3,5х2см, invazija - all layers

nediffe - Rentsirovan - naja an adenocarcinoma Diffusive type GB 2ст, 2ст No It is live
№28 No Body zhel Tumour 3х2,5см Invazija - mysh a layer perstnevidno - A cellular cancer Diffusive type AHG 1ст No It is live
№29 No The antral

otd.

Tumour 2х2,5см, inva -

perstnevidno - A cellular cancer Diffusive GB 2ст, 2ст. Ateroskle - a mouth of penalties - dioskle - No It is live
zija - Mucous obol Type Roses. Dis - tsirkul an encephalopathy
№30 No Prepyloric department zhel, tumour 2,5х3см Invazija - mysh a layer nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type GB 2ст, 3ст No It is live
№31 No The antral

otd.

Tumour 2х3см, invazija - mysh a layer

Moderately - differentiated adenocarcinoma Intestinalnyj type VRV nizhn a game. S/p mastectomies No It is live
№32 No The antral

otd.

Tumour 3х4см, invazija - all layers

Moderately - differentiated adenocarcinoma Intestinalnyj type GB 2ст, 2ст Mts

In l/u

It is live
№33 No The antral

otd.

Tumour 2х3см, invazija - mucous obol

Moderately - differentiated adenocarcinoma Intestinalnyj type ZHKB. About - letters an atherosclerosis art nizhn konechn. No It is live
№34 No Body zhel Tumour 3,5х2,5см Invazija - all layers perstnevidno - A cellular cancer Diffusive type Diverticulum с/3 pishchev. An atherosclerosis. An emphysema of lungs. No It is live
№35 No The antral

otd.

Tumour 1,5х2см, invazija - mysh a layer

Moderately -

differen

tsirovannaja

adenokartsi

Noma

intesti -

Right kidney tumour. GB 3ст, 2ст No It is live
nalnyj type
№36 No Antral otd with transition to a cross-section colonic intestine the Tumour 4х5см, invazija - all layers growing into a wall poper an intestine rim Low-grade cancer Diffusive type Hypochromia jelly - zodefi - tsitnaja an anaemia No It is live
№37 No The antral

otd.

Tumour 3х2см, invazija - mysh a layer

Moderately - differentiated adenocarcinoma Intestinalnyj type ZHKB. An anaemia. An atherosclerosis. No It is live
№38 No The antral

otd.

Tumour 3х3см, invazija - a serous integument

perstnevidno - A cellular cancer Diffusive type Hemangioma of the right share of a liver. GB 2ст. No It is live
№39 No Antral otd with transition to a bulb 12п k Tumour 4х5см, invazija - all layers nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type Hemangioma 3 segments of a liver. HOB. Pulmonary nedostat 2ст. An emphysema of lungs. Mts

In l/u

It is live
№40 No The antral

otd

Tumour 4х3,5см, invazija - all layers

nizkodif - Ferentsiro - bathing adenocarcinoma Intestinalnyj type Ateroskle

Roses

Mts

In l/u

It is live

At all patients the morphological control of a line of a resection is carried out and

Tumoral cells it is not revealed.

Analyzing data of the above-stated table it is visible, that as a result of research two groups were generated. The patients having in mucous abnormal a methylation on one, two or three genes are carried to I group (met +) - 9 of 40 (22,5 %); patients are carried to II group (met-), in mucous which abnormal methylation has not been taped - 31 of 40 (77,5 %). At all 40 patients, at morphological research bioptatov, received of a mucous stump of a stomach, tumoral cells in preparations are not revealed.

Considering, that an abnormal methylation has been taped only at 9 from 40 () investigated patients, it is possible to tell with a larger share of probability, that surgical treatment was spent in adequate volume and according to modern principles of oncologic radicalism.

As to diseases accompanying from a gastroenteric tract, at 13 of 40 (32,5 %) patients observed a chronic atrophic gastritis. Including, at 6 from 9 (66,7 %) in group met + (r = 0,0378). At 2 of 40 (5 %) observed a peptic ulcer of a stomach and at 1 of 40 (2,5 %) a duodenum peptic ulcer. In group met + - 1 from 9 (11,1 %) the stomach peptic ulcer took place. Accordingly, it is possible to draw a conclusion, that at 7 from 9 (77,8 %) patients in group met + diseases of a gastroenteric tract in the form of a chronic atrophic gastritis and a stomach peptic ulcer took place. The aforesaid, with high probability (р2 sm 23/40 3/9 20/31 - Tumour - differentiation Highly-differents 1/40 - 1/31 - Moderately - differents 13/40 3/9 10/31 - Low-differents 16/40 5/9 11/31 - Low/moderately diff 1/40 - 1/31 Crico-kletochn. 6/40 1/9 5/31 - nedifferentsirov. A cancer 1/40 - 1/31 - Resection edges Tumoral cells not vyjavl 40/40 9/9 31/31 Innidiation in regionarnye l/u Purely 31/40 25/31 Mts 9/40 3/9 6/31 - Kept away mts 2/9 0/31 0,0462 Outcome Are live 37/40 30/31 Process generalisation 4/40 3/9 1/31 0,029 Mors 3/40 2/9 1/31 Accompanying diseases of a stomach and 12п. Intestines Chronic atrophic gastritis 13/40 6/9 7/31 0,0378 Stomach peptic ulcer 2/40 1/9 1/31 - Peptic ulcer 12п intestines 1/40 - 1/31 - Accompanying zabo - levaenija GASTROINTESTINAL TRACT 13/40 7/9 6/31 0,0077

We did not manage to tap authentic associations between clinical characteristics of remote tumours, such as tumoral localisation, the size, presence of invasive growth, cleanliness of a line of a resection and presence of metastasises in l/u with a hypermethylation in a stomach cult.

All patients were observed in unit within at least 3 years after the performed operation. As a result from group of the patients having an abnormal methylation at least of one gene, two patients have died of disease generalisation in 2 years, and one patient has generalisation, but is still live, as has not passed yet two-year-old term of observation. As a result disease generalisation in this group is defined at 3 of 9 (33,3 %) patients.

In group of the patients who do not have an abnormal methylation of investigated genes, generalisation of process and mors within 2 years after operation is defined at one patient 1 of 31 (3,2 %). Thus, the negative outcome of disease authentically more often (р=0,0299) arises in group (met +), than in group (met-), that allows to survey presence of a methylation of our system of genes as a marker of the bad forecast, to be exact - generalisations of tumoral process.

In other important clinical parametre defining tactics of conducting of the concrete patient, even after an oncotomy, presence of metahundred - zirovanija tumours is. From the table it is visible, that in I group (met +) the metastatic lesion of lymphonoduses was defined at 3 of 9 (33,3 %) patients, in II group (met-) - at 6 of 31 (19,4 %) patients. At comparison of these groups of an authentic difference it is not received, that allows to exclude communication between hypermethylation presence in a cult of a stomach and an innidiation in lymphonoduses. However, at comparison of groups of patients with presence or absence of the remote metastasises, we managed to tap, that in group with remote metastasises abnormal methylation is defined authentically more often (р=0,0462). It is obvious, that in group of the patients who do not have remote metastasises, the methylation was not defined.

At the characteristic of system of molekuljarno-genetic markers the special attention was given to selection of the genes making system. All these genes are tumoral supressorami and are of great importance for a stomach carcinogenesis. From six investigated genes, the abnormal methylation in bioptatah mucous a stomach has been defined only at three genes (N33, CDHl, RUNX3). Methylations of genes RASSFlА, MLHl and DAPK it has not been taped in one of 40 cases. It is possible to explain absence of change of these genes to that their abnormal methylation occurs in already growing tumour and defines clinical lines of tumoral growth, but is not early event in a stomach carcinogenesis. From 9 persons making group met +, the methylation on three genes N33, CDHl, RUNX3 was observed at 2 of 40 patients (5 %), on two genes N33, CDHl - at 2 of 40 sick (5 %), on one: RUNX3 - at 3 from 40 patients (7,5 %), on N33 - at 1 (2,5 %) and on CDHl - too at 1 (2,5 %).

Hypermethylation RUNX3, CDHl N33 is shown in precancerous damages, such as an intestinal metaplasia and a stomach adenoma that specifies that their inactivation is one of early events in a carcinogenesis of a stomach [125].

Presence of a hypermethylation of genes in morfologicheski to a normal stump of a stomach can occur for various reasons. It can be bound as to development of tumoral process (formation of possible relapse or disease generalisation), and to be reflexion of its molekuljarno-genetic characteristics, and to be property of a macroorganism in which the tumour develops, and to be bound with the years, a diet or other characteristics.

Among patients of group met + with a residual methylation, the age 7 of 9 made from 55-65, and only at two was from 70 till 80 years. The group met - included patients of the same age 22 of 31 50-70 years, and 9 from 31 had age criteria 70 and is more senior. Such distribution on age has allowed us to exclude a methylation, assotsiirovannoe with the years.

However, there is opened a question with the patient №21 of group (met-) at which generalisation process has arisen without a methylation of investigated genes in a cult (a clinical example №4 in chapter 3). In this case, most likely it is possible to speak about presence of micrometastasises in regionarnye lymphonoduses, as was a source of generalisation of process in 2 years after the executed operation. And considering age of the patient 84 years and that at elderly patients processes of a metabolism and as consequence - development of generalisation of process or disease relapses proceed much more slowly, than at young - these can explain process generalisation in 2 years, instead of earlier.

Tumour presence in the anamnesis, and interrelation epigeneticheskih changes and tumoral growth allows to assume, that the abnormal methylation of genes in a stomach cult can be bound to field presence kantserizatsii and continuation of tumoral process in a stomach. Therefore the further observation over the remained six patients from group met + as the probability of generalisation of tumoral process at them is high enough is necessary. In connection with the aforesaid, patients should pass a minimum of times in a year the complex inspection including analyses of blood, the general, biochemical and definition onkomarkerov, specific to a carcinoma of the stomach - SA 72-4, SA 19-9 and REA, ultrasonic. It is necessary to include in this inspection MSKT organs of an abdominal cavity, MSKT a thorax for an exception of the remote lesions, ezofagogastroduodeno - skopiju for diagnostics of possible development of local relapse or presence of precancerous diseases, such as a gastritis of a stump of a stomach, an anastomositis or anastomosis round ulcers;

Summarising all aforesaid, it is possible to say that use of molekuljarno-genetic markers at the patients who have transferred various kinds of a resection of a stomach concerning a cancer, is of great importance and allows to prognosticate with a high share of probability possible development of generalisation of tumoral process, that, undoubtedly, introduction of routine application of the given panel in clinical practice demands.

The conclusion.

Despite the tendency of last years to depression of a case rate by a carcinoma of the stomach, the given pathology occupies one of leading places in case rate and mortality structure [3; 80].

Now the surgical method is recognised not only a leading component, but also the "gold" standard of radical treatment of a carcinoma of the stomach [21]. The subtotal distal resection of a stomach with extensive limfadenektomiej is for today one of the most widespread operative measures [80]. An estimation of result of treatment and the disease forecast influence volume dissektsii and an establishment of a stage of disease [71].

We analyse the remote results of operative treatment of 103 patients during the period from December, 2009 till December, 2012 were on treatment in clinic of faculty surgery of a name of N.N.Burdenko. All patients have been operated concerning a carcinoma of the stomach in volume of subtotal distal or proximal resections with dilated limfadenektomiej. As indications to performance of a subtotal distal resection of a stomach considered tumours of antral department and the bottom third of body of a stomach, at absence in its proximal department of precancerous changes of a mucosa, such as polyps, a serious dysplasia [69]. A subtotal proximal resection of a stomach carried out the patient with small jukstakardialnym a cancer [74].

In research patients prevailed is more senior 60 years - 77 of 103 sick (74,8 %), mainly the man - 54 of 103 (52,4 %). Accompanying, and as a matter of fact rival diseases from the party warmly - vascular and respiratory systems were at 68 % (70 of 103) patients.

We had been used the international classification by system TNM (7th edition, UICC 2009г) on which grouped patients in stages. Patients have been included in work with I and II stages of disease - 73 of 103 (70,9 %) mainly. The given sample explained that one of research problems was the estimation of efficiency of the remote results of surgical treatment sick of a carcinoma of the stomach, competency of performance of resections with dilated limfadenektomiej concerning a cancer and possibility of development of relapse of disease or generalisation of tumoral process after such volume of an operative measure at patients with early forms of disease, and also their availability to carrying out molekuljarno - genetic researches.

On histological structure the adenocarcinoma - 90,3 % of all tumours, basically low degree of a differentiation - 53 of 103 (51,5 %) patients prevailed.

After preoperative preparation all patients have been operated. The number of subtotal distal resections of a stomach with dilated limfadenektomiej has made 95,2 %, that is 98 of 103 patients, 5 (4,8 %) the patient carried out proximal resections of a stomach.

During a reconstructive stage of operation after subtotal distal resections of a stomach we carried out reconstruction with applying of hectares - stroduodenoanastomoza on type the extremity in the extremity more often. The given preference explains our experience and studying of the literature which show, that the subtotal distal resection of a stomach on the first way of the Billroth at a cancer provides both necessary volume of a resection of an organ, and the good immediate and remote results [71; 73]. Are In such a way operated 74 of 103 patients that makes 71,9 % of all patients. As indications for reconstruction performance on the second way of the Billroth considered tumour diffusion on a duodenum and necessity of a resection of its top-horizontal part, and also presence of conglomerates of metastatic knots in the field of the gatekeeper. The given kind of an operative measure have transferred 24 (23,3 %) the patient.

The combined interventions are executed 9 of 103 (8,7 %) patients. 4 (3,9 %) - an extensive resection mezokolon, 2 (1,9 %) - a plane resection of a head of a pancreas, 3 (2,9 %) - an atypical resection of a liver.

In the postoperative period of complication observed at 21 of 103 (20,4 %) patients. Most often taped complications from breath organs - the pleuritis has arisen at 5 of 103 (4,9 %) patients and also at 5 from 103 patients the pyesis of postoperative wounds has been diagnosed. Equally, on 4 of 103 (3,9 %) patients, observed the phenomena of a postoperative hydropic pancreatitis and a pneumonia. At 2 (1,9 %) patients acute warmly - vascular insufficiency has developed. And only the incompetence of hectares - is diagnosed for one patient (1 %) stroduodenoanastomoza, that the exception of a passage of a chyme through an anastomosis, the equipment nazointestinalnogo a probe for ligament Trejtsa and application of fibrinous glue in defect area has successfully begun to live on spent conservative therapy which included decompression of area of an anastomosis. Intraoperatsionnyh complications and lethal outcomes were not.

Subtotal proximal resection of a stomach carried out 5 of 103 (4,9 %) patients at whom was small jukstakardialnyj a cancer, mainly to I stage. Only at 1 of 5 (20,0 %) patients in the postoperative period within five days remained the phenomena gastrostaza, that has been successfully stopped by spent conservative therapy. Lethal outcomes after the given kind of an operative measure it has not been noted [74].

Subtotal distal resections of a stomach mainly carried out the patient with I and II stages of disease, more often without the remote lesions, that obviously could cause the good remote results of treatment and as consequence - high survival rate. In case of proximal resections of a stomach it was a question about small jukstakardialnyh cancers, in basic I stage and without the remote metastasises. But even the analysis of the remote survival rate of small group of patients specifies in efficiency and radicalism of the spent treatment that proves competency of performance of resections of a stomach at a cancer under condition of operation performance in volume R0 and dilated limfadenektomii.

Characterising on degree of radicalism of the executed surgical interventions - in volume R0 85,4 % of operations (88 of 103 patients) are executed; R1 - 10,7 % (11 patients) - at histological research are taped tumoral cells in resection edges; R2 - 3,9 % (4 patients) - took place nerezektabelnaja a periaortal lymphadenopathy and the left metastasises in a liver.

Thus, from 103 sick tumoral cells in proximal edge of a resection are taped at 11 (10,7 %). From them 9 patients are executed obviously cytoreductive operations as took place bilobarnoe a metastatic lesion of a liver and extensive metastatic periaortal conglomerates of lymphonoduses. In one case to the patient the operative measure volume has been reduced from - for presence of a serious rival disease and 1 patient could transfer a gastrectomy, but to formal signs was possible to execute a subtotal distal resection, as has been made. These two patients had a disease relapse, and they have been repeatedly operated in volume an extirpation of a stump of a stomach with a resection abdominal and nizhnegrudnogo department of an esophagus with applying ezofagoejunoanastomoza. Now both are live also data for relapse of disease and generalisation of process are not present.

In the postoperative period chemotherapeutic treatment spent 76 (74 %) from 103 patients. 27 (26 %) to patients did not carry out chemotherapy, as it was a question of patients with a cancer in situ, ІА a stage, patients with a decompensation of serious rival diseases or patients independently refused the further carrying out of chemotherapy. At 3 of 76 sick (3,9 %) should be changed the primary scheme of chemotherapy as it has appeared it is noneffective, that was clinically shown by disease advance.

Analyzing the remote results of the surgical treatment spent by us sick by a carcinoma of the stomach it is taped, that the indicator of 2 summer survival rates after a subtotal distal resection of a stomach has made 980,06 %, 3летней - 970,09 %; after proximal resections of a stomach - 100 %, that in correlation with gravity of rival diseases and age of the operated patients in comparison with data world the statistican (table №13 in chapter 3) allows to speak about legitimacy of chosen medical tactics from the point of view of oncologic radicalism.

We have estimated efficiency of complex treatment of patients that included an operative measure and postoperative system chemotherapy in the presence of indications to it. It has allowed us to say once again that performance of resections of a stomach at a cancer in volume R0 in a combination with dilated limfadenektomiej and if necessary carrying out of chemotherapeutic treatment is competent tactics of conducting sick of a carcinoma of the stomach and does not reduce volume of oncologic radicalism. If it is a question of performance of obviously cytoreductive operations or depression of volume of operative treatment because of presence of a serious rival disease the given tactics allows to prolong a life of patients at least for 2-3 years, thus not reducing its quality.

However, even performance of operative measures in volume R0 does not give an unequivocal guarantee of prevention of development of relapse of disease or generalisation of tumoral process that brings an attention to the question on working out and application of additional methods of diagnostics. For today the molekuljarno-genetic markers based on use of DNA and RNK of technologies [22] start to get the increasing value.

For the purpose of forecasting of possible development of relapse of a carcinoma of the stomach or generalisation of tumoral process at patients, before operated in volume of a resection of a stomach, in our work we estimated molekuljarno-genetic changes in postoperative bioptatah morfologicheski not changed mucous stump of the stomach, received at esophagogastroduodenoscopy. Research of an abnormal methylation of genes-supressorov of tumoral growth CDH1, RASSF1A, MLH1, N33, DAPK and RUNX3 has been carried out. It is known, that epigeneticheskie DNA changes which methylation disturbance reguljatornyh districts of genes concerns, are the earliest events in the course of a carcinogenesis, leading to damage of an expression of the genes responsible for regulation of a cellular cycle, a proliferation and a differentiation. These changes frame certain potential of molekuljarno-genetic instability which during time can be realised in the form of tumoral growth. Now the abnormal methylation is a tumoral marker which appears to a clinical manifestation of disease [139].

The used system of molekuljarno-genetic markers has been offered and tested on the tumoral material received in clinic of faculty surgery of a name of N.N.Burdenko [10]. Markers of this panel authentically are more often defined in a tumour, in comparison with control group of the patients having not tumoral diseases GASTROINTESTINAL TRACT (at ZHKB) [10; 40].

From 103 patients who have entered into research, before operated concerning a cancer in volume of a resection of a stomach molekuljarno-genetic markers investigated at 40 patients in a biopsy material of not changed mucous stump of the stomach, received at control esophagogastroduodenoscopy. Morphological research of these samples has confirmed absence in them of tumoral cells, and at a part of patients the atrophic gastritis has been taped. In each of 40 samples investigated an abnormal methylation of genes CDHl, RASSF1A, MLH1, N33, DAPK and RUNX3.

The genes chosen for the analysis of a methylation, possess properties tumoral supressorov, immediately influence restraint of tumoral growth. Their inactivation by means of an abnormal methylation is characteristic for various kinds of tumours, is not taped at development of inflammatory diseases of various organs, and also at reversible hyperplastic processes [86].

The abnormal methylation on one, two or three genes is taped at 9 of 40 sick (22,5 %) which have made group (met +). At 31 of 40 (77,5 %) patients the methylation was absent - group (met-). In the spent research from six genes the abnormal methylation was defined at N33, CDH1 and RUNX3, the methylation of genes RASSF1A, MLH1 and DAPK in morfologicheski not changed mucous stump of a stomach was not defined. Considering, that the abnormal methylation of genes is taped only at 9/40 patients that makes 22,5 % of patients for which the molekuljarno-genetic analysis is carried out, allows to speak with a larger share of probability about adequacy of the executed surgical treatment with the account not only cleanliness of a line of a resection and adequate limfadenektomii, but also the molekuljarno-genetic characteristic of a mucous stump of a stomach. The received result allows to confirm competency of performance of operative measures in volume of subtotal distal or proximal resections of a stomach at a cancer in a combination with dilated limfadenektomiej.

For the purpose of revealing of prognostic clinical markers, we investigated hypermethylation communication in not changed mucous stumps of a stomach with clinical characteristics before a remote tumour, such as tumour localisation, its size, presence of invasive growth, differentiation degree, and also cleanliness of a line of a resection and presence of metastasises in regionarnye limfoticheskie knots and other organs (liver). The material fence was carried out during the period from 6 months till 39 months after operation.

During research we did not manage to tap communication it is abnormal methylations in not changed mucous stumps of a stomach with such clinical characteristics of a primary tumour, as localisation, the size of a tumour, presence of invasive growth, a differentiation, cleanliness of a line of a resection, an innidiation in limfoticheskie knots.

We show, that absence of communication between a methylation and lokoregionarnym a tumour innidiation, but in the presence of the remote metastasises in a liver, a methylation is defined authentically more often (р=0,0462), on the contrary, in group of the patients who do not have remote metastasises, the abnormal methylation has not been taped.

At 78 % of patients in group with the taped abnormal methylation diseases of a gastroenteric tract, such as a chronic atrophic gastritis and a stomach peptic ulcer took place. The received result with high probability (r

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A source: Chekunova Natalia Valerevna. MOLECULAR-GENETIC DIAGNOSTICS OF CHANGE OF MUSCULAR CULT OF THE STOMACH IN PATIENTS OPERATED FOR CANCER. Thesis for the degree of candidate of medical sciences. MOSCOW - 2014. 2014

More on topic Chapter 4: Research of molekuljarno-genetic markers in not changed mucous stumps of a stomach at the patients operated concerning a cancer in volume of a resection.:

  1. Chekunova Natalia Valerevna. MOLEKULJARNO-GENETIC DIAGNOSTICS CHANGE of the MUCOUS STUMP of the STOMACH At the PATIENTS OPERATED CONCERNING the CANCER. The dissertation on competition of a scientific degree of the candidate of medical sciences. Moscow -,
  2. CHAPTER 1. A stomach resection in surgical treatment of a cancer and a role of molekuljarno-genetic research in the forecast of development of relapse of a carcinoma of the stomach.
  3. Molekuljarno-genetic markers.
  4. the Analysis of survival rate of the patients who have transferred various kinds of a resection of a stomach concerning a cancer.
  5. the Molekuljarno-genetic markers studied in work
  6. CHAPTER 1. The CARCINOMA OF THE STOMACH - the MODERN CONDITION of the PROBLEM And the ROLE of MOLEKULJARNO-GENETIC FACTORS In IMPROVEMENT of RESULTS of TREATMENT of the CARCINOMA OF THE STOMACH
  7. Molekuljarno genetic aspects of a carcinogenesis at a carcinoma of the stomach
  8. a subtotal distal resection of a stomach at a cancer.
  9. a subtotal proximal resection of a stomach at a cancer.
  10. the Remote results of treatment sick mestnorasprostranennym a carcinoma of the stomach with the account molekuljarno-genetic features of a tumour
  11. Molekuljarno-genetic research
  12. 1.2. Influence of volume of a resection on the general life expectancy of patients with malignant gliomami a brain
  13. molekuljarno-genetic methods of research