M of initial surgical treatment of cancer of

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1 ATTEMPTED PALLIATION BY RADICAL SURGERY FOR PELVIC AND ABDOMINAL CARCINOMATOSIS PRIMARY IN THE OVARIES ALEXAXDER BRUNSCHWIG, M.D. UCH HAS been written about the results M of initial surgical treatment of cancer of the ovary, and the reported over-all 5-year salvage rate varies between 25 and 30%. But patients who, after operation, have recurrences in the form of pelvic and abdominal metastases or who are first seen in this advanced stage of the disease present an incurable situation. By way of documentation, little or nothing has been written on what, if anything, may be accomplished by palliative attempts with surgical therapy. Such palliative attempts constitute measures for the temporary relief of the mechanical symptoms that are produced in the advanced stages of this disease. Large masses in the abdomen contribute to general discomfort and may be the source of local pain. Heavily infiltrated omentum not only constitutes a large mass but also is a source of much of the ascites usually presented by these patients. Of special importance is the factor of intestinal obstruction almost always present in some degree and involving one or several areas in the large or small bowel or both. This obstruction is not similar to that resulting from intrinsic bowel lesions but takes the form of what the writer refers to as carcinomatosis ileus. The segments of bowel wall are infiltrated with neoplasm, are thickened, and peristalsis is thus much reduced or hardly present. In addition, corresponding portions of mesentery are also heavily infiltrated by cancer, and this contributes to the ileus in the segments of bowel. In some instances most of the infiltration is in the mesentery, with relatively little in the walls of the bowel. While the disease is, indeed, in an advanced stage in these patients, their general condition often is not too precarious, and they and their immediate families are usually desirous From Memorial Center for Cancer and Allied Diseases, New York, N.Y. This study was facilitated by a grant from the James S. and Marvelle Adams Foundation. Received for publication April 29, of having anything attempted that will offer some measure of relief and the hope of some prolongation of life. In effect, the problem of palliation of advanced ovarian cancer is one of attempting relief of chronic intestinal obstruction due to extrinsic neoplasm, which obstruction will ultimately recur as the patient is finally overwhelmed by cancer. This report summarizes an experience in attempting surgical palliation in a series of patients in the terminal stages of abdominal carcinomatosis that was primary in the ovaries, and in whom either previous laparotomy had been performed, usually elsewhere, with excision of what appeared to be localized disease in one or both ovaries and there was subsequent recurrence or only biopsy was done at laparotomy because the disease was already widespread. Almost all had received radiation therapy in various forms (such as X ray or radioactive gold instillations) and some had had chemotherapy. The patients were all operated upon by the writer; thus, such factors as individual judgment and manner of procedure were, in a sense, controlled. The objectives in each case were to resect as much tumor tissue as possible with safety, to resect heavily infiltrated omentum, to excise larger metastatic masses on the peritoneal surfaces, to excise the most heavily infiltrated segments of bowel that appeared to be the sites of most of the carcinomatosis ileus (obstruction), or to perform anastomotic bypasses when large masses of involved bowel could not be excised. In this way it was hoped to temporarily reduce the severity of symptoms, permit greater benefit from ingested food, and possibly prolong life. For obvious reasons, all tumor tissue was not excised, and it was a foregone conclusion that any amelioration of symptoms would be entirely temporary. All patients considered had been operated upon 5 or more years previously. Because each patient presented an individual situation, no 2 operations were aiike but they may be grouped to some extent, as follows: 384

2 No. 2 SURGICAL PALLIATION IN OVARIAN CARCINOMATOSIS * Brunschwig 385 Excision of markedly inuolued omentum with or without resection of peritoneal and mesenteric implants. There were 4 patients in this group including 1 who was 17 years of age. One surgical mortality due to peritonitis occurred on the third day after operation. The other patients survived 2, 4, and 29 months respectively. Resection of omentum heavily infiltrated by cancer and radical panhysterectomy. These patients had received exploratory celiotomy elsewhere and had, in some instances, received radiation therapy. The seven patients in this group survived 2%, 3, 4, 5, 8, 13, and 13 months respectively, averaging 7 months. Resection of one or more segments of small bowel with or without omentectomy and excision of larger peritoneal and mesenteric implants. There were 9 patients in this category. One died on the ninth day and is considered a surgical mortality. Among the remaining 8 patients, survival varied from 1% months to 11 months, averaging 6 months. Resection of an involved segment of sigmoid or descending or transverse colon, with or without resection of omentum, with or without resection of a segment of small bowel, and with or without excision of larger peritoneal implants. There were 24 patients in this group. One died of peritonitis 2 weeks after operation and is regarded as a surgical mortality. Nine survived 2 to 5 months; 5 survived 6 to 11 months; 2 survived 1 year 1 month and 1 year 5 months respectively; 3 survived 1 year 7 months, 1 year 8 months and 1 year 9 months respectively; 1 survived 2 years 11 months; and 3 survived 8 years, 8 years, and 9 years respectively. Among these patients, only 2 received permanent colostomies. The 3 patients surviving 8, 8, and 9 years respectively deserve special comment. Case 1. The patient was 50 years old in htovember, 1949, when laparotomy was performed elsewhere, resulting in the finding of cancer in the right ovary. This was excised. Postoperative X-ray therapy was given and was repeated in August, 1951, because of pain in the back and the presence of a pelvic mass. A second laparotomy was performed in March, 1952, for excision of a left ovarian carcinomatous mass, 8 cm. in diameter. It was adherent to the colon, necessitating resection of a segment of the colon 5 cm. long. A total hysterectomy was also done, together with excision of the omentum in 2 segments-measuring 19 cm. and 30 cm. in greatest diameters respec- tively. Histological study of the endometrial lining was reported as showing superficial endometrial carcinoma. The omentum was negative for metastases. A temporary diverting colostomy was done and later closed. The patient is living and well 8 years after the last operation. Case 2. The patient was 61 years old in October, 1947, when a vaginoabdominal panhysterectomy for left ovarian carcinoma and a vaginectomy for metastasis in the anterior vaginal wall were performed. One month later, a metastatic node was excised from the left groin. Five years later, in 1952, the patient presented evidence of high grade obstruction in the mid-transverse colon resulting from extrinsic pressure. At laparotomy, this was found to be a metastatic mass of ovarian carcinoma in the transverse mesocolon, situated essentially in the zone of attachment to the colon but compressing the latter. Wide resection of mesentery, mass, and transverse colon was performed with end-to-end anastomosis. The patient remains well 8 years after the last operation. Case 3. The patient was 55 years old. In 1948, a malignant ovarian cyst was excised and a supracervical hysterectomy was performed. Postoperative X-ray therapy was given elsewhere. In 1951, celiotomy was again performed for excision of a large mass of recurrent ovarian carcinoma in the cervical stump. The latter was excised together with a segment of pelvic colon infiltrated by the neoplasm, and end-to-end anastomosis was performed. In June, 1957, and also in February, 1958, repairs of incisional hernias were carried out, affording the opportunity to observe that no further metastases were present. The patient is living and well 9 years after excision of the recurrent ovarian carcinoma. The good results in these patients were achieved, of course, in the absence of generalized spread of the disease throughout the abdomen, but the point emphasized is that these were instances of ovarian carcinoma recurrent after definitive previous treatment, and they gave the clinical picture of widely disseminated cancer in the pelvis and abdomen. Right colectomy, with or without omentectomy and with or without resection of larger peritoneal metastases or other segments of bowel (Fig. I). In these patients, the spread of carcinoma was such as to seriously compromise the functions of the lower small bowel and the right colon. The fact that a right

3 386 CANCER March-April 1961 Vol. 14 FIG. 1. Surgical specimen from a patient who had extensive resections for advanced metastatic ovarian cancer, as described in text. The letters indicate the following: R, right colon showing points of obstruction (1 and 2) due to cancer: I, lower ileum: 0, omentum with metastases; U, uterus and adnexa with primary tumor (P) in the right ovary: and C, a segment of the pelvic colon adherent to the posterior aspect of the uterus by metastases. colectomy was necessary to resect the major portion of the intestinal involvement is evidence of the extent of disease, all of which, of course, was not removed. There were 11 patients in this group, 1 of whom died on the eighth postoperative day and is considered a surgical mortality. Survivals ranged from 1 to 11 months, with an average of a little more than 3 months. Very major resections. There was such variation in each case in this group that they are summarized individually as follows: Case 4. The patient had a partial hepatectomy, with right lobe and retroperitoneal node excision. She survived for 2 months after the operation. Case 5. The patient had a left hepatic lobectomy, with a partial pancreatectomy and excision of a segment of the abdominal wall in the left upper quadrant. She died of shock and hemorrhage shortly after the operation. Case 6. The operation for this patient consisted of excision of a large mass of recurrent ovarian carcinoma. She survived for 8% months after the operation. Case 7. The patient had a total gastrectomy, resection of the body of the pancreas and a right colectomy. She survived for 2 days and then died of shock. Case 8. The patient had an excision of a mass adherent to the undersurface of the leet diaphragm, partial gastrectomy and excision of major portion of transverse colon. She survived for 8% months. Case 9. The patient had an extensive retroperitoneal lymph node resection. She died of shock in 2 days. Case 10. The patient had a gastroenterostomy to circumvent pyloric and duodenal obstruction resulting from metastatic ovarian carcinoma. She survived for 2 years. Case 11. The patient had a supravaginal hysterectomy and salpingo-oophorectomy; 17 months later, she had a ileotransverse colostomy, and 5 months after this there was a resection of a segment of the small bowel and a segment of the right transverse colon. She survived for 1 year 10 months after the first operation. Case 12. The patient had a resection of a mass of recurrent carcinoma of the right ovary 2 years after previous panhysterectomy and extensive radiation for ovarian carcinoma. Clinically, the bladder appeared to be involved and the right ureter obstructed. The

4 I No. 2 SURGICAL PALLIATION IN OVARIAN CARCINOMATOSIS - Brunschwig 387 vagina and the recurrence were resected. The bladder was preserved, and the right ureteral obstruction was released. The patient is living and well after 10 years. Case 13. The patient was 54 years old in 1944, when a right oophorectomy for carcinoma of the right ovary was performed. A subtotal hysterectomy for carcinoma of the left ovary was performed in She received million volt roentgen therapy for a pelvic recurrence in 1953, and a total pelvic exenteration for persistent neoplasm in the pelvis that was invading the bladder, rectum, and vagina was done in She died of uremia in December, 1959,5 years 3 months after exenteration, and no evidence of recurrent or metastatic cancer was found. Thus, in this group, there were 3 instances of surgical mortality, 1 patient survived 2 months, 2 survived a little more than 8 months, 1 lived 1 year 10 months, 1 lived 2 years, 1 survived 5 years 3 months and died of uremia with no frank evidence of recurring disease, and 1 is living and well 10 years after operation. DISCUSSION Clinicians who have observed numbers of patients with ovarian cancer for an appreciable period of time usually can recall isolated instances in which survival has been unusually long with or without radiation therapy. These are exceptional instances and are not sufficiently common to assume such survivals will obtain with any degree of certainty in any one case if nothing further is done. This occurrence, however, is striking and has given rise to an impression that such instances are more common than they really are. Moreover, in a number of such instances, original biopsy diagnosis is sometimes lacking. Ovarian cancer is one of the most unpredictable forms of neoplastic disease in its evaluation, especially if mechanical interference with gastrointestinal tract function does not occur early. Evaluation of attempts at palliation as described are, indeed, difficult. There were 65 patients in this very heterogeneous series. The surgical mortality rate, defined as death within 30 days of operation, consisted of 7 patients, an incidence of 11%. Three of the postoperative deaths were in patients who, of necessity, had very radical upper abdominal excisional procedures involving partial hepatectomy, partial gastrec- tomy, and partial pancreatectomy. Excluding these, the surgical mortality rate was 4 of 62 patients or 6%. Among the postoperative survivors in the entire series, 1 is living after 10 years, 1 is living after 9 years, and 2 are living after 8 years, free of disease; 1 died of uremia after 5 years -about 8% cures ; 3 lived approximately 2 to 3 years; and 8 lived 1 year to 1 year 5 months. In the 5 survivors of 10, 9, 8 (2 cases) and more than 5 years respectively, the disease, although recurrent after previous treatment, had metastasized only locally and was maa-oscopically entirely resectable. This localized involvement, however, was not appreciated until celiotomy had been performed. Except for the 5 cured patients, gross disease was left behind in all instances. The patients, therefore, were not completely re- Iieved of all symptoms, but immediate relief was often achieved, not only objectively but subjectively as well. When there was survival for 6 months or more, the writer is of the opinion that the operation was, indeed, justified for palliative purposes. Fifteen patients lived 6 to 11 months, an incidence of about 25%. Thus (again excluding the 5 very long term survivors), 26 patients in the series, or 40%, achieved some palliation as defined by survival of 1, 6 to 11 months (15 patients), 2, 1 to 2 years (8 patients), and 3, 2 to 3 years (3 patients). The results in the entire series are summarized in Table 1. The timeworn argument that needless surgery is performed when the lifespan of the patient must obviously be brief and that such patients should be let die in peace is not subscribed to by the writer. Usually, patients with progressing advanced malignant disease do not die in peace. Obviously, judgment must be exercised in TABLE 1 SIJRVIVAI, RATES FOR 65 PATIENTS OPERATED UPON FOR ADVANCED ClRCINOMATOSIS OF THE ABDOMEN PRIMARY IN THE OVARIES Survival time Surg. mort.* 1+ to 5 mo. 6 to 11 mo. 1 to 2 yr. 2 to 3 yr. 5 to 10 yr. TOTAL *See text for definition. No. pt % Pt

5 388 CANCER March-April 1961 Vol. 14 performing radical excisional surgery in these patients. Debilitated and/or elderly individuals with cancer spread beyond the abdomen or with advanced disease that is not causing, at the moment, particularly acute and distressing symptoms are not subjects for operation. Operation is considered only when symptoms (gastrointestinal disturbances) are severe enough to warrant an attempt at immediate relief. SUMMARY AND CONCLUSIONS Advanced metastatic cancer of the abdomen primary in the ovaries that is recurrent after initial surgery and/or radiation therapy may result in acute or semiacute disturbances of gastrointestinal tract functions, especially obstruction as a result of secondary involvement of the latter ( carcinomatosis ileus ). Such disturbances in function may also arise as a re- sult of the evolution of large and numerous intraperitoneal implants and ascites. Palliation was attempted by excision of portions of the tumor, and omentum, if present, and resection of the more heavily involved segments of large or small bowel. In some 40% of this series, palliation in varying degrees was achieved in my opinion. In the absence of very emphatic contraindications, laparotomy is indicated in selected patients of the type described, because there is always the possibility that the recurrence and/or metastases are localized and macroscopically entirely resectable. Under these circumstances, the chances for prolonged control are possible, as was proved from instances described in this paper in which patients are living and well, free from disease, 8, 8, 9, and 10 years respectively and 1 patient who was a 5-year survivor and died of uremia without recurrent cancer.