CANCER CELLS IN WOUND WASHINGS IN HEAD AND NECK SURGERY EUGENE BURKE, B.s., AND KUMAO SAKO, M.D.

ANCER of the head and neck region re- C mains localized for presumably long pe- riods of time before metastases appear below the clavicles. Because of these growth char- acteristics, it is felt that a high percentage of patients with this type of cancer should be cured provided the therapy is aggressive.

The major cause of treatment failure in clinically operable cases has been local recur- rent disease. The local recurrence rate for head and neck lesions has been reported to range from 24% to slightly more than 50%.1. 3-5 Multiple foci of recurrence in the region of the operative wound and under the flap area in patients with head and neck cancer has raised the question of the inci- dence and significance of seeding of the wound by cancer cells at the time of opera- tion. Almost all of the malignant intraoral lesions are on the surface and are ulcerated, so that even with careful handling of tissues during surgery, the likelihood of viable tumor cells being left on the operative field is con-

From the Departments of Pathology and Surgery, Roswell Park Memorial Institute, Buffalo, N.Y.

The authors are indebted to Dr. Frank C. Mar- chetta, Chief of Head and Neck A Service; Dr. F. S. Hoheister, Chief of Head and Neck B Service; and Dr. George E. Moore, Director, Roswell Park Memor- ial Institute. for their assistance in initiating and carrying out this study.

Received for publication July 27, 1959.

FIG. 1. Smear showing a large cancer cell from wound washings in a case of carcinoma of the thyroid.

ceivable. The transection of lymphatics with tumor cells in them is also a potential source of seeding.

The problem of contamination of the wounds with cancer cells as a cause of failure of therapy has become of increasing interest recently with the investigation of adjuvant chemotherapy. Unless a significant number of metastases or implantations is directly associ- ated with surgery, the value of local applica- tion of a compound with effective cytolytic action at the time of operation would be minimal.

Smith et al.4 reported 14 positive washings

FIG. 2. Group of 7 malignant cells in wound washings in a case of carcinoma of the pyri- form sinus.

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No. 4 CANCER CELLS IN WOUND WASHINGS IN HEAD & NECK SURGERY Burke d7. Sako 773

TABLE 1 RESULTS OF WOUND WASHINGS IN 261 OPERABLE CASES OF CANCER OF THE

HEAD AND NECK No. pos. No. with

No. for atyp. Site cases ca. cells cells

Larynx 71 5 0 Pharyngeal region 21 1 1 Intraoral* 116 2 3 Maxillary antrum 11 4 0 Nml? 4 0 0 Salivary glands Lip Thyroid 13 1 0 Skin 4 0 0 Neck (unknown Drim.) 4 0 0

0 0

7 0 7 0

Salivary glands 7 0 0 Lip 7 0 0 Thyroid 13 1 0 Skin 4 0 0 Neck (unknown Drim.) 4 0 0

0 1 ,

Neck (prim.) 2 1 Eye 1 0 0 - - -

TOTAL 261 14 4

*The intraoral lesions were situated in the tongue, tonsil, floor of mouth, retromolar area, alveolar ridge, buccal mucosa, and palate.

in 58 head and neck wounds in their series of operative wound washings.

The following study of operative wound washings was done to investigate contamina- tion of the operative wound with tumor cells as a cause for treatment failure.

MATERIAL AND METHODS

Wound washings from 294 patients from Head and Neck services A and B were studied over the 3-year period 1956 through 1958. Of this number, 261 patients had primary clini- cally operable malignant tumors with and without regional metastases and extension. The usual radical procedures were used in operating upon the patients. Wound washings from 33 patients with benign tumors were also studied.

Wound washings were obtained just prior to closure of the skin flaps. All the raw areas were irrigated with 50 to 200 cc. of physiologi- cal saline, and the washings were collected in a basin and sent directly to the laboratory in a glass container. Because of immediate proc- essing, the addition of a fixative was deemed unnecessary.

The washings were centrifuged for 15 min- utes at 2,000 r.p.m. The supernatant fluid was aspirated, and 2 smears were made from the buffy coat. When more than 50 cc. of washings was received, the entire amount was centrifuged in a series of 50-cc. tubes, and 2 slides were made from the material in each tube. In addition, in most cases, a direct

smear was made from the wound mid-way during the surgical procedure and again at the end.

The processing was by the standard Papani- colaou technique, with the smears being fixed immediately in a solution of equal parts of 95% alcohol and ether. After 30 minutes, the smears were stained in Harris’s hematoxylin, OG-6, and EA-36.

There were positive washings from 14 (5.3%) of the 261 malignant lesions and atypi- cal cells from 4. Although the diagnosis made by microscopic study of the tissue was not known to the cytologist at the time, none of the wound washings from the 33 benign lesions was interpreted as containing cells that were either atypical or positive.

The tumor cells were usually found in small groups of from 3 to 5 cells or as single isolated cells (Fig. 1). Some were found that were in the clumps of 7 to 20 cells (Figs. 2 and 3).

COMMENTS

While the percentage of positive slides found is smaller than that reported else- where,4 the technique employed here in head and neck washings was the same as that em- ployed in our chest and peritoneal washings? in which the yield was considerably higher. Using this same technique, Moore et a1.* found that 50y0 of all patients with colon, stomach, and lung cancers had positive peri- toneal washings.

FIG. 3. Clump of tumor cells from a wound washing in a case of carcinoma of the larynx.

774 CANCER July-August 1960 Vol. 13

There appears to be a lack of correlation in our series of positive washings with the us- ual expected number of reported local recur- rences. Interestingly enough, in the report by Smith et al.4 i t was noted that, in their rela- tively short follow-up, local recurrent cancer had not developed in 21 of the 31 patients whose wound washings contained tumor cells, and they raised the question of lack of quanti- tative information available from wound washings. Undoubtedly, the factor of critical colony size cannot be minimized.

Most of our patients have not been fol- lowed long enough for complete analysis as yet for correlation of the time of appearance of recurrence and of survival. These will be reported at a later date.

Thorough evaluation of the efficacy of

chemotherapeutic wound irrigants is as yet forthcoming. However, from our findings at this time, it would appear that other factors may play a more significant role in the inci- dence of local recurrence in head and neck lesions.

SUMMARY 1. Cancer cells were found in wound wash-

ings in 14 of 261 radical operative procedures in head and neck cancers. There were 4 cases in which atypical cells were seen. No false positive or suspicious cells were found in washings from 33 additional benign lesions.

2. The incidence of positive cells in wound washings fell far below the expected incidence of 240/, to 50% local recurrence in head and neck lesions.

REFERENCES

1. HARROLD, C. C.: Present-day methods of surgical treatment of intraoral cancer. In Proceedings of the Second National Cancer Conference. New York, N.Y. American Cancer Society, Inc. 1954; pp. 444-455.

2. MOORE, G. E.; SANDBERG, A. A.; BURKE, E. M.: JOHNSON, R. T., and KATZ, A. D.: Tumor cells in blood and body cavity associated with malignancy of lung and gastrointestinal tract. S. Forum 8: 152-157, 1957.

3. MOORE, 0. S.: Surgical failures in cancer of extrinsic larynx, pharyngeal wall, and base of tongue.

In Proceedings of the Third National Cancer Con- ference. Philadelphia, Pa. J. B. Lippincott Company.

4. SMITH, R. R.; THOMAS, L. B., and HILBERG, A. W . : Cancer cell contamination of operative wounds. Cancer 11: 53-62, 1958.

5. WILKINS, S. A., JR.: Evaluation of surgical failures in treatment of cancer of gingiva. In Proceedings of the Third National Cancer Conference. Philadel hia, Pa. J. B. Lippincott Company. 1957; pp. 562-5Sr.

1957; pp. 559-561.