W.H. ReMine: Palliation for Incurable Gastric Cancer 727

have had control of their disease for a period of time, and the remainder have progessed more slow- ly. Localized disease should be considered for treatment with radiotherapy following hepatic ar- tery infusion. All patients who demonstrate any re- sponse to chemotherapy should be considered for weekly 5-FU in a dose of 15 mg/kg.

Perhaps the most important aspect of chemother- apy involves weekly examinations of the patient, as a result of which we understand the progress of the disease and its complications and manage them more effectively. Most patients die of complications of the cancer, rather than from the cancer itself.

Invited Commentary

Walter Lawrence, Jr., M.D.

Division of Surgical Oncology and Cancer Center, Medical College of Virginia, Richmond, Virginia, U.S.A.

A decision regarding the type of operation most beneficial for any patient with abdominal cancer found to be "incurable" at the time of exploration is always difficult, particularly in patients with gastric cancer. ReMine's presentation of the recent Mayo Clinic experience with operative palliation of gas- tric lesions again demonstrates our inability to pro- vide significant relief to many patients with lesions found to be unsuitable for "curative" resection. This is a frequent problem in that only 1/3 of the patients with gastric cancer undergoing exploration have operative findings that allow resection of all gross disease, and the other 2/3 have liver metasta- sis, peritoneal metastases, lymphatic spread be- yond the limits of a radical gastrectomy, or unre- sectable invasion of adjacent organs and structures. For this group, the surgeon must develop guidelines for selecting the operative procedure most likely to produce some benefit during the life that remains. The choices range from biopsy alone to palliative (or incomplete) resection, and mortality, morbidity, and potential benefit must all be taken into consid- eration. The decision depends on both the results of the various procedures that are technically feasible and the potential for subsequent nonoperative treat- ment. The last statement in this excellent paper is that this choice must not be made casually, and I could not agree more.

ReMine has done a careful retrospective review of the results of the various surgical options that are available when a gastric cancer is determined to be incurable. The assessment of these options is admit- tedly imprecise since the choice of resection, as op- posed to bypass or "os tomy" operations, is not

available as frequently with the more advanced le- sions. Any retrospective comparison of results of palliative resection and gastrojejunostomy, gastros- tomy, or jejunostomy might tend to favor resection since this approach might be chosen for less ad- vanced disease in many instances. The questions the surgeon must answer in dealing with this prob- lem are:

1. If both palliative resection and bypass opera- tions are feasible in a given patient, is it worthwhile to carry out the more extensive procedure (resec- tion)?

2. If resection is not feasible without resorting to total gastrectomy, is a resection of this extent truly palliative?

3. If resection is not feasible, is bypass gas- troenterostomy, gastrostomy, or jejunostomy bene- ficial for the patient with gastric cancer and, if so, under what circumstances?

ReMine's conclusions from this study are that gastroenterostomy is probably worthwhile if distal obstruction is present, that the results of palliative partial resection are only slightly better than those following gastroenterostomy although survival time is prolonged, and that total gastrectomy is generally too extensive a procedure for palliation. He also concludes that prosthetic tubes, gastrostomy, and jejunostomy all fail to achieve the desired palliative benefits except in situations where these approach- es replaced long-term intravenous therapy and al- lowed discharge of the patient from the hospital. These are pessimistic, but realistic, conclusions based on an extensive experience in a major medi- cal center. In his discussion of the philosophy of palliative surgery, ReMine stresses the need for op- erative and histologic confirmation of the pre- operative clinical findings that appear to indicate in- curability. This supports the need for operative ex- ploration of most patients with gastric cancer, since few are clearly "incurable" on the basis of physical examination. I agree that most patients with gastric cancer should be carefully explored to determine whether or not a "curative" resection is actually feasible.

Our own experience reported from the Memorial Hospital some years ago [1] was similar in many re- spects to Ihese recent data from the Mayo Clinic, but the differences between reports are worth not- ing. We attempted to compare palliative gastric re- section with gastrojejunostomy, gastrostomy, and jejunostomy in terms of both relief of symptoms and survival time, despite the fact that the groups of pa- tients undergoing these various procedures were not truly comparable. Nevertheless, the observed results of distal gastric resection in this series were beneficial enough to favor this choice after review of our data, since symptom relief was so rarely

728 World J. Surg. Vol. 3, No. 6, 1979

Table 1. Evaluation of relief of symptoms after noncurative subtotal gastrectomy, 1941-1955 [1].

Number %

Operative survivors Data adequate for evaluation Degree of palliation obtained:

Good (relief of symptoms > 6 mo) Fair (relief of symptoms 3-6 mo) Limited

(relief of symptoms < 3 mo) No palliation

67 57 100

18 31.6 / 14 24.6/56"1

12 21.1 l 13 22.8/43"9

achieved with any other procedure. The majority of patients undergoing palliative subtotal gastrectomy had relief of symptoms for more than 3 months and almost 1/3 had symptom relief for more than 6 months (Table 1). In contrast, none of our 86 pa- tients with bypass operations had satisfactory relief of symptoms of obstruction, bleeding, or other di- gestive complaints for as long as 3 months following operation. Patients undergoing palliative total gas- t rectomy in our series had a high mortality rate, sig- nificant morbidity, and rarely adjusted to their post- operative physiologic problems and symptoms soon enough to consider the palliation as beneficial as that observed in the partial gastrectomy group. Our conclusions regarding the role of total gastrectomy for palliation (41 patients) were similar to those of ReMine, but a few patients obtained significant ben- efit, particularly when obstruction was a major problem and there was a limited amount of residual disease after palliative resection.

Although the duration of life after all attempts at surgical palliation was short, survival time must be considered a factor in the decision process. Our data on mean survival time after these various oper- ative procedures (Table 2) demonstrate a survival advantage for patients whose lesions were resected. It is impossible to determine the effect of the extent of disease found at exploration on the choice of op- eration so that these data are less convincing than those relating to symptom relief.

Another consideration in the choice of palliative procedure might be the cause of incurability. It can be seen in Table 3 that unresectable local invasion of other organs was associated with a longer surviv- al time after palliative gast rectomy than other causes of unresectability, while patients with liver metastases had a lower incidence of significant symptomatic benefit than the other groups (Table 4). In patients in whom the choice of palliative re- section is felt to be a "margina l" decision, observa- tions of this kind might assist the surgeon.

Returning to the 3 questions posed at the begin- ning of this commentary , my opinion in response to the first quest ion is that resection should probably be carried out instead of a bypass operation for pal- liation if both procedures are technically feasible. My response to the question regarding palliative to- tal gast rectomy is similar to that of ReMine, but this procedure should not be ruled out as an alternative in every circumstance, since a patient in good gen- eral condition with limited residual disease may benefit from palliative total gastrectomy if there were significant obstructive symptoms prior to operation. The third question, regarding the advisability of some form of bypass operation when resection is not feasible, is the most difficult one to answer. Generally, bypass procedures utilizing external tubes (gastrostomy or je junostomy) produced no relief of symptoms and added considerable com- plications in our experience. They are justifi-

Table 2. Duration of life after noncurative operations, 1941-1955 (operative deaths excluded) [1].

Mean survival Number (months)

Laparotomy only 239 4.6 Bypass operations 86 4.2

Gastrostomy 32 6.9 Jejunostomy 27 3.3 Gastroenterostomy 27 3.9

Palliative resection 108 9.0 Subtotal 67 9.5 Total 41 8.2

Table 3. Anatomic reasons for incurability in patients with noncurative subtotal gastrectomy, 1941-1955 [1].

Number %

Mean survival (months)

All patients 67* 100.0 9.5 Liver metastases 17 22.4 7.2 Peritoneal metastases 18 23.7 7.5 Nonresectable lymphatic

spread 34 44.7 10.0 Other organs invaded 7 9.2 17.9

*in 9 instances, 2 reasons for incurability were found.

W.H. ReMine: Palliation for Incurable Gastric Cancer 729

Table 4. Anatomic reasons for incurability and relief of symptoms by noncurative subtotal gastrectomy, 1941- 1955 El].

Symptom relief > 3 months

Total number Number %

All patients 57* 32 56 Liver metastases 12 4 33 Peritoneal metastases 14 9 64 Nonresectablelymphatic spread 30 16 53 Other organs invaded 7 6 86

*Number with adequate data (see Table 1).

able in the rare instance when the patient's gen- eral condition is such that a reasonable survival time is expected, but prolonged intravenous sup- port in the hospital would be required. In this rela- tively uncommon circumstance, gastrostomy or je- junostomy may allow the patient to return home for his or her remaining months, but most patients with advanced gastric cancer are not candidates for these ineffective procedures. We also avoid gas- troenterostomy as a palliative procedure in patients unsuitable for palliative resection unless complete or near-complete distal obstruction is present, since the gains are minimal.

All of ReMine's comments and my comments have focused on the operative decisions as if this were the only palliative therapy we have to offer. Radiation therapy is ineffective as a palliative treat- ment for gastric cancer in most instances, since dis- ease in patients found unsuitable for resection is not localized enough to undergo such regional treat- ment. On the other hand, radiation therapy has been useful in relieving localized areas of obstruc- tion, particularly in the region of the cardia, and pa- tients with chronically bleeding gastric cancers have also benefitted from radiation. However, the nature of the pattern of spread of gastric cancer in the patient who is not amenable to operative thera- py usually makes systemic chemotherapy seem more appropriate than radiation therapy.

Many chemotherapeutic agents have been used as single agents, but generally the results have been disappointing. The antimetabolite, 5-fluorouracil (5- FU), was the most frequently employed of these agents until combination drug regimens were devel- oped. In one large review [2], approximately 22% of patients treated with 5-FU demonstrated transient evidence of improvement of a limited degree, with no definite increase in survival time. There is more enthusiasm, however, for various combinations of agents for patients with advanced gastric cancer. In current prospective, clinical trials, these combina- tions appear to produce somewhat higher rates of objective response than the single agents. Agents in these combinations include 5-FU, nitrosoureas, mytomycin C, and adriamycin in various combina- tions [3]. The combination of 5-FU, adriamycin, and mytomycin C (FAM) has been associated with a 50% objective response rate in a recent trial [4]. It is to be hoped that these investigations will yield better response rates for palliation than those ob- served in the past with single agents.

Webster's Dictionary defines "palliate" as " to mitigate, lessen, or abate." It is quite clear that the operative alternatives for incurable gastric cancer patients are limited, and that they often fail to achieve palliation in these terms. On the other hand, improved chemotherapy programs may well prove to be of benefit, and palliative resection or palliative procedures to relieve obstruction may fa- cilitate chemotherapy.

References

1. Lawrence, W., Jr., McNeer, G.: The effectiveness of surgery for palliation of incurable gastric cancer. Can- cer 11:28, 1958

2. Comis, R.L., Carter, S.K.: A review of chemotherapy in gastric cancer. Cancer 34:1576, 1974

3. Moertel, C.G., Mittelman, J.A., Bakemeier, R.F., Engstrom, P., Hanley, J.: Sequential and combination chemotherapy of advanced gastric cancer. Cancer 38:678, 1976

4. MacDonald, J.S., Wooley, P.V., Smythe, T., et al: 5- Fluorouracil, adriamycin and mitomycin-C (FAM) combination chemotherapy in the treatment of ad- vanced gastric cancer. Cancer (in press)