Potential of NLS method in diagnosing gastric and colonic cancers.
Topical problems of NLS-diagnostic
(Theoretical and clinical)
Potential of NLS method in diagnosing gastric and colonic cancers.
P.A.Svetlova, N.A Sorokina, T.G. Kuznetsova, V.I. Nesterova, L.A.Yankina, N.V. Tatisova
The non-linear diagnostics method (NLS) use in the Oberon device has been actively practiced lately as many medical institutions. The most tangible results were achieved by using the NLS method as a means of dispensary observation. In the course of its development and advancement the method the method has become a foremost tool of diagnostic and observation with respect of widespread digestive organs diseases : it allows to promptly collect detailed information about the lesion and its pattern and asses the treatment efficiency. That kind disease include gastrodoudenal ulcer, chronic gastritis, and also benign and malignant gastric and colonic tumors. The specific character and working conditions of the therapeutic an dl=clinical institutions in Russia allow extensively employ the NLS method not only for diagnosing disease with some symptoms but also for dispensary observation and what is more, practically all the patients in need of examination can be placed under observation. So physician now can cover patients with the changes that are latent and can only be verified by means of NLS. Specifically, such patients include those having precancerous disease or mucous disturbances in the upper and/or lower sections latent in a certain phase.
According to the data acquired by some medical specialists, using the devices for NLS-diagnostics, and based on annual research in thousands of cases, the frequency of detecting focal or diffuses changes, typical for chronic atrophic gastritis in patient over 50 years old, is within 30-40%.the analysis of the spectral examination of pattern-different section of focal changes in stomach mucosa shows that different symptoms of diseases including intestinal metaplasia and epithelia dysplasia can be detected in them just as often. During the NLS analysis symptom of gastric ulces where recorded in about 5% of cases, polyps in stomach in 7%, and polyps in colons in 45% of cases. Thus, even NLS analysis result alone, without other risk factors taken into account, include the most of the patients in the respective age group appear to be among those who need dynamic observation because of potential gastric cancer (GC) or colonic cancer (CC).
According to the cancer register for 1999-2000, the values of gastric an colons cancer cases were 80.9 and 53.1 respectively per 100000 patients and the death according to the mortality statistics was 47.35 and 19.5%. According to conclusion of the therapy-diagnosis unit, with about 70% patients under active dispensary observation, the pathologies of this kind are likely to be detected as often as in 0.4-0.8% of cases. Therefore, the NLS screening would allow to detect GC or CC in about every 15th-20th examinee.
Considering that emergence of clinical sings is one of the incentives for a patient to take medical advices and a reason for hardware-based examination, some clinical implication and their pattern were evaluated in the case of the above mentioned diseases. As fallow in the results,720 patient affected by CG or CC the condition appeared to be symptoms free in 42% and 32% of cases respectively or there were some sings characteristic of previous chronic digestive track diseases that was a case in 77% and 92% for the 1 phase, 56% and 68% for the 2nd phase, 23% and 32% for the 3rd phase, and 8% for the 4th phase of this diseases. The clinical implication at a gastric cancer were of a point-dyspepsia syndrome nature typical for the lesion in the upper section in digestive track. At a colonic cancer subgroups were segregated with dominating sings of intestinal hemorrhage, disturbed evacuation or abdominal pain. A certain interrelationship was proven between the pattern of the clinical implications lasted less than 3 months in 26% of patients the CC developed actually within a few days. It should be noted that so-called "minor sing syndrome" correspond to some later phases of the disease. The same was true fro lab examination data where the change became evident during phases III and IV (2).
healthy tissue - MISSING IMAGE!!!!!!!
The result for NLS daignostics for the initial phases of gastric cancer in a series of 104 examination showed that in 72@ of cases the physicians on the assumption of the spectral similarity to the reference standard, regarded the lesion as benign and indicative of focal mucosa hyperplasia, polyp, and area of local information, wall deformation or small ulcer. The probability for detection sings of malignant changes found out in the elimination mode was under 1%. Of 134 cases of colonic cancer in phase 1 malignant adenomas were detected in 58% of patients. The rest of the patients were found to have the so-called "minor" changes of cancer, like polyps, atrophic gastritis or atrophic-hyper plastic gastritis. The endoscopic verification of GC and CC with reference to the diacrisis of phases II,III and IV of the discases completely confirmed the results of the NLS-investigation.
172 patients were found to have to have GC or CC discovered by NLS examination conducted within a less than a year interval. among them 62% of patients. Among 62% of patients had an initial phase of gastric cancer and 38% of the patients during previous observation were found to have some or other sings of chronic gastritis in the form of focal mucos hyperplasia, local inflamination or wall deformation. According to morphological investigation, the said sections were of a benign nature and cancer development therein over the last year only. In the rest of the patients the macroscopic changes corresponding to malignant affection (spectrial similarity to "gastric carcinoma" reference standard D<0.425) occurred in the span between the last examination. This preceding endoscopy detected atrophic gastritis free focal changes in the area of the development tumor. Similar NLS data were acquired for 38 patients who during a year's observation were diagnosed to have developed a tumor corresponding to phases II and III.
The NLS of the colon and straight intestine was performed a year before tumors were diagnosed in 21 patients affected by malignant polyps, of whom 17 had been under active observation because of polyposis, while no formation of that kind was in evidence during the initial examination. In addition, within the same time span 13 patients were examined who were diagnosed with precancerous condition (spectral similarity to straight intestine carcinoma, reference standard D>0.7) an minor form of cancer. In 6 of the patients the tumor developed in area of endoscopic polypectomy after they had a large villous adenoma removed. Thus, in 34 (27%) of 121 patients, who were diagnosed to have a malignant polyp conditions in phase I or a small size tumor, colonic cancer developed within a year.
36 patients examined within the same time interval were found to have the condition in phase II and II just as frequently. 28 of them were subjected to medical regular check -ups with no clinical sings of the disease of evidence in any of them. 8 patients, within 3-7 months prior to tumor diagnosis, began to shows sings of growly anemia or progression stool retention. This dispensary observation data for these patients, with the NLS method employed a year before the cancer was developed, had indicated the tumor.
There are two indicated factors known to be paramount importance for malignant disease diagnosis hey are the quality of clinical and diagnostic techniques and the specific pattern of the disease progress which actually determine the dynamic of the disease progression. Considering capabilities and working condition in the therapeutic institutions, the presented data on gastric and colonic diagnoses may to certain extent be regarded as optimum. It implies, that even if all the patients were readily diagnose with the disease during the dispensary observation (actually it is a matter of 60%), the phase I condition could been detected only in 40% of them. The analysis of causes of the late diagnosis cases suggests that such cases could prevented by improving organizational and methodical work.
Furthermore, the focus should be placed on the specific features of the diseases progress which are of great, and possibly of vital importance for tumor detection. The analysis of the available data allows to assume that tumor may develop within the short time interval reaching the size of either "minor cancer" or extensive lesion. All that confirms the idea that the tumor growth dynamics in different patients and in the different phases of the diseases id likely to very and be both continuous and discrete pattern. So a possible scenario of tumor development could be the emergence of "early" gastric cancer against the background of precancerous gastric diseases with the subsequent prolonged period of existence in the initial phase of the condition in advance. The colonic cancer development through the benign phase and then through a malignant adenoma is not the only possible scenery it can processed. Tumor can develop de novo and here too. a variant of comparatively slow or fast growth in potential. This provides an explanation for an "accidental" detection of patients with fairly large tumors during dispensary observation and a great number of patients with short clinical anamnesis and late phases of the diseases.
Thus, NLS can be considered as an adequate method for diagnosis gastric and colonic cancers. The difficulties in dealing with NLS interpretation largely concern the initial phases were the frequency of diseases detection depends in the long run on any focal changes in the mucosa in the case of chronic gastritis and on keeping the patient under dynamic observation on the given modes of elimination and NLS analysis involved. The submitted results allow to segregate two principal variants of the diseases diagnosis. The first one suggest "accidental" tumor detection during NLS-investigation; neither clinical nor other familiar sings of disease are in evidence or their intensity ia an insufficient reason for the patient to see the doctor. The second variant occurs the patient develop clinical implications which impel physician to carry out the respective investigation for them. The result of diacrisis of gastric or colonic cancers indicate that for most patient the problem of early diagnosis can not be solved, not only because of certain organization factors but also and primarily because of the specific pattern of the disease process and its manifestation. However, the actual opportunities for improving the well-timed diseases diagnosis in practical public health conditions lie, primarily, in increasing the number of patients to be examined by means of the NLS-method within the framework of health survey and also in a timely and complete examination of the patients who are suspected to have the disease.
New potentials of NLS-method in colonic neoplasm diagnostic.
V.I.Nesterova, T.G.Kuznetsova, V.I.Metlushko, N.L.Ogluzdina
Colonoscopy is successfully used to diagnose colon new growths. Based on the number of indications endoscopy investigation allows to get reliable information about the colonic growth surface in order to correctly classify its pattern and take a sample for morphologiacal identification. Yet, colonoscopy does not give an idea of the kind of internal structure the new growth has, nor does it allow to assess the depth of the invasion of the colon wall by a malignant tumor, determine its proliferation to adjacent organs or metastases to regional lymph nodes. Beside, colonoscopy does not provide information about extra intestinal new growths unless they have already permeated the intestinal wall.
The NLS-investigation of the colon using 4.9 GHz high frequency nonlinear sensor can help clear up all of these issues.
The NLS-investigation allows to examine intestinal wall layers and the adrectal cellular tissue.
The research aimed to define the potential of the NLS-method in a more specific diagnostics of straight-and segmented intestine tumor.
The matter and investigation methods
In order to achieve the set goal 87 patients were examined by in whom 91 new growths were investigated by means of the NLS-method. The examinees included 41 men and 46 women age from 31 to 83 with most of them (82%)aged from 50 and over. All the patient affected by colon new growths were given one or another kind of surgical treatment depending on the pattern, size and localization of the growth. Among them in 23 cases endoscopic polypectomy was performed, in 61 cases a resection was done on different parts of the colon and in 3 patients transanal endomicrosurgery was performed. All of the NLS-investigation results were verified by a pathomorphological examination of macro preparation according to which the colonic ne growths were represented by simple tumors in 30 cases and by glandular cancers with different degrees of differentiation in 61 cases.
The stage of the malignant process were defined according to TNM classification adapted by International Anticancer Association in 1997 (the 5th revision) Phase T1 was diagnosed in 13 patients (21%), phase T2 -in 26 patients (43%), phase T3 in 17 patients (28%) and phase T4 in5 patients (8%).
According to a pathomorphological examination, metastases into regional lymph nodes were detected in 11 of 61 cases.
All the patient underwent NLS-investigation and ultrasound colonoscopy to diagnose and localize new growths, define their size, growth patterns and approximate morphological characteristics, and also ultrasound scanning of the abdominal cavity and small pelvis organs to assess the condition of the organs adjacent to the colon and diagnose distant metastases.
The NLS-investigation used the Oberon-4011 device equipped with a 4.9 GHz nonlinear sensor manufactured by the Institute of Practical Psychophysics (Russia) and Clinic Tech Inc. (USA). The endoscopic ultrasonography made use of the endoscopic ultrasonographic system UM-20 complete with the ultrasonie colonoscope CF-UM20 (Olympus, Japan). The echographia of the abdominal cavity made use of the diagnostic unit SSD-630 (Aloka, Japan) and Logiq-700 (General Electric, USA)
Discussion of results
We know from experience that every NLS-investigation should be preceded by diagnostic colonoscopy, which evaluates anatomic characteristic of the colon and defines the number, localization and macroscople characteristic of the new growths, and by ultrasound scanning of the abdominal cavity aw well. A through transabdominal ultrasound scanning is required to assess the condition of the organs adjacent to the colon and diagnose remote metastasizes.
A comparison of the NLS results with those of pathomorphological investigation was made in order to define the potentials of the NLS-method in differential diagnostics of benign and malignant colonic new growths.
The result of the NLS-investigation coincided with the apthomorphological investigation in 87 of 91 cases. Most of the errors occurred in diagnosing colon adenomas. In 6 of 31 cases the patient was suspected of having cancer. The analysis of the observation noted that the difficulties in diagnostics were related to the deformation of intestinal wall layers due to the pressure of a nodal villous tumor rather than to a genuine invasion. To false-negative results were obtained in the case of malignant adenoma and cancer decreases,
Thus the accuracy of the NLS method in differential diagnostics of malignant and benign colon tumors amounted to 81.33% and sensitivity to 79.8%, while the specificity made 76.4%.
The method of treatment to be chosen for patients affected by colon cancer depends on the tumor process phase. A comparison was made to he pathomorphological investigation data in 61 cases in order to assess the diagnostic efficiency of the NLS-method in classifying the colonic cancer phase.
The correct definition of the phase of tumor process was possible in 68.4% of the observations. The best results were obtained in defining phases T3 and T4, where the diagnostic accuracy was 78.2% and 81.2% respectively. It should be noted that most of the errors occurred in determining phases T1 and T2, were the data of NLS and pathomorphological investigations coincided only in 54.2% and 47.4% of the observations respectively.
In diagnosing phase T1 mistakes were made in 4 cases with 3 of the errors toward overstating the phase; in once case sings of intestinal wall invasion were not found and the tumor was taken for adenoma. In the analysis of phase T2 diagnostic errors in overstated phases were noted in 7 of 9 cases; an understatement of phase of the tumor process occurred in one case and yet in one case no evidence of invasion proved to be fond. The analysis of the post surgical morphological conclusions made it clear that in 6 of 7 false positive result pathomorphological investigation of macro preparation detected a deeper infiltration into the intestinal wall. However according to microscopy examination, the filtration was on inflammatory rather than of a tumorous kind. It should also be noted that in all of the cases it had to do with an infiltrative tumorous process in the inferior ampullar section of the straight intestine free of serous membrane while the inflammatory infiltration area was located in adrectal cellular tissue.
To find out the causes the present difficulties for diagnosis the efficiency of the NLS method was analyzed in function of the size, localization and form of germination of neoplasms. The best results were obtained in diagnosing new growths size under 2 cm and over 5 cm.
The epithelia tumor over 5 cm in sizes is represented by phases T3 and T4 in 12 of 17 cases. It has to be noted, that the large neoplasms the data of NLS essay did not coincide with pathomorphological data only in phase T2 where the process phase was overestimate because of the presence of the inflammatory infiltration in deeper layers, than the layers where the tumoral invasion occurred. Thus, at neoplasms larger than 5 cm in size the diagnostic of the invasion degree of the intestinal wall is feasible in 78,2% of observation. High result was also obtained at the estimation of depth of tumoral invasion by neoplasms sized up to 2 cm. most of them are represented by a tumor in phases T1 and T2. The results of ultrasonic colonoscopy have coincided with those pathomorphologic conclusions in 76.7% of the observation. It should also be noted, the tumours up to 2 cm are most convenient for examination since they have the least number of artefacts.
At this essay the greatest groups were the tumours sized from 2 to 5 cm, where the result proved to be lower, than in two first groups. The NLS data and those of the pathomorphological essays coincided in 66.7% of cases. An appreciable share of mistake (60%) occurred in phase T2, where the intestinal wall invasion depth was overestimated in all observation.
The great value has the fact, according to the pathomorphologic essay, in 5 of 6 cases of hyperdiagnostics apart fro the tumoral infiltration an expressed inflammation was detected in deeper layers of the intestinal wall. The relatively low accuracy of diagnosed depth of the intestinal wall invasion by tumor sized from 2 to 5 cm is due to the fact that 24 of 30 observations of this group corresponded to phases T2 and T3. The differential diagnostics of the tumoral infiltration depth in this phases is complex.
At the next research stage we made comparative analysis of the effect of the form of growth of the neoplasm for accuracy of defining the phase of the tunoral invasion in the intestinal wall. All neoplasms were classified into three groups, in function of the shape otf the tumor growth: polipiform, saucer shaped and infiltrative.
The highest results were obtained when diagnostic the phases of the caucer-shaped growth cancer process where the accuracy of the defining the tumoral invasion in the intestinal wall was 78.3%.
It seems however impossible to fully estimate the accuracy ot the NLS method in defining the depth of a tumoral invasion at neoplasms with saucershaped growth because of its dismall occurrence among other forms n patients surveyed by us.
The polipiform of the growth was noted in 30 neoplasms. The growths had a distinct interface with unaltered sections of the intestinal wall and did not block the intestine lumen by more than half, which created favorable condition conditions for the survey. The accuracy of NLS method in defining the depth of tumoral invasion in the intestine wall was as high as 65%. It has to be noted, that half if all cases divergent with the pathomorphologic conclusions is due to the overestimate depth of tumoral infiltration at defining the phase T2, which is connected with the presence of perifocal inflammation.
This fact suggest difficulties in defining the phase of cancer process in cases where the tumoral invasion is compounded by the inflammatory component penetrating deeper layers of the intestinal wall and beyond its limits.
The neoplasms with in infiltrative growth shape have proved to be most difficulty in defining the degree of the tumoral invasion in to the intestinal wall. tn this group the result of NLS-method and those of the pathomorphologic essays coincided only in 49.8% of observations. It was due to the fact that these neoplasms, as a rule, had a large size and occupied more than a half of the intestine wall circle.
In the next investigation phase was estimated the accuracy of the NLS method in defining the degree of the intestinal wall invasion depending on the tumor location in the colon.
In 40 cases the tumor was localized in the rectum and in 21 cases in the segmented intestine. The accuracy of diagnosing the phase of the tumoral process in the colonic intestine is significantly height that at finding the tumoral invasion depth with the neoplasms located in the rectum and amounts to 71 and 62.5% respectively. This high result can be most likely explained by the fact, that this department of colon contains a serious membrane, which distinctly separates the muscular layer from the abenteric organs and tissues. Also is noted that the serous membrane of the intestine is less subjected to penetration of the inflammatory infiltration, than the pararectal cellular tissue. The majority of mistake falls on the cases overestimated depth of the invasion at defining Phase T2.
These researches have noted that accuracy of diagnosing the phase of a tumoral process was higher in colonic intestine than in rectum. The greatest number of abscesses, inflammatory infiltration or radial therapy in the neoplasm area.
Damage regional lymph glands are an important prognostic factors in diagnosing rectum cancer. To define the capabilities of the method in diagnosing metastases in regional lymph glands, the results of the NLS method were damage with those of the pathomorphologic essay. In the letter the malignant damage to the regional lymph glands was detected in11 observation from 22 cases.
The analysis of the derived data proved that the NLS essay had correctly defined the pattern of damage to the lymph glands in 63.6% of cases.
The metastatic pattern of damage to the lymph nodes was defined in 74.8% of cases, and an inflammatory changes the results of ultrasonic colonoscopy and those of the pathomorphologic essay coincided only in 45,5% of observation. In 6 from 11 of cases the presence of metastasizes in lymph nodes was assumed (false-positive result). Such mistake s can be attributed to oncologic vigilance of the researcher and complexity of differential diagnostic of inflammatory and metastatically -altered lymph glands
1 NLS diagnostics is a highly efficient method of diagnosing the neoplasm of the colon, allowing to diagnose neoplasms and regional lymph glands.
2 The NLS method allows to detect the colon adenoma and cancer by presence or absence of the tumoral invasion in the intestinal wall.
3 The diagnostic efficiency of NLS method in defining the phase of tumoral process in the rectum is lower then in segmented intestine.
4 The diagnostical accuracy of the cancer phase in colon depends as much on the size as on the anatomic shape of the tumor growth. The best results were obtained at defining depth of invasion of the intestinal walls be a tumor sized under 2 cm and cover 5 cm.