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The importance of parametrial lymph nodes in the treatment of cervical cancer
GYNECOLOGIC
ONCOLOGY
34,
206-2 I 1 ( 1989)
The Importance of Parametrial Lymph Nodes in the Treatment of Cervical Cancer FRANK GIRARDI, Department
M.D., WERNER LICHTENEGGER, M.D., KARL TAMUSSINO, M.D., AND JOSEF HAAS, M.S. of Obstetrics
and Gynecology,
University
of Graz, Auenbruggerplatz
14, A-8010 Graz, Austria
Received May 19, 1988
This study aimed to determine the presence, distribution, and metastatic involvement of lymph nodes in the parametria of patients undergoing radical hysterectomy for cervical cancer. Parametrial nodes were present in the giant sections of 280 (78%) of 359 surgical specimens, and me&statically involved nodes were found in 63 (22.5%) of these 280. Both positive and negative nodes were distributed through the entire parametrium. The frequency of positive nodes was linearly associated with both the clinical stage and with the tumor volume. The recurrence rate was higher when the parametrial nodes were positive than when they were negative. Survival dropped when the parametrial nodes were positive, regardless of the clinical stage. o 1989 Academic PKSS, Inc.
Pelvic lymphadenectomy as a curative as well as diagnostic measure in the surgical treatment of cervical cancer was first proposed by Ries in 1895 [ 1,2]. Today it is performed routinely at many centers, while at others lymph nodes are only sampled for staging purposes. The primarily lymphogenous spread of cervical cancer is the pathologic and anatomic reason for therapeutic lymphadenectomy. Tumor cells reach the regional nodes at the pelvic wall, where they can metastasize, via the lymphatics in the parametria. The frequency of regional node involvement is associated with the size of the primary tumor [3-121. The anatomic distribution and metastatic involvement of parametrial lymph nodes have been controversial. According to Plentl and Friedman [ 131, a small node called the parauterine node where the uterine artery crosses the ureter was first described by Lucas-Champonniere in 1870, and was also reported by other early investigators such as Sappey [14] and Bruhns [15]. Kroemer [I61 described several small nodes occurring with regularity, but attached no great importance to them. Kundrat [I71 and Brunet [18] also described similar structures, but Langreder [19] made no mention of any nodes in a detailed monograph on the parametria. Baltzer [4]
reported an association between tumor size and metastasis to the pelvic nodes, but did not mention parametrial node involvement. Reiffenstuhl [20] described only the parauterine node in the parametria and found it to vary greatly in size. Plentl and Friedman [ 131 consider it an intercalate node which enlarges under pathologic conditions. Henriksen [21] described 69 metastatically involved parametrial and paracervical nodes in 41 patients with advanced cervical cancer at autopsy. In an autopsical analysis of 107 cases of cervical cancer, 89 (83%) of which were in stage IV, Holzaepfel and Ezell [221 found involvement of the parauterine node or of small nodes along the major lymphatic trunks transversing the parametrium in 78 (73%). By studying surgical specimens processed according to the method described by Burghardt and Pickel [6-81, we have been able to delineate the frequency, distribution, metastatic involvement, and clinical importance of the parametrial lymph nodes. We found that direct, continuous spread of cervical cancer into the parametria is less common than previously assumed. Isolated tumor cell deposits were found in the parametrial lymphatics as were deposits without any apparent relationship to anatomic structures. However, considering the overall involvement of the parametria in cervical cancer, metastases are most often located in the lymph nodes [71.
206 W’O-8258/89 $1.50 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
MATERIALS AND METHODS Between 1971 and 1986, 359 specimens obtained at radical abdominal hysterectomy were studied. There were 132 cases of clinical stage Ib, 8 of stage IIa, and 219 of stage IIb cervical cancer. The individual specimen was fixed as a whole with the parametria spread out. The uterine corpus was removed and the cervix divided frontally with the parametria in the sectional plane. The specimen was embedded in a paraffin block of which a series of giant sections 8 to 10 pm thick were made.
PARAMETRIAL
LYMPH
NODES
IN CERVICAL
CANCER
207
is significant in both stages (P < .05). There were too few stage IIa cases for statistical analysis. Figures 5 and 6 relate the survival curves to tumor size and parametrial node involvement. Depending on the tumor size, the 5-year survival rates lay between 64.9% and 91.8% when nodes were negative but between 43.8% and 63.1% when nodes were positive. Among the patients with positive parametrial nodes, those with the largest tumors had an insignificantly better survival rate than those with somewhat smaller tumors. The reason for this is unclear. The results of the patients with the smallest tumors are not comparable because their number is too small. In 12 patients with positive parametrial nodes, the regional pelvic nodes were free of metastatic involvement (Table 3). Two of these women died: 1 after 72 months of a recurrence at the left pelvic wall and invading the rectum, and another after 84 months of invasive stage II vulvar cancer that appeared 4 years after radical hysterectomy. One patient developed a carcinoma in situ in the vaginal vault and was treated successfully with raRESULTS diotherapy. Six of the 12 patients underwent postoperParametrial nodes were found in 280 (78%) of the 359 ative radiotherapy and 1 had combination chemotherapy. surgical specimens; metastatically involved nodes were Figure 7 shows the location of the positive parametrial found in 63 (22.5%) of these 280 (Table 1). Of the cases nodes in the 12 patients and specifically in the 2 with with positive nodes, 44.4% were in the medial part of recurrence. the parametrium near the cervix, 38.1% were in the lateral part near the pelvic wall, and 17.5% in both parts. DISCUSSION Figure 2 is a schematic analysis of 60 cases with positive parametrial nodes. Both positive and negative nodes Previous data from precise morphometric evaluation were scattered throughout the parametria. of surgical specimens suggest the superiority of surgical Positive parametrial lymph nodes were found in 11.4% treatment of cervical cancer, especially in tumors with of stage Ib and in 21.5% of stage IIb specimens (Table a large volume or in stage IIb [7,8]. The aim of surgery is to remove both the primary tumor and its deposits as 2). The metastatic involvement of the pelvic nodes27.3% in stage Ib and 40.6% in stage IIb-showed a completely as possible. In cervical cancer, tumor desimilar increase according to stage. The incidence of posits occur mainly in the pelvic lymph nodes, but also positive parametrial nodes is linearly associated with the in the paraaortic nodes. Consequently, we have in the tumor size expressed as the quotient of tumor area and last 2 years extended lymphadenectomy to the paraaortic nodes in stage IIb cervical cancer and in stage Ib if cervical area (Fig. 3). During a follow-up period of 12 to 204 months, disease positive pelvic nodes are found at surgery [23]. recurred in 114 (31.8%) of 359 patients. Parametrial In contrast to staging laparotomy as performed at other nodes were positive in 37 (32.5%) of these 114. In the centers [24-261, lymphadenectomy as described above 245 patients free of recurrence, positive parametrial aims to cure. This concept is not new but has again nodes were found in only 26 (10.6%). Accordingly, the become controversial. Especially the fact that the lym5-year survival rate lay between 81.7% and 55.9%, de- phatic drainage of the cervix runs through the parametria pending on the involvement of the parametrial nodes. to the pelvic sidewall, and that the parametria can thus Figure 4 shows the survival rates with respect to clinical contain the first deposits of discontinuous tumor spread, stage and parametrial node involvement. In patients with has not received due attention. This study shows not negative parametrial nodes, the 5-year surviv’al rates in only that lymph nodes are often found in the parametria stage Ib and IIb were 85.7% and 80.7%, respectively, of patients with cervical cancer, but that these nodes are and thus did not differ significantly. But when the para- often positive. Both positive and negative nodes are dismenial nodes were positive, the 5-year survival figures tributed completely unevenly through the parametria bedropped to 60.6% and 54.0%, respectively. This decrease tween the cervix and the pelvic wall. Positive nodes can
Depending on the size of the cervix, a surgical specimen produced six to ten giant sections. A single section is not representative of the whole parametrium. The axes of the sectional plane are the cervical canal and the parametria. The specimens were stained with hematoxylin-eosin. In the histologic section, parametrial nodes of different sizes are visible even to the naked eye (Fig. 1). All nodes were examined microscopically for metastatic involvement. The ‘naked eye can also discern the size of the cervical tumor, the greatest area of which was mea-. sured and related to the size of the cervix. Tumor size was determined with a semiautomatic image analyzer. The circumference of the tumor was traced on a digitizer tablet superimposed on a representative giant section. The size of the cervix was determined by the same technique. The quotient of tumor area and cervical area expresses the percentage of cervical volume occupied by the tumor and is a parameter of disease spread and a significant prognostic factor [7,8].
208
GIRARDI ET AL.
FIG. 1. Giant sections of two specimens obtained at radical hysterectomy (H + E). (a) Two positive nodes can be seen near me C~JVM (b) One positive node near the pelvic wall.
PARAMETRIAL
LYMPH NODES IN CERVICAL
TABLE 2 Parametrial and Pelvic Lymph Node Involvement According to Clinical Stage
TABLE 1 Number and Distribution of Positive and Negative Parametrial Lymph Nodes in 359 Specimens Obtained at Radical Hysterectomy for Cervical Cancer Number
Percent
Specimens with parametrial nodes present
280
78.0
Near the cervix Near the pelvic wall Both
69 86 125
24.6 30.7 44.6
Negative parametrial nodes Positive parametrial nodes
217 63
77.5 22.5
28 24 I1
44.4 38.1 17.5
Pos. nodes near the cervix Pos. nodes near the pelvic wall Both
209
CANCER
Stage IB N = 132
HA N=8
IIB N = 219
Total N = 359
Parametrial nodes
15 11.4%
1 12.5%
47 21.5%
63
Pelvic nodes
36 27.3%
2 25%
89 40.6%
127
10
be found even in the most lateral portion of the parametria. Radical surgery should thus not just transect the parametria but resect them as close to the pelvic sidewall as possible [23]. The percentage of positive nodes in the parametria increases both with the measured size of the tumor and with the clinical stage. Figure 3 shows that parametrial nodes can be positive, albeit less frequently, even with small tumors comprising less than 20% of the cervical volume. With the largest tumors in our series, the incidence of positive nodes rose to about 35%. The question whether limited surgical radicality suffices for smaller tumors remains open. Parametrial node involvement correlates with involvement of the nodes at the pelvic wall insofar as that the pelvic nodes will be negative in 74% of patients with negative parametrial nodes. Conversely, the pelvic nodes will be positive in 81% of patients with positive parametrial nodes. The relationship between parametrial node involve-
so 3
POSITIVE 0
N=
20
PARAMETRIAL 63
40
NODES
60
60
100
TUMOR/CERVIX-QUOTIENT PIG. 3. Relationship between tumor size and parametrial node involvement in 359 patients.
M
60
l POSITIVE NOQES 0 NEGATIVE NODES
\
40 -
3. _ STAGE
10 -
0
PIG. 2. Schematic analysis of nodal distribution in 60 specimens with positive parametrial nodes (stars).
I 0
\
t t , I '---------------------A
50 -
20 -
\
\
-
0 LNA LN+ LNXLN*Ib 0 LN+ + LN+
'
-
4
60.6% 54.0% 42.9%
8 PARAM. NODES I b II CI II b II II
1
k
\
a b
N=116 N= 7 N.169 NV 15 N= 1 N= 46
2
3
4
I 5
SURVIVAL. Years PIG. 4. Survival rates according to clinical stage and parametrial node involvement.
210
CXRARDI ET AL.
0 6
\ __-----
: 60 2 > so75 40a A i + 10 X 1 0 0 I 0
20
0 -20% 21-40X 41-60X 61-i& al%
N= N= N. N. N-
3
SURVIVAL,
0
Years
\ ----
-x
43.6%
40
0
I 0
21-40X 41-60X 61-80X Elx I '1
Nodes N= N= N= N= N-
8 Ouotien:
2 7 14 23 16
2
3
SURVIVAL.
I 5
4
FIG. 7. Location of positive and negative parametrial nodes in 12 patients with negative pelvic nodes.
ment, survival, and the recurrence-free interval can be seen in Fig. 4. Of course, the status of the parametrial nodes is a certain indicator of the status of the nodes at the pelvic wall (Table 3). But if the parametria are the only site of positive nodes, radical abdominal hysterectomy with en bloc excision of the parametria at the pelvic wall can be expected to cure the patient. In 12 such patients, invasive tumor recurred in 1. The carcinoma in situ of the remaining vagina can hardly be related to node involvement, and 1 patient died of a vulvar cancer 84 months after surgery for cervical cancer. In cervical cancer, the frequent involvement of parametrial lymph nodes that can be located anywhere in the parametria demands total excision of the parametria at radical hysterectomy. If lymphadenectomy is to be curative, it seems pointless to leave that part of the lymphatic drainage of the cervix in situ through which metastatic tumor cells must pass.
--.
SO
A + X 0
POLNODES PATIENT
I 5
4
FIG. 5. Survival according to tumor size of patients with negative parametrial nodes.
Positive 0 0 -20%
'~oK:P:K
55 66 77 64 30
2
1
64.9%
8 Quotient
Nodes
~JJ30- Negative
-0
01 NEGATIVE NODES
Years
FIG. 6. Survival according to tumor size of patients with positive parametrial nodes..
REFERENCES 1. Ries, E. Eine neue Operationsmethode des Uteruskarzinoms, Z. Geburth.
TABLE 3 Association between Parametrial Node Involvement and Pelvic Node Involvement Pelvic nodes Parametrial nodes
Neg.
Pos.
Total
Negative
219 14%
77 26%
296
12 19%
51 81%
63
Positive
Gyniik.
32, 266-274 (1895).
2. Ries, E. Eine neue Operationsmethode des Uteruskarzinoms, Z. Geburth. Gyntik. 37, 518-532 (1897). 3. Baltzer, J., Kopcke, W., Lohe, K. J., Kaufmann, C., Ober, K. G., and Zander, J. Die operative Behandlug des Zervixkarzinoms, Geburtsh. u. Fruuenheilk. 44, 279-285 (1984). 4. Baltzer, J., and Kopcke, W. Tumor size and lymph node metastases in squamous cell carcinoma of the uterine cervix, Arch. Gynecol. 227, 271 (1979). 5. Brunschwig, A. Surgical treatment of stage I cancer of the cervix, Cancer 13, 34 (1960).
359
6. Burghardt, E., and Pickel, H. Local spread and lymph node involvement in cervical cancer, Obstet. Gynecol. 52, 138 (1978). 7. Burghardt, E., Pickel, H., and Haas, J. Prognostische Faktoren und operative Behandlung des Zervixkarzinoms, in Spezielle Gy-
PARAMETRIAL
LYMPH NODES IN CERVICAL
und Geburtshilfe (E. Burghardt, Ed.), Springer, Vienna, 1st ed., p. 72 (1985). 8. Burghardt, E., Pickel, H., Haas, J., and Lahousen, M. Prognostic factors and operative treatment of stages Ib to IIb cervical cancer, Amer. J. Obstet. Gynecol. 156, 988-996 (1987). 9. Huhn, F. 0. Die Lymphknotenvetinderngen beim Zervixkarzinom und die Beziehungen TumorgriiDe und lymphogene Tumorausbreitung, Habilitationsschrift, Med. Fak. Univ. Kiiln, 82 ndkologie
(1964).
10. Kindermann, E., and Ober, K. G. Ausbreitung des Zervixkrebses, in Gyniikologie und Geburtshilfe (0. KPser, Ed.), Thieme, Stuttgart, p. 432 (1972). 11. Piver, M. S., and Chiung, W. S. Prognostic significance of cervical lesion size and pelvic node metastases in cervical carcinoma, Obstet. Gynecol. 46, 507 (1975). 12. Shingleton, H. M., Gore, H., Soong, S. J., and Ort, J. W. Tumor recurrence and survival in stage Ib cancer of the cervix, Amer. J. C/in. Oncof. 6, 265 (1983). 13. Plentl, A. A., and Friedman, E. A. Lymphatic system of the female genitalia, in Major problems in obstetrics and gynecology (E. A. Friedman, Ed.), Saunders, Philadelphia, Vol. 2, pp. 75-l 15 (1971). Descriptive, A, Delahaye, 14. Sappey, P. C. Trait6 d’dnatomique Paris, p. 6% (1889). 15. Bruhns, C. Uber die LymphgefaBe des weiblichen Genitale nebst einigen Bemerkungen iiber die Topographie der Leistendriisen, Arch.
f. Anat. u. Entwicklungsgeschichte,
57 (1898).
16. Kroemer, P. Die Lymphorgane der weiblichen Genitale und ihre Veranderungen bei malignen Erkrankungen des Uterus, Arch. Gyndk. 69, 355-409 (1903). 17. Kundrat, R. Uber die Ausbreitung des Karzinoms im parame-
CANCER
211
tranen Gewebe beim Krebs des Collum uteri, Arch. Gyndk. 69, 355-409 (1903). 18. Brunet, G. Ergebnisse der abdominellen Radikaloperation des Gebihmutterscheidenkrebses mittels Laparotomia hypogestica, Z. Geburtsh. Gym&l. 56, 1 (1905). 19. Langreder, W. Das Parametrium. Funktionelle Anatomie der Ligamentziige sowie ihre Beziehung zur Zervix und Beckenwand besonders wiihrend der Schwangerschaft und Geburt, Thieme, Le-
ipzig (1955). 20. Reiffenstuhl, G. Das Lymphsystem des weiblichen Genitale, Urban & Schwarzenberg, Vienna, pp. 31-34 (1957). 21. Hemiksen, E. The lymphatic spread of carcinoma of the cervix and of the body of the uterus, Amer. J. Obstet. Gynecol. 58, 924 (1949). 22. Holzaepfel, J. H., and Ezell, H. E. Sites of metastases of uterine carcinoma, Amer. J. Obstet. Gynecol. 69, 1027-1036 (1955). 23. Burghardt, E., and Winter, R. Die abdominelle Radikaloperation des Zervixkarzinoms mit pelviner und paraortaler Lymphadenektomie, Film (1987). 24. Piver, M. S. The value of pretherapy paraaortic lymphadenectomy for carcinoma of the cervix uteri, Surg. Gynecol. Obstet. 145, 1718 (1977). 25. Piver, M. S., Barlow, J. J., and Krishnamsetty, R. Five-year survival (NED) in patients with biopsy confirmed aortic node metastasis from cervical carcinoma, Amer. J. Obstet. Gynecol. 139,474478 (1981). 26. Welander, C. E., Pierce, V. K., Nori, D., Hilaris, B. S., Kosloff, C., Clark, D. G., Jones, W. B., Kim, W. S., and Lewis, J. L., Jr. Pretreatment laparotomy in carcinoma of the cervix, Gynecol. Oncol. 12, 336-347 (1981).
ONCOLOGY
34,
206-2 I 1 ( 1989)
The Importance of Parametrial Lymph Nodes in the Treatment of Cervical Cancer FRANK GIRARDI, Department
M.D., WERNER LICHTENEGGER, M.D., KARL TAMUSSINO, M.D., AND JOSEF HAAS, M.S. of Obstetrics
and Gynecology,
University
of Graz, Auenbruggerplatz
14, A-8010 Graz, Austria
Received May 19, 1988
This study aimed to determine the presence, distribution, and metastatic involvement of lymph nodes in the parametria of patients undergoing radical hysterectomy for cervical cancer. Parametrial nodes were present in the giant sections of 280 (78%) of 359 surgical specimens, and me&statically involved nodes were found in 63 (22.5%) of these 280. Both positive and negative nodes were distributed through the entire parametrium. The frequency of positive nodes was linearly associated with both the clinical stage and with the tumor volume. The recurrence rate was higher when the parametrial nodes were positive than when they were negative. Survival dropped when the parametrial nodes were positive, regardless of the clinical stage. o 1989 Academic PKSS, Inc.
Pelvic lymphadenectomy as a curative as well as diagnostic measure in the surgical treatment of cervical cancer was first proposed by Ries in 1895 [ 1,2]. Today it is performed routinely at many centers, while at others lymph nodes are only sampled for staging purposes. The primarily lymphogenous spread of cervical cancer is the pathologic and anatomic reason for therapeutic lymphadenectomy. Tumor cells reach the regional nodes at the pelvic wall, where they can metastasize, via the lymphatics in the parametria. The frequency of regional node involvement is associated with the size of the primary tumor [3-121. The anatomic distribution and metastatic involvement of parametrial lymph nodes have been controversial. According to Plentl and Friedman [ 131, a small node called the parauterine node where the uterine artery crosses the ureter was first described by Lucas-Champonniere in 1870, and was also reported by other early investigators such as Sappey [14] and Bruhns [15]. Kroemer [I61 described several small nodes occurring with regularity, but attached no great importance to them. Kundrat [I71 and Brunet [18] also described similar structures, but Langreder [19] made no mention of any nodes in a detailed monograph on the parametria. Baltzer [4]
reported an association between tumor size and metastasis to the pelvic nodes, but did not mention parametrial node involvement. Reiffenstuhl [20] described only the parauterine node in the parametria and found it to vary greatly in size. Plentl and Friedman [ 131 consider it an intercalate node which enlarges under pathologic conditions. Henriksen [21] described 69 metastatically involved parametrial and paracervical nodes in 41 patients with advanced cervical cancer at autopsy. In an autopsical analysis of 107 cases of cervical cancer, 89 (83%) of which were in stage IV, Holzaepfel and Ezell [221 found involvement of the parauterine node or of small nodes along the major lymphatic trunks transversing the parametrium in 78 (73%). By studying surgical specimens processed according to the method described by Burghardt and Pickel [6-81, we have been able to delineate the frequency, distribution, metastatic involvement, and clinical importance of the parametrial lymph nodes. We found that direct, continuous spread of cervical cancer into the parametria is less common than previously assumed. Isolated tumor cell deposits were found in the parametrial lymphatics as were deposits without any apparent relationship to anatomic structures. However, considering the overall involvement of the parametria in cervical cancer, metastases are most often located in the lymph nodes [71.
206 W’O-8258/89 $1.50 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
MATERIALS AND METHODS Between 1971 and 1986, 359 specimens obtained at radical abdominal hysterectomy were studied. There were 132 cases of clinical stage Ib, 8 of stage IIa, and 219 of stage IIb cervical cancer. The individual specimen was fixed as a whole with the parametria spread out. The uterine corpus was removed and the cervix divided frontally with the parametria in the sectional plane. The specimen was embedded in a paraffin block of which a series of giant sections 8 to 10 pm thick were made.
PARAMETRIAL
LYMPH
NODES
IN CERVICAL
CANCER
207
is significant in both stages (P < .05). There were too few stage IIa cases for statistical analysis. Figures 5 and 6 relate the survival curves to tumor size and parametrial node involvement. Depending on the tumor size, the 5-year survival rates lay between 64.9% and 91.8% when nodes were negative but between 43.8% and 63.1% when nodes were positive. Among the patients with positive parametrial nodes, those with the largest tumors had an insignificantly better survival rate than those with somewhat smaller tumors. The reason for this is unclear. The results of the patients with the smallest tumors are not comparable because their number is too small. In 12 patients with positive parametrial nodes, the regional pelvic nodes were free of metastatic involvement (Table 3). Two of these women died: 1 after 72 months of a recurrence at the left pelvic wall and invading the rectum, and another after 84 months of invasive stage II vulvar cancer that appeared 4 years after radical hysterectomy. One patient developed a carcinoma in situ in the vaginal vault and was treated successfully with raRESULTS diotherapy. Six of the 12 patients underwent postoperParametrial nodes were found in 280 (78%) of the 359 ative radiotherapy and 1 had combination chemotherapy. surgical specimens; metastatically involved nodes were Figure 7 shows the location of the positive parametrial found in 63 (22.5%) of these 280 (Table 1). Of the cases nodes in the 12 patients and specifically in the 2 with with positive nodes, 44.4% were in the medial part of recurrence. the parametrium near the cervix, 38.1% were in the lateral part near the pelvic wall, and 17.5% in both parts. DISCUSSION Figure 2 is a schematic analysis of 60 cases with positive parametrial nodes. Both positive and negative nodes Previous data from precise morphometric evaluation were scattered throughout the parametria. of surgical specimens suggest the superiority of surgical Positive parametrial lymph nodes were found in 11.4% treatment of cervical cancer, especially in tumors with of stage Ib and in 21.5% of stage IIb specimens (Table a large volume or in stage IIb [7,8]. The aim of surgery is to remove both the primary tumor and its deposits as 2). The metastatic involvement of the pelvic nodes27.3% in stage Ib and 40.6% in stage IIb-showed a completely as possible. In cervical cancer, tumor desimilar increase according to stage. The incidence of posits occur mainly in the pelvic lymph nodes, but also positive parametrial nodes is linearly associated with the in the paraaortic nodes. Consequently, we have in the tumor size expressed as the quotient of tumor area and last 2 years extended lymphadenectomy to the paraaortic nodes in stage IIb cervical cancer and in stage Ib if cervical area (Fig. 3). During a follow-up period of 12 to 204 months, disease positive pelvic nodes are found at surgery [23]. recurred in 114 (31.8%) of 359 patients. Parametrial In contrast to staging laparotomy as performed at other nodes were positive in 37 (32.5%) of these 114. In the centers [24-261, lymphadenectomy as described above 245 patients free of recurrence, positive parametrial aims to cure. This concept is not new but has again nodes were found in only 26 (10.6%). Accordingly, the become controversial. Especially the fact that the lym5-year survival rate lay between 81.7% and 55.9%, de- phatic drainage of the cervix runs through the parametria pending on the involvement of the parametrial nodes. to the pelvic sidewall, and that the parametria can thus Figure 4 shows the survival rates with respect to clinical contain the first deposits of discontinuous tumor spread, stage and parametrial node involvement. In patients with has not received due attention. This study shows not negative parametrial nodes, the 5-year surviv’al rates in only that lymph nodes are often found in the parametria stage Ib and IIb were 85.7% and 80.7%, respectively, of patients with cervical cancer, but that these nodes are and thus did not differ significantly. But when the para- often positive. Both positive and negative nodes are dismenial nodes were positive, the 5-year survival figures tributed completely unevenly through the parametria bedropped to 60.6% and 54.0%, respectively. This decrease tween the cervix and the pelvic wall. Positive nodes can
Depending on the size of the cervix, a surgical specimen produced six to ten giant sections. A single section is not representative of the whole parametrium. The axes of the sectional plane are the cervical canal and the parametria. The specimens were stained with hematoxylin-eosin. In the histologic section, parametrial nodes of different sizes are visible even to the naked eye (Fig. 1). All nodes were examined microscopically for metastatic involvement. The ‘naked eye can also discern the size of the cervical tumor, the greatest area of which was mea-. sured and related to the size of the cervix. Tumor size was determined with a semiautomatic image analyzer. The circumference of the tumor was traced on a digitizer tablet superimposed on a representative giant section. The size of the cervix was determined by the same technique. The quotient of tumor area and cervical area expresses the percentage of cervical volume occupied by the tumor and is a parameter of disease spread and a significant prognostic factor [7,8].
208
GIRARDI ET AL.
FIG. 1. Giant sections of two specimens obtained at radical hysterectomy (H + E). (a) Two positive nodes can be seen near me C~JVM (b) One positive node near the pelvic wall.
PARAMETRIAL
LYMPH NODES IN CERVICAL
TABLE 2 Parametrial and Pelvic Lymph Node Involvement According to Clinical Stage
TABLE 1 Number and Distribution of Positive and Negative Parametrial Lymph Nodes in 359 Specimens Obtained at Radical Hysterectomy for Cervical Cancer Number
Percent
Specimens with parametrial nodes present
280
78.0
Near the cervix Near the pelvic wall Both
69 86 125
24.6 30.7 44.6
Negative parametrial nodes Positive parametrial nodes
217 63
77.5 22.5
28 24 I1
44.4 38.1 17.5
Pos. nodes near the cervix Pos. nodes near the pelvic wall Both
209
CANCER
Stage IB N = 132
HA N=8
IIB N = 219
Total N = 359
Parametrial nodes
15 11.4%
1 12.5%
47 21.5%
63
Pelvic nodes
36 27.3%
2 25%
89 40.6%
127
10
be found even in the most lateral portion of the parametria. Radical surgery should thus not just transect the parametria but resect them as close to the pelvic sidewall as possible [23]. The percentage of positive nodes in the parametria increases both with the measured size of the tumor and with the clinical stage. Figure 3 shows that parametrial nodes can be positive, albeit less frequently, even with small tumors comprising less than 20% of the cervical volume. With the largest tumors in our series, the incidence of positive nodes rose to about 35%. The question whether limited surgical radicality suffices for smaller tumors remains open. Parametrial node involvement correlates with involvement of the nodes at the pelvic wall insofar as that the pelvic nodes will be negative in 74% of patients with negative parametrial nodes. Conversely, the pelvic nodes will be positive in 81% of patients with positive parametrial nodes. The relationship between parametrial node involve-
so 3
POSITIVE 0
N=
20
PARAMETRIAL 63
40
NODES
60
60
100
TUMOR/CERVIX-QUOTIENT PIG. 3. Relationship between tumor size and parametrial node involvement in 359 patients.
M
60
l POSITIVE NOQES 0 NEGATIVE NODES
\
40 -
3. _ STAGE
10 -
0
PIG. 2. Schematic analysis of nodal distribution in 60 specimens with positive parametrial nodes (stars).
I 0
\
t t , I '---------------------A
50 -
20 -
\
\
-
0 LNA LN+ LNXLN*Ib 0 LN+ + LN+
'
-
4
60.6% 54.0% 42.9%
8 PARAM. NODES I b II CI II b II II
1
k
\
a b
N=116 N= 7 N.169 NV 15 N= 1 N= 46
2
3
4
I 5
SURVIVAL. Years PIG. 4. Survival rates according to clinical stage and parametrial node involvement.
210
CXRARDI ET AL.
0 6
\ __-----
: 60 2 > so75 40a A i + 10 X 1 0 0 I 0
20
0 -20% 21-40X 41-60X 61-i& al%
N= N= N. N. N-
3
SURVIVAL,
0
Years
\ ----
-x
43.6%
40
0
I 0
21-40X 41-60X 61-80X Elx I '1
Nodes N= N= N= N= N-
8 Ouotien:
2 7 14 23 16
2
3
SURVIVAL.
I 5
4
FIG. 7. Location of positive and negative parametrial nodes in 12 patients with negative pelvic nodes.
ment, survival, and the recurrence-free interval can be seen in Fig. 4. Of course, the status of the parametrial nodes is a certain indicator of the status of the nodes at the pelvic wall (Table 3). But if the parametria are the only site of positive nodes, radical abdominal hysterectomy with en bloc excision of the parametria at the pelvic wall can be expected to cure the patient. In 12 such patients, invasive tumor recurred in 1. The carcinoma in situ of the remaining vagina can hardly be related to node involvement, and 1 patient died of a vulvar cancer 84 months after surgery for cervical cancer. In cervical cancer, the frequent involvement of parametrial lymph nodes that can be located anywhere in the parametria demands total excision of the parametria at radical hysterectomy. If lymphadenectomy is to be curative, it seems pointless to leave that part of the lymphatic drainage of the cervix in situ through which metastatic tumor cells must pass.
--.
SO
A + X 0
POLNODES PATIENT
I 5
4
FIG. 5. Survival according to tumor size of patients with negative parametrial nodes.
Positive 0 0 -20%
'~oK:P:K
55 66 77 64 30
2
1
64.9%
8 Quotient
Nodes
~JJ30- Negative
-0
01 NEGATIVE NODES
Years
FIG. 6. Survival according to tumor size of patients with positive parametrial nodes..
REFERENCES 1. Ries, E. Eine neue Operationsmethode des Uteruskarzinoms, Z. Geburth.
TABLE 3 Association between Parametrial Node Involvement and Pelvic Node Involvement Pelvic nodes Parametrial nodes
Neg.
Pos.
Total
Negative
219 14%
77 26%
296
12 19%
51 81%
63
Positive
Gyniik.
32, 266-274 (1895).
2. Ries, E. Eine neue Operationsmethode des Uteruskarzinoms, Z. Geburth. Gyntik. 37, 518-532 (1897). 3. Baltzer, J., Kopcke, W., Lohe, K. J., Kaufmann, C., Ober, K. G., and Zander, J. Die operative Behandlug des Zervixkarzinoms, Geburtsh. u. Fruuenheilk. 44, 279-285 (1984). 4. Baltzer, J., and Kopcke, W. Tumor size and lymph node metastases in squamous cell carcinoma of the uterine cervix, Arch. Gynecol. 227, 271 (1979). 5. Brunschwig, A. Surgical treatment of stage I cancer of the cervix, Cancer 13, 34 (1960).
359
6. Burghardt, E., and Pickel, H. Local spread and lymph node involvement in cervical cancer, Obstet. Gynecol. 52, 138 (1978). 7. Burghardt, E., Pickel, H., and Haas, J. Prognostische Faktoren und operative Behandlung des Zervixkarzinoms, in Spezielle Gy-
PARAMETRIAL
LYMPH NODES IN CERVICAL
und Geburtshilfe (E. Burghardt, Ed.), Springer, Vienna, 1st ed., p. 72 (1985). 8. Burghardt, E., Pickel, H., Haas, J., and Lahousen, M. Prognostic factors and operative treatment of stages Ib to IIb cervical cancer, Amer. J. Obstet. Gynecol. 156, 988-996 (1987). 9. Huhn, F. 0. Die Lymphknotenvetinderngen beim Zervixkarzinom und die Beziehungen TumorgriiDe und lymphogene Tumorausbreitung, Habilitationsschrift, Med. Fak. Univ. Kiiln, 82 ndkologie
(1964).
10. Kindermann, E., and Ober, K. G. Ausbreitung des Zervixkrebses, in Gyniikologie und Geburtshilfe (0. KPser, Ed.), Thieme, Stuttgart, p. 432 (1972). 11. Piver, M. S., and Chiung, W. S. Prognostic significance of cervical lesion size and pelvic node metastases in cervical carcinoma, Obstet. Gynecol. 46, 507 (1975). 12. Shingleton, H. M., Gore, H., Soong, S. J., and Ort, J. W. Tumor recurrence and survival in stage Ib cancer of the cervix, Amer. J. C/in. Oncof. 6, 265 (1983). 13. Plentl, A. A., and Friedman, E. A. Lymphatic system of the female genitalia, in Major problems in obstetrics and gynecology (E. A. Friedman, Ed.), Saunders, Philadelphia, Vol. 2, pp. 75-l 15 (1971). Descriptive, A, Delahaye, 14. Sappey, P. C. Trait6 d’dnatomique Paris, p. 6% (1889). 15. Bruhns, C. Uber die LymphgefaBe des weiblichen Genitale nebst einigen Bemerkungen iiber die Topographie der Leistendriisen, Arch.
f. Anat. u. Entwicklungsgeschichte,
57 (1898).
16. Kroemer, P. Die Lymphorgane der weiblichen Genitale und ihre Veranderungen bei malignen Erkrankungen des Uterus, Arch. Gyndk. 69, 355-409 (1903). 17. Kundrat, R. Uber die Ausbreitung des Karzinoms im parame-
CANCER
211
tranen Gewebe beim Krebs des Collum uteri, Arch. Gyndk. 69, 355-409 (1903). 18. Brunet, G. Ergebnisse der abdominellen Radikaloperation des Gebihmutterscheidenkrebses mittels Laparotomia hypogestica, Z. Geburtsh. Gym&l. 56, 1 (1905). 19. Langreder, W. Das Parametrium. Funktionelle Anatomie der Ligamentziige sowie ihre Beziehung zur Zervix und Beckenwand besonders wiihrend der Schwangerschaft und Geburt, Thieme, Le-
ipzig (1955). 20. Reiffenstuhl, G. Das Lymphsystem des weiblichen Genitale, Urban & Schwarzenberg, Vienna, pp. 31-34 (1957). 21. Hemiksen, E. The lymphatic spread of carcinoma of the cervix and of the body of the uterus, Amer. J. Obstet. Gynecol. 58, 924 (1949). 22. Holzaepfel, J. H., and Ezell, H. E. Sites of metastases of uterine carcinoma, Amer. J. Obstet. Gynecol. 69, 1027-1036 (1955). 23. Burghardt, E., and Winter, R. Die abdominelle Radikaloperation des Zervixkarzinoms mit pelviner und paraortaler Lymphadenektomie, Film (1987). 24. Piver, M. S. The value of pretherapy paraaortic lymphadenectomy for carcinoma of the cervix uteri, Surg. Gynecol. Obstet. 145, 1718 (1977). 25. Piver, M. S., Barlow, J. J., and Krishnamsetty, R. Five-year survival (NED) in patients with biopsy confirmed aortic node metastasis from cervical carcinoma, Amer. J. Obstet. Gynecol. 139,474478 (1981). 26. Welander, C. E., Pierce, V. K., Nori, D., Hilaris, B. S., Kosloff, C., Clark, D. G., Jones, W. B., Kim, W. S., and Lewis, J. L., Jr. Pretreatment laparotomy in carcinoma of the cervix, Gynecol. Oncol. 12, 336-347 (1981).