New Potentials for NLS-Methods In Colonic Neoplasm Diagnosis

V.I. Nesterova, T.G. Kuznetsova,

V.I. Metlushko, N.L. Ogluzdina

Introduction

Colonoscopy is successfully used today to diagnose colon new growths. Based on a

number of indications endoscopic investigation provides reliable information about the

colonic growth surface in order to correctly classify its pattern and take a sample for

morphological identification. Yet, colonoscopy does not give an idea of the kind of

internal structure the new growth has, nor does it allow an assess the depth of the

invasion of the colon wall by a maligant tumor, determine its proliferation to adjacent

organs or metastases to regional lymph nodes. Besides, 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 a 4.9 GHz high frequency nonlinear sensor can help

clear up all of these issues.

The NLS-investigation provides information on intestinal wall layers and the adrectal

cellular tissue.

This research aimed to define the potentials of the NLS-method in a more specific

diagnostic of straight-and segmented intestine tumors.

The matter and investigation methods

87 patients were examined in whom 91 new growths were investigated using NLS

techniques. The examinees included 41 men and 46 women aged from 31 to 83 with

most of them (82%) aged 50 and over. All the patients affected by colon new growths

were subject to surgical treatment depending on the patient, size and location of the

growth. In 23 cases endoscopic polypectomy was performed. In 61 cases a resection was

undertaken on different parts of the colon and in 3 patients trans-anal endo-microsurgery

was performed. All of the NLS investigation results were verified by a

pathomorphological examination of macro preparations according to which the colonic new

growths were represented by simple tumors in 30 cases and by glandular cancers

with different degrees of differentiation in 61 cases.

The stages of the malignant process were defined according to TNM classification

adopted by the 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 in 5 patients (8%).

According to a patho-morphological examination, metastases into regional lymph nodes

were detected in 11 of 61 cases.

14All the patients underwent NLS-investigation and ultrasound colonoscopy to diagnose and

localize new growths, define their size, growth patterns and approximate

morphological characteristics together with ultrasound scanning of the abdominal cavity

and small pelvic organs to assess the condition of the organs adjacent to the colon and

diagnose distant metastases.

The NLS-investigation used a 4.9 GHz nonlinear sensor. The endoscopic

ultrasonography made use of the endoscopy ultrasonographic system UM-20 complete with

the ultrasonic colonoscope CF-UM20 (Olympus, Japan). The echographica 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 characteristics of the colon and

defines the number, localization and macroscopic characteristics of the new growth, and by

ultrasound scanning of the abdominal cavity as well. A thorough trans-abdominal

ultrasound scanning is required to assess the condition of the organs adjacent to the colon

and diagnose remote metastases.

A comparison of the NLS results with those of pathomorpholocal investigations was

made in order to define the potential of the NLS-method in differential diagnosis of

benign and malignant colonic new growths.

The results of the NLS-investigation coincided with the pathomorphological 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 observations noted

that difficulties in diagnosis were related to the deformation of intestinal wall layers due

to the pressure of a nodal villous tumor rather than to a genuine invasion. Two false-

negative results were obtained in the case of malignant adenoma and cancer diacrises.

Thus, the accuracy of the NLS method in differential diagnosis of malignant and benign

colon tumors amounted to 81.3% of sensitivity to 79.8%, while the specificity was 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 the patho-morphological

investigation data in 61 cases in order to assess the diagnostic efficiency of the

NLSmethod 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, where the data of NLS and patho-

15morphological 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 one case signs 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 under-statement of phase of the tumor process

occurred in one case and yet in one case no evidence of invasion proved to be found. The

analysis of the post surgical morphological conclusions revealed that in 6 of 7 false

positive results the patho-morphological investigation of a macro preparation detected a

deeper infiltration into the intestinal wall. However, according to microscopic

examination, the infiltration was of inflammatory rather than of a tumor kind. It should

also be noted that in all of the cases it had to do with an infiltrative tumor 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 understand better where there is imprecision in diagnosis, the efficiency of the

NLSmethod was analyzed in terms of the size, localization and form of germination of

neoplasms. The best results were obtained in diagnosing new growths sized under 2 cm and

over 5 cm.

Epithelial tumors over 5 cm in size is represented by phases T3 and T4 in 12 of 17 cases.

It has to be noted for large neoplasms the data of NLS assay did not coincide with patho-

morphologic data only in phase T2, where the process phase was overestimated because

of the presence of inflammatory infiltration in deeper layers, than the layers where the

tumor invasion occurred. Thus, at neoplasms larger than 5 cm in size the diagnosis of the

invasion degree of the intestinal wall correlates in 78.2% of observations. High

correlation was also obtained for depth of tumor 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 coincided with those of patho-morphologic conclusions in 76.7% of the

observations. It should also be noted, that tumors sized up to 2 cm are most convenient

for examination since they have the least number of artefacts.

In this study the greatest group was the tumors sized from 2 to 5 cm, where the results

proved to be lower, than in two first groups. The NLS data and those of the patho-

morphologic essays coincided in 66.7% of cases. An appreciable error band (60%)

occurred in phase T2, where the intestinal wall invasion depth was overestimated in all

observations.

The great value has the fact, that according to pathomorphologic essay, in 5 of 6 cases of

hyper-diagnosis apart from the tumor 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 a 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. A differential diagnosis of the

tumor infiltration depth in these phases is complex.

16At 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 tumor invasion in the

intestinal wall. All neoplasms were classified into three groups. In function of the shape of

the tumor growth: polypiform, saucer-shaped and infiltrative.

The highest results were obtained when diagnosing the phase of the saucer-shaped

growth cancer process where the accuracy of defining the tumor invasion in the intestinal

wall was 78.3%.

It seems however possible to fully estimate the accuracy of the NLS method in defining

the depth of a tumor invasion at neoplasms with saucer-shaped growth because of its

dismal occurrence among other forms of patients surveyed by us.

The polypiform 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 conditions for the survey. The

accuracy of NLS method in defining the depth of tumor invasion in the intestinal wall

was as high as 65%. It has to be noted, that half of all cases divergent with the

pathomorphologic conclusions is due to the overestimated depth of tumor infiltration at

defining the phase T2, which is connected with the presence of a perifocal inflammation.

This fact suggests difficulties in defining the phase of a cancer process in cases where the

tumor invasion is compounded by the inflammatory component penetrating deeper layers

of the intestinal wall and beyond its limits.

The neoplasms with an infiltrative growth shape have proved to be most difficult in

defining the degree of the tumor invasion into the intestinal wall. In this this group the

results 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 we 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 tumor process in the colonic

intestine is significantly higher, than at finding the tumor 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

serous membrane, which distinctly separates the muscular layer from the abenteric organs

and tissues. Also it is noted, that the serous membrane of the intestine is less subject to

penetration of the inflammatory infiltration, than the para-rectal cellular tissue. The

majority discrepancy relates to over-estimated depth of the invasion at defining Phase T2.

These researchers have noted that the accuracy of diagnosing the phase of a tumor

process was higher in colonic intestine, than in rectum. The greatest number of

17discrepancies occurs in Phase T2, which is conditioned by the presence of abscesses,

inflammatory infiltration or radial therapy in the neoplasm area.

Damaged regional lymph glands are an important prognostic factor 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 compared with those of the pathomorphologic

essay. In the latter the malignant damage to the regional lymph glands was detected in 11

observations 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

in inflammatory changes the results of the ultrasonic colonoscopy and those of the patho-

morphologic essay coincided only in 45.5% of observations. In 6 from 11 of cases the

presence of metastasizes in lymph nodes was assumed (false-positive result). Such

mistakes can be attributed to oneologic vigilance of the researcher and complexity of

differential diagnosis of inflammatory and metastatically-altered lymph glands.

Conclusions

1. NLS diagnosis is a highly efficient method of diagnosing the neoplasms of the colon,

allowing to diagnose neoplasms and regional lymph glands.

2. The NLS method enables to detect the colon adenoma and cancer by the presence or

absence of the tumor invasions in the intestinal wall.

3. The diagnostic efficiency of NLS method in defining the phase of tumor process in the

rectum is lower, than in segmented intestine.

4. The diagnostic 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 by a tumor sized under 2 cm and

over 5 cm.