- Email: [email protected]
Ovarian carcinoma
Volume 95 Nombeu 3
Panel
diagnosis must still depend upon a curettage. With respec.t to treatment almost all agree that total hysterectomy including the removal of a vaginal cuff of several centimeters and bilateral salpingo-oophorectomy should be performed wherever possible. Some advocate preand others postoperative operative radiation, radiation and still others, a mixture of these methods. Very few advocate radiation alone nowadays, even our Scandinavian colleagues, though figures culled from the Annual Report (thirteenth edition) and from the literature show very little difference in the results obtained by these various methods. It is possible, though not proved I believe that radiation of the vaginal vault either pre- or postoperatively may decrease slightly the incidence of vault recurrence. The results are shown in Tables III and IV and are relatively good for the cervix and ovary, since well over half of all patients seen remain free of the disease for more than 5 years. Figures regarding the incidence of regional node involvement vary widely, from 6 to 28
III.
cancer
Results
of
treatment
of endometrial
(1948-1957)” Apparent 5 year Primary treatment
Predominantly radiation Exclusively radiation Predominantly wsryt Preoperative radiation + surgery ‘Figures were June, tone clinic, surgery
Table
All cases treated
No. of survivors
rf2COVfTy
3,025
2,031
60.5
2,687
1,533
57.6
5,161
3,257
63.1
2,421
1,480
61.1
rate
1965. only.
IV. The
treatment 38 clinics,
Primary
5 and 10 year results of of endometrial cancer (1948-1957)8,119 cases of Stage I, Group 1
treatment
Predominantly radiation Exclusively radiation Predominantly surgery* Preoperative radiation + sumerv ‘One clinic, surgery only.
) :ig+:
~‘z!+iiz: 81
70.3
77.1 74.1 74.5
51.6 58.7 60.2
geriatric
gynecology
359
per cent (Javert, 28 per cent, Meigs, 23 per cent; Townsend, 20 per cent; Winterton, 6 per cent; Brunschwig, 19 per cent), but the incidence in Stage I cases probably does not exceed 3 per cent. In any event, radical operation, including excision of the pelvic nodes, has not proved to be popular and probably kills more women than it saves. Certain other considerations affecting prognosis are well known and will merely be mentioned, such as the degree of differentiation of the growth, the size of the uterus and the depth of invasion of the uterine wall. A well-differentiated superficial growth in an unenlarged uterus is, as might be expected associated with an excellent prognosis; some 90 to 95 per cent of patients with such growths can expect to be cured.
Ovarian DANIEL
Table
on
Los
Angeles,
carcinoma G.
MORTON,
M.D
California
CARCINOMA o F the ovary is the third most common of the malignancies of the female genitals. It is a deadly disease unless discovered accidentally at an early stage and removed. The over-all 5 year survival rates reported in the last 5 years varied from 18 to 37 per cent (see later). It is an interesting disease because it encompasses such a wide variety of tumors which behave in such a wide variety of ways. Most ovarian cancers proceed inexorably to death, sometimes over a prolonged period of time, while others grow slowly from the beginning, undergo spontaneous regression, or respond remarkably well to radiation and/or chemotherapy. One of the most discouraging features of the disease is our inability to develop a means of detecting it at an early stage while it is still curable. The incidence has been given in various ways, as shown in Table I. The age range is from childhood to old age, but the highest incidence falls between 55 and 65 years, thus making ovarian cancer especially important in geriatric gynecology. The symptoms appear late and are often obscure (Table II). The physical findings may point to the likelihood of cancer in which event the growth is
360
Table
Panel on geriatric
I. Incidence
gynecology
of ovarian
cancer
Parsons and Sommers 1 in 100 Randall, on routine pelvic examination 1 in 10,000 Literature-after 3 in 1,000 age 45 8- 15 % of genital malignancies 15% of all ovarian neoplasms
Table
II. Symptoms
of ovarian
cancer
I I Range f%)
Abdominal pain (literature) Abdominal swelling (literature) Abdominal mass (literature) Mass or swelling (D. G. M.) Abnormal bleeding (literature) None (D. G. M.) Averase
duration-8.5
31-61 27-56 1o-45 8-23
Mean f%)
40 40 52 13 8.7
months
usually advanced and incurable. Such features as ascites, bilaterality, nodularity, and papillarity, and fixation are very suggestive indeed. In our clinics, 18.8 per cent were thought to have pelvic masses which were diagnostic, 50 per cent were thought to have suspicious masses, and 26 per cent had ascites. The finding suggested something else entirely in 20 per cent of the cases. Indeed, one may miss the diagnosis until the abdomen has been opened or the patient has been autopsied. This occurred in 11 of 69 of our cases analyzed a few years ago. Since symptoms appear late and abdominal and pelvic findings are uncertain at best the diagnosis is usually made only after the carcinoma exists in an advanced state. Adjunctive diagnostic measures are cytologic examination of vaginal smears and of ascitic fluid and peritoneal washings, culdoscopic examination, exploratory laparotomy, and periodic pelvic examination. Final positive diagnosis depends upon the operative findings and upon histologic examination of a biopsy specimen or of the removed tumor. Cancer cells have been identified in vaginal smears of patients with ovarian cancer but this does not occur frequently enough to be of any practical importance. In the occasional case in which this occurs it permits identification of the nature of an adnexal mass which would otherwise not be possible preoperatively. Cul-de-sac aspiration in selected cases may lead to the correct diagnosis of cancer of the ovary occasionally but is of little or no value as a screening procedure. The Grahams are making
an extensive study of this measure, 1 understand, and have reported a number of instances in which the diagnosis was made in this manner. Keettel also tried this technique and gave it up after negative findings in some 200 odd cases. Abdominal washings at laparotomy may contain cancer cells and thus reveal the malignant nature of an externally smooth, intact ovarian tumor. Keettel reported 5 such cases. On the other hand, he had 4 false positive or suspicious smears in 63 cases of benign cysts and 6 negative smears in 45 cases of ovarian cancer. Culdoscopic examination may occasionally be feasible and lead to a positive diagnosis of ovarian cancer when none was suspected. Finally, exploratory laparotomy because of unexplained pain or adnexal masses may be the only means of arriving at a positive diagnosis. Adherent ovarian tumors, nodular tumors, and ovarian cysts with papillary excrescences are highly suspicious of malignancy. Often the diagnosis is all too obvious, with peritoneal implants, omental metastases, and the like. Finally, of course, positive diagnosis depends upon histologic examination of metastatic masses, or of the tumor itself. From the standpoint of promoting early diagnosis and of prophylaxis in general, we have only periodic pelvic examination and incidental removal of normal ovaries at hysterectomy for uterine disease to consider. In the case of the former, many doubt its value but inevitably such examination occasionally leads to the discovery of pelvic pathology which in turn leads to removal of the ovaries, which is indeed prophylactic though it would be virtually impossible to demonstrate this statistically. In the case of the incidental removal of normal ovaries the same doubt of its value exists, but no one can deny that cancer does occur in left over ovaries and that removal at the time of hysterectomy does prevent this. The prognosis depends upon the histologic findings, as to type and degree of differentiation, upon whether the tumors are freely movable and upon whether they are unilateral or bilateral. According to the recent literature the incidence of types is as shown in Table III. The results of the treatment of carcinoma of the ovary correlate with the histological types as shown in Table IV. All observers agree that the results are increasingly poor as the tumors become more undifferentiated. On the other hand, at the other end of the scale one sees ovarian tumors which are grossly malignant in the respect that implants on the peritoneum
Volume 95 Number
exist
Panel on geriatric
3
and
yet
histologically
are
very
well
dif-
ferentiated (even benign), which allow the patients to live for prolonged periods of time, even without effective treatment. The reported 5 year survival rate for bilateral ovarian cancers is 25 per cent, versus 40 per cent for unilateral tumors. A smooth capsule, free mobility on a pedicle and the absence of adhesions are favorable. Indeed, few ovarian carcinomas which are clinically diagnosable are curable. The vast majority of cures are in cases in which the carcinoma happened to be discovered in a freely movable externally smooth-walled tumor. The over-all 5 year survival rate for ovarian malignancies, as revealed by the literature of the last 5 years, and by our own cases is as shown in Table V. Treatment. The principal treatment is operative removal of as much as possible, whenever possible. Ordinarily, the desired extent of operation is bilateral salpingo-oophorectomy, total hysterectomy, and omentectomy. Radical operations which include the systematic removal of lymphatic chains are of no avail. On the other hand, it is sometimes impossible to remove completely both ovaries and the uterus, yet it appears to be worthwhile to remove the bulk of the tumors even if the operation is incomplete. Exceptions might be those in which the tumors are so buried that it would be difficult indeed to excavate them, even incompletely. In such cases it is better to do nothing since operative disturbance does little more than hasten the end. Radiation therapy of the abdomen often adds to the survival time in our opinion. Certainly some tumors are sensitive to it. It is especially important for the more undifferentiated growths. I doubt if permanent cure ever results from it however. It is not indicated in elderly women with widespread disease. Radioactive gold or radioactive chromic phosphate solutions have been reported as useful in combating fluid formation in about half of the cases. These techniques are not without risk, however, and some patients have developed obstructions and bowel perforations leading to death. I have just heard Keettel of Iowa report on the use of radioactive gold solution used postoperatively as a therapeutic measure even in Stage I cases; it was his conclusion that this substance had greatly improved his results in these cases. Chemotherapy definitely has a place in sup-
gynecology
361
pressing growth activity and in prolonging life. It is too soon to know whether actual cure can be accomplished. Many different preparations have been and are being tried, intraperitoneally, intramuscularly, intravenously, and by mouth. Our experience has been limited to nitrogen mustard, thio-tepa, and chlorambucil and good palliative results have been obtained in approximately a third of the cases. We have seen no cures, however, chlorambucil by mouth, continued over long periods of time, we feel is especially useful. This dismal picture must be combated by further continued
efforts
to make early diagnoses research for cancerocidal
and with chemical
agents.
Table
III.
carcinoma
Incidence of types from the literature
of
ovarian
Incidence TYPO Papillary serous cystadenocarcinema Solid adenocarcinoma Pseudomucinous cystadenocarcinema Krukenberg Dysgerminoma Malignant teratoma Epidermoid, in dermoid Arrhenoblastoma, etc.
Table type
IV. of
Results
correlated
with
(‘$6)
Mean
1 Range
52
48-75
16 13
5-30 2-37
5 2 1 1 1
3-a 1-3
histologic
tumor Five-year SWviva1 (To) Type
Papillary serous cystadenocarcinema Pseudomucinous cystadenocarcinema Solid adenocarcinoma Granulosa cell ovarian carcinoma Dysgerminoma
Table
V. Five-year
survivals
of
Mean
1 Range
24
19-30
47
39-60
6 70 34
o-13 60-80 20-53
ovarian
malignancies Review
of
13 Series-Last Mean Range UCLA-Harbor
5 Years 28% ia-37% 27.7%
Panel
diagnosis must still depend upon a curettage. With respec.t to treatment almost all agree that total hysterectomy including the removal of a vaginal cuff of several centimeters and bilateral salpingo-oophorectomy should be performed wherever possible. Some advocate preand others postoperative operative radiation, radiation and still others, a mixture of these methods. Very few advocate radiation alone nowadays, even our Scandinavian colleagues, though figures culled from the Annual Report (thirteenth edition) and from the literature show very little difference in the results obtained by these various methods. It is possible, though not proved I believe that radiation of the vaginal vault either pre- or postoperatively may decrease slightly the incidence of vault recurrence. The results are shown in Tables III and IV and are relatively good for the cervix and ovary, since well over half of all patients seen remain free of the disease for more than 5 years. Figures regarding the incidence of regional node involvement vary widely, from 6 to 28
III.
cancer
Results
of
treatment
of endometrial
(1948-1957)” Apparent 5 year Primary treatment
Predominantly radiation Exclusively radiation Predominantly wsryt Preoperative radiation + surgery ‘Figures were June, tone clinic, surgery
Table
All cases treated
No. of survivors
rf2COVfTy
3,025
2,031
60.5
2,687
1,533
57.6
5,161
3,257
63.1
2,421
1,480
61.1
rate
1965. only.
IV. The
treatment 38 clinics,
Primary
5 and 10 year results of of endometrial cancer (1948-1957)8,119 cases of Stage I, Group 1
treatment
Predominantly radiation Exclusively radiation Predominantly surgery* Preoperative radiation + sumerv ‘One clinic, surgery only.
) :ig+:
~‘z!+iiz: 81
70.3
77.1 74.1 74.5
51.6 58.7 60.2
geriatric
gynecology
359
per cent (Javert, 28 per cent, Meigs, 23 per cent; Townsend, 20 per cent; Winterton, 6 per cent; Brunschwig, 19 per cent), but the incidence in Stage I cases probably does not exceed 3 per cent. In any event, radical operation, including excision of the pelvic nodes, has not proved to be popular and probably kills more women than it saves. Certain other considerations affecting prognosis are well known and will merely be mentioned, such as the degree of differentiation of the growth, the size of the uterus and the depth of invasion of the uterine wall. A well-differentiated superficial growth in an unenlarged uterus is, as might be expected associated with an excellent prognosis; some 90 to 95 per cent of patients with such growths can expect to be cured.
Ovarian DANIEL
Table
on
Los
Angeles,
carcinoma G.
MORTON,
M.D
California
CARCINOMA o F the ovary is the third most common of the malignancies of the female genitals. It is a deadly disease unless discovered accidentally at an early stage and removed. The over-all 5 year survival rates reported in the last 5 years varied from 18 to 37 per cent (see later). It is an interesting disease because it encompasses such a wide variety of tumors which behave in such a wide variety of ways. Most ovarian cancers proceed inexorably to death, sometimes over a prolonged period of time, while others grow slowly from the beginning, undergo spontaneous regression, or respond remarkably well to radiation and/or chemotherapy. One of the most discouraging features of the disease is our inability to develop a means of detecting it at an early stage while it is still curable. The incidence has been given in various ways, as shown in Table I. The age range is from childhood to old age, but the highest incidence falls between 55 and 65 years, thus making ovarian cancer especially important in geriatric gynecology. The symptoms appear late and are often obscure (Table II). The physical findings may point to the likelihood of cancer in which event the growth is
360
Table
Panel on geriatric
I. Incidence
gynecology
of ovarian
cancer
Parsons and Sommers 1 in 100 Randall, on routine pelvic examination 1 in 10,000 Literature-after 3 in 1,000 age 45 8- 15 % of genital malignancies 15% of all ovarian neoplasms
Table
II. Symptoms
of ovarian
cancer
I I Range f%)
Abdominal pain (literature) Abdominal swelling (literature) Abdominal mass (literature) Mass or swelling (D. G. M.) Abnormal bleeding (literature) None (D. G. M.) Averase
duration-8.5
31-61 27-56 1o-45 8-23
Mean f%)
40 40 52 13 8.7
months
usually advanced and incurable. Such features as ascites, bilaterality, nodularity, and papillarity, and fixation are very suggestive indeed. In our clinics, 18.8 per cent were thought to have pelvic masses which were diagnostic, 50 per cent were thought to have suspicious masses, and 26 per cent had ascites. The finding suggested something else entirely in 20 per cent of the cases. Indeed, one may miss the diagnosis until the abdomen has been opened or the patient has been autopsied. This occurred in 11 of 69 of our cases analyzed a few years ago. Since symptoms appear late and abdominal and pelvic findings are uncertain at best the diagnosis is usually made only after the carcinoma exists in an advanced state. Adjunctive diagnostic measures are cytologic examination of vaginal smears and of ascitic fluid and peritoneal washings, culdoscopic examination, exploratory laparotomy, and periodic pelvic examination. Final positive diagnosis depends upon the operative findings and upon histologic examination of a biopsy specimen or of the removed tumor. Cancer cells have been identified in vaginal smears of patients with ovarian cancer but this does not occur frequently enough to be of any practical importance. In the occasional case in which this occurs it permits identification of the nature of an adnexal mass which would otherwise not be possible preoperatively. Cul-de-sac aspiration in selected cases may lead to the correct diagnosis of cancer of the ovary occasionally but is of little or no value as a screening procedure. The Grahams are making
an extensive study of this measure, 1 understand, and have reported a number of instances in which the diagnosis was made in this manner. Keettel also tried this technique and gave it up after negative findings in some 200 odd cases. Abdominal washings at laparotomy may contain cancer cells and thus reveal the malignant nature of an externally smooth, intact ovarian tumor. Keettel reported 5 such cases. On the other hand, he had 4 false positive or suspicious smears in 63 cases of benign cysts and 6 negative smears in 45 cases of ovarian cancer. Culdoscopic examination may occasionally be feasible and lead to a positive diagnosis of ovarian cancer when none was suspected. Finally, exploratory laparotomy because of unexplained pain or adnexal masses may be the only means of arriving at a positive diagnosis. Adherent ovarian tumors, nodular tumors, and ovarian cysts with papillary excrescences are highly suspicious of malignancy. Often the diagnosis is all too obvious, with peritoneal implants, omental metastases, and the like. Finally, of course, positive diagnosis depends upon histologic examination of metastatic masses, or of the tumor itself. From the standpoint of promoting early diagnosis and of prophylaxis in general, we have only periodic pelvic examination and incidental removal of normal ovaries at hysterectomy for uterine disease to consider. In the case of the former, many doubt its value but inevitably such examination occasionally leads to the discovery of pelvic pathology which in turn leads to removal of the ovaries, which is indeed prophylactic though it would be virtually impossible to demonstrate this statistically. In the case of the incidental removal of normal ovaries the same doubt of its value exists, but no one can deny that cancer does occur in left over ovaries and that removal at the time of hysterectomy does prevent this. The prognosis depends upon the histologic findings, as to type and degree of differentiation, upon whether the tumors are freely movable and upon whether they are unilateral or bilateral. According to the recent literature the incidence of types is as shown in Table III. The results of the treatment of carcinoma of the ovary correlate with the histological types as shown in Table IV. All observers agree that the results are increasingly poor as the tumors become more undifferentiated. On the other hand, at the other end of the scale one sees ovarian tumors which are grossly malignant in the respect that implants on the peritoneum
Volume 95 Number
exist
Panel on geriatric
3
and
yet
histologically
are
very
well
dif-
ferentiated (even benign), which allow the patients to live for prolonged periods of time, even without effective treatment. The reported 5 year survival rate for bilateral ovarian cancers is 25 per cent, versus 40 per cent for unilateral tumors. A smooth capsule, free mobility on a pedicle and the absence of adhesions are favorable. Indeed, few ovarian carcinomas which are clinically diagnosable are curable. The vast majority of cures are in cases in which the carcinoma happened to be discovered in a freely movable externally smooth-walled tumor. The over-all 5 year survival rate for ovarian malignancies, as revealed by the literature of the last 5 years, and by our own cases is as shown in Table V. Treatment. The principal treatment is operative removal of as much as possible, whenever possible. Ordinarily, the desired extent of operation is bilateral salpingo-oophorectomy, total hysterectomy, and omentectomy. Radical operations which include the systematic removal of lymphatic chains are of no avail. On the other hand, it is sometimes impossible to remove completely both ovaries and the uterus, yet it appears to be worthwhile to remove the bulk of the tumors even if the operation is incomplete. Exceptions might be those in which the tumors are so buried that it would be difficult indeed to excavate them, even incompletely. In such cases it is better to do nothing since operative disturbance does little more than hasten the end. Radiation therapy of the abdomen often adds to the survival time in our opinion. Certainly some tumors are sensitive to it. It is especially important for the more undifferentiated growths. I doubt if permanent cure ever results from it however. It is not indicated in elderly women with widespread disease. Radioactive gold or radioactive chromic phosphate solutions have been reported as useful in combating fluid formation in about half of the cases. These techniques are not without risk, however, and some patients have developed obstructions and bowel perforations leading to death. I have just heard Keettel of Iowa report on the use of radioactive gold solution used postoperatively as a therapeutic measure even in Stage I cases; it was his conclusion that this substance had greatly improved his results in these cases. Chemotherapy definitely has a place in sup-
gynecology
361
pressing growth activity and in prolonging life. It is too soon to know whether actual cure can be accomplished. Many different preparations have been and are being tried, intraperitoneally, intramuscularly, intravenously, and by mouth. Our experience has been limited to nitrogen mustard, thio-tepa, and chlorambucil and good palliative results have been obtained in approximately a third of the cases. We have seen no cures, however, chlorambucil by mouth, continued over long periods of time, we feel is especially useful. This dismal picture must be combated by further continued
efforts
to make early diagnoses research for cancerocidal
and with chemical
agents.
Table
III.
carcinoma
Incidence of types from the literature
of
ovarian
Incidence TYPO Papillary serous cystadenocarcinema Solid adenocarcinoma Pseudomucinous cystadenocarcinema Krukenberg Dysgerminoma Malignant teratoma Epidermoid, in dermoid Arrhenoblastoma, etc.
Table type
IV. of
Results
correlated
with
(‘$6)
Mean
1 Range
52
48-75
16 13
5-30 2-37
5 2 1 1 1
3-a 1-3
histologic
tumor Five-year SWviva1 (To) Type
Papillary serous cystadenocarcinema Pseudomucinous cystadenocarcinema Solid adenocarcinoma Granulosa cell ovarian carcinoma Dysgerminoma
Table
V. Five-year
survivals
of
Mean
1 Range
24
19-30
47
39-60
6 70 34
o-13 60-80 20-53
ovarian
malignancies Review
of
13 Series-Last Mean Range UCLA-Harbor
5 Years 28% ia-37% 27.7%