Wound infections and recurrence in head and neck cancer ROBERT M. JACKSON, MD. and DALE H. RICE, MD, Los Angeles, California
Recent publications in the general surgery literature have reported improved survival in abdominal cancer surgery in those in whom a postoperative wound infection develops. We reviewed our experience with 100 consecutive patients operated on for head and neck cancer. All patients had 5-year followup. The complete report covers site and stage. In summary, for all cancers of the larynx (N = 60), the recurrence rate was 45% for those In whom a wound infection developed and 26% for those in whom no such infection developed. For cancers of the oral cavity and pharynx (N = 40), the recurrence rate was 80% for those in whom wound infections developed and 51% for those who had no infections. Because of the small number of patients in whom recurrence developed, with or without infection, the relationship does not reach statistical significance. For head and neck cancer, unlike abdominal cancer, the development of a postoperativewound infection may have an adverse effect on survival rather than a SalUtOry effect. [OTOLARYNGOL HEAD NECK SURG 1990;102:331.)
T h e effect of postoperative wound infection on tumor and recurrence has been debated for many years. Improved survival with postoperative infection has been reported with bronchogenic carcinoma, melanoma, and colon cancer. Others, however, have reported no difference in long-term survival in these same turn or^,^.^ although Papachristou and Fortnel-6 did find a decreased local recurrence rate. To our knowledge, there have been no reports devoted to the effect of postoperative wound infection on recurrence in head and neck squamous cell carcinoma. We reviewed our experience with 100 consecutive patients who received surgical treatment of their head and neck cancer. PATIENTS AND METHODS The patient records of 100 consecutive patients diagnosed as having head and neck squamous cell carcinoma were reviewed. Only patients treated with surgery for cure (all except stage I with postoperative radiation therapy) were included. Patients who did not have clear surgical margins (confirmed by the final his~~
From the Department of Otolaryngology-Head and Neck Surgery, University of Southern California School of Medicine, Los Angeles County-University of Southern California Medical Center. Submitted for publication Jan. 17, 1989; revision received Nov. 14, 1989; accepted Nov. 15, 1989. Reprint requests: Dale H. Rice, MD, Department of OtolaryngologyHead and Neck Surgery, University of Southern California School of Medicine, Los Angeles County-University of Southern California Medical Center, Box 795, 1200 North State St., Los Angeles, CA 90033. 23/1/ 18265
Table 1. Relation between stage and recurrence in patients with laryngeal cancer* Stage I
II
111
IV
Total
Developed postoperative - 213 011 215 419 infection (67%) (0%) (40%) (45%) No postoperative 013 2/19 6/20 519 13/51 infection (0%) (10%) (30%) (56%) (26%) *Figures indicate numbers of patients with cancerltotal number of patients (N = 60).
topathologic examination) were omitted from the study. Thus persistent tumor could presumably not account for the infection. Five-year follow-up data were available for all patients. Patients were clinically staged according to the standards set by the American Joint Committee on Cancer in 1980.’ The age range of patients was from 31 to 83 years of age. The average age was 59 years old. There were 75 men and 25 women. All patients had biopsy-proven squamous cell carcinoma before definitive treatment. The most common site of cancer was the larynx. Other sites included were the oral cavity, pharynx, nasal cavity, and maxillary sinus.
RESULTS The 100 patients were divided into two groups according to site. In group 1 were patients with laryngeal cancer; group 2 included patients with cancer of the oral cavity, pharynx, nose, or sinus. Sixty patients had 331
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332
OtolaryngologyHead and Neck Surgery
JACKSON and RICE
Table 2. Relation between stage and recurrence in patients with cancer of the oral cavily, pharynx, nose, or maxillary sinus (N = 40) Stage
Developed postoperative infection No postoperative infection
I
II
111
IV
Total
-
112 (50%) 419 (44%)
1 /1 (100%) 6111 (56%)
212 (100%) 618 (75%)
415 (80%) 18/35 (51yo)
217 (29%)
Table 3. Relation between stage and recurrence in patients with cancer of all sites (N = 100) Stage
Developed postoperative infection No postoperative infection
I
II
111
IV
Total
-
315 (60%) 6/28 (21%)
1I 2 (50%) 12/31 (39%)
4/7 (57%) 11/17 (65%)
8/14 (57%) 31 186 (36%)
2/10 (20%)
Table 4. Relation between micoorganism cultured in postoperative wound infection and cancer recurrence Mlcroorganisrn
Present in patient cultures
Recurrence rate
P. aeruginosa Enterobacter sp. S. aureus Klebsiella sp. S. epidermidis S. viridans Veillonella sp.
5 4 3 3 1 1 1
80% 75% 33% 100% 100% 100% 100%
cancer of the larynx, whereas 40 patients were’ in the mixed site group (the majority of the latter had cancer of the oral cavity or pharynx). Each group was then divided into those in whom a postoperative wound infection developed and those in whom no such infection developed. Recurrence rates were calculated within both groups per individual stage, as well as total patients. All recurrences were at the primary site or in the treated neck. All infections involved the primary site and treated neck. In the first group of patients (laryngeal cancer), the overall recurrence rate of patients in whom a postoperative infection developed was 45%, as compared to 26% for those with no infection (Table 1). Because of the small number of infections, these values are not significant ( p = 0.2). In the second group of patients (Table 2-oral cavity, pharynx, and nose and sinus), the recurrence rates with
vs. without postoperative infection were: stage 11, 50% vs. 44%; stage 111, 100% vs. 56%; and stage IV, 100% vs. 75%. For all patients in this group, the recurrence rates were 80% vs. 5 1%, respectively. No stage I patient experienced a postoperative infection. Thus, both in terms of individual staging, as well as the total percentage of patients, recurrence rates were higher in patients in whom postoperative infection developed. Again, because of the small number of infections, the numbers do not reach significance (Fisher’s exact, p = 0.155). Lastly, for all 100 patients (Table 3), the recurrence rates with vs. without postoperative infection were: stage 11, 60% vs. 21%; stage 111, 50% vs. 39%; and stage IV, 57% vs. 65%. For all patients, the recurrence rates were 57% vs. 36% (Fisher’s exact, p = 0.20). Of the 14 patients in whom wound infection developed (either with or without fistula), culture results were available in 1 1 patients (Table 4). Pseudomonas aeruginosa was present in five, Enterobacter sp. in four, Staphylococcus aureus in three, Klebsiella sp. in three, Staphylococcus epidermidis in one, Streptococcus viridans in one, and Veillonella sp. in one. There was no relationship between a particular microorganism and cancer recurrence, other than a somewhat lower rate with Staphlococcus aureus (33%), as compared to the others (75% to 100%). DISCUSSION
Reports of improved survival of cancer patients in whom postoperative wound infection develops have been published in recent years. Ruckdeschel et al.’ and
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Volume 102 Number 4 April 1990
Wound infections and recurrence in head and neck cancer 333
Sensenig et a1.8 have reported increased survival in patients who had pulmonary resections for bronchogenic carcinoma in whom empyema subsequently developed. However, Cady and Clifftod failed to find any difference in 5-year survival. Interestingly, their study did reveal a higher incidence of streptococcal and staphylococcal infection in the patients who did survive 5 years. Although, our numbers are too small to draw any definitive conclusions, it is notable that infections associated with Staphylococcus aureus did have a lower incidence of recurrence as compared with the other bacteria, which were mostly gram-negative bacilli, and was similar to the group without infection. There were no streptococcal (pyogenes) infections. Herter and Slanetz3 studied patients with colorectal carcinoma. Of 25 anastomotic recurrences, 22 occurred in patients who had been given antibiotic prophylaxis. It was concluded that suppression of colonic flora increased the risk of czncer recurrence. In other words, the normal bacteria acted to deter tumor implantation at the anastomotic site. However, Molin and Riegep found no difference in colorectal cancer recurrence rates between those who had and had not received antibiotic prophylaxis. Pathogenic bacteria were first popularized by Coley and Hoguet’ as anticancer agents more than 70 years ago. They noted that protection was afforded only to local lesions and not to distant metastases. Similarly, Papachristou and Fortner6 found that patients with stage I1 melanoma had lower incidence of local tumor recurrence than occurred in patients in whom postoperative infection developed; however, patient survival and the ultimate course of the disease were not affected. To our knowledge, there have been no previous reports on the effect of postoperative wound infection on head and neck squamous cell carcinoma recurrence rates. We found an overall higher incidence of tumor recurrence in those patients in whom postoperative infection developed, except in stage IV disease, in which the rates were similar. This is unlike most other studies (vide supra), which found no difference or a lesser incidence of recurrence with infection. Our results may reflect that patients with larger tumors-and thus with an inherently poorer prognoses-will need larger resections and thus infection will be more likely to develop. This is seen in our stage IV patients, in whom there is little difference between the infected and noninfected groups. However, in stage I1 lesions there is an appreciably increased recurrence rate in the presence of infection (60%vs. 21% for all sites). Thus, it may be that larger tumors would be less affected by variables such as local infection, but the number of patients with infection is too small to be certain. It is also possible
that streptococcal and staphylococcal infection have a different local tumoricidal effect than gram-negative bacilli, which were the predominant causative agents in the majority of wound infections we studied. CONCLUSION
One hundred patients with squamous cell carcinoma of the head and neck treated for cure with either surgery or combined therapy (surgery and radiation) were reviewed. Recurrence rates were higher for patients with oral cavity, pharynx, nose, or sinus cancer in whom a postoperative infection developed. In patients with laryngeal cancer-although stage I1 patients with postoperative infection had higher recurrence rates-stage 111 and IV patients had lower rates, but the number of patients with infections was small. However, overall the laryngeal cancer patients had higher recurrence rates if postoperative wound infection developed. In all cases, however, the numbers were too small to reach statistical significance. Whether or not this association is causative is unknown, but it does imply that postoperative wound infection may adversely affect the patient with squamous cell carcinoma of the head and neck. Much larger numbers of patients would need to be studied to definitely answer this question.
REFERENCES
1. Ruckdeschel JC, Codish SD, Strauhan A, McKneally MF. Postoperative empyema improves survival in lung cancer: documentation and analysis of a natural experiment. N Engl J Med 1972;287: 1013-7. 2. Nauts HC, Fowler GA, Bogatko FH. A review of the influence of bacterial infection and of bacterial products (Coley’s toxin) on malignant tumors in man. Acta Medica Scandinavica 1953;144: 1103. 3. Herter FP, Slanetz CA. Preoperative intestinal preparation in relation to subsequent development of cancer at the suture line. Surg Gynecol Obstet 1968;127:49-56. 4. Molin K, Rieger A. Effect of preoperative administration of oxytetracycline and neomycin on the development of local tumour recurrences in cases of cancer coli-recti. Acta Chir Scand 1979;145:327-30. 5. Cady G, Cliffton EE. Empyema and survival following surgery for bronchcgenic carcinoma. J Thorac Cardiovasc Surg 1967; 53: 102-8. 6. Papachristou DN, Fortner JG. Effect of postoperative wound infection on the course of stage I1 melanoma. Cancer 1979;43:110611. 7. Baker HW (Chairman of Task Force on Head and Neck Sites and Melanoma). Staging of cancer of head and neck sites and of melanoma. Chicago: American Joint Committee on Cancer, 1980636. 8. Sensenig DM, Rossi NP, Ehrenaft JL. Results of the surgical treatment of bronchogenic carcinoma. Surg Gynecol Obstet 1963;116:279-84. 9. Coley WB, Hoguet JP. Melanotic cancer. Ann Surg 1916;64:20641.
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Recent publications in the general surgery literature have reported improved survival in abdominal cancer surgery in those in whom a postoperative wound infection develops. We reviewed our experience with 100 consecutive patients operated on for head and neck cancer. All patients had 5-year followup. The complete report covers site and stage. In summary, for all cancers of the larynx (N = 60), the recurrence rate was 45% for those In whom a wound infection developed and 26% for those in whom no such infection developed. For cancers of the oral cavity and pharynx (N = 40), the recurrence rate was 80% for those in whom wound infections developed and 51% for those who had no infections. Because of the small number of patients in whom recurrence developed, with or without infection, the relationship does not reach statistical significance. For head and neck cancer, unlike abdominal cancer, the development of a postoperativewound infection may have an adverse effect on survival rather than a SalUtOry effect. [OTOLARYNGOL HEAD NECK SURG 1990;102:331.)
T h e effect of postoperative wound infection on tumor and recurrence has been debated for many years. Improved survival with postoperative infection has been reported with bronchogenic carcinoma, melanoma, and colon cancer. Others, however, have reported no difference in long-term survival in these same turn or^,^.^ although Papachristou and Fortnel-6 did find a decreased local recurrence rate. To our knowledge, there have been no reports devoted to the effect of postoperative wound infection on recurrence in head and neck squamous cell carcinoma. We reviewed our experience with 100 consecutive patients who received surgical treatment of their head and neck cancer. PATIENTS AND METHODS The patient records of 100 consecutive patients diagnosed as having head and neck squamous cell carcinoma were reviewed. Only patients treated with surgery for cure (all except stage I with postoperative radiation therapy) were included. Patients who did not have clear surgical margins (confirmed by the final his~~
From the Department of Otolaryngology-Head and Neck Surgery, University of Southern California School of Medicine, Los Angeles County-University of Southern California Medical Center. Submitted for publication Jan. 17, 1989; revision received Nov. 14, 1989; accepted Nov. 15, 1989. Reprint requests: Dale H. Rice, MD, Department of OtolaryngologyHead and Neck Surgery, University of Southern California School of Medicine, Los Angeles County-University of Southern California Medical Center, Box 795, 1200 North State St., Los Angeles, CA 90033. 23/1/ 18265
Table 1. Relation between stage and recurrence in patients with laryngeal cancer* Stage I
II
111
IV
Total
Developed postoperative - 213 011 215 419 infection (67%) (0%) (40%) (45%) No postoperative 013 2/19 6/20 519 13/51 infection (0%) (10%) (30%) (56%) (26%) *Figures indicate numbers of patients with cancerltotal number of patients (N = 60).
topathologic examination) were omitted from the study. Thus persistent tumor could presumably not account for the infection. Five-year follow-up data were available for all patients. Patients were clinically staged according to the standards set by the American Joint Committee on Cancer in 1980.’ The age range of patients was from 31 to 83 years of age. The average age was 59 years old. There were 75 men and 25 women. All patients had biopsy-proven squamous cell carcinoma before definitive treatment. The most common site of cancer was the larynx. Other sites included were the oral cavity, pharynx, nasal cavity, and maxillary sinus.
RESULTS The 100 patients were divided into two groups according to site. In group 1 were patients with laryngeal cancer; group 2 included patients with cancer of the oral cavity, pharynx, nose, or sinus. Sixty patients had 331
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
332
OtolaryngologyHead and Neck Surgery
JACKSON and RICE
Table 2. Relation between stage and recurrence in patients with cancer of the oral cavily, pharynx, nose, or maxillary sinus (N = 40) Stage
Developed postoperative infection No postoperative infection
I
II
111
IV
Total
-
112 (50%) 419 (44%)
1 /1 (100%) 6111 (56%)
212 (100%) 618 (75%)
415 (80%) 18/35 (51yo)
217 (29%)
Table 3. Relation between stage and recurrence in patients with cancer of all sites (N = 100) Stage
Developed postoperative infection No postoperative infection
I
II
111
IV
Total
-
315 (60%) 6/28 (21%)
1I 2 (50%) 12/31 (39%)
4/7 (57%) 11/17 (65%)
8/14 (57%) 31 186 (36%)
2/10 (20%)
Table 4. Relation between micoorganism cultured in postoperative wound infection and cancer recurrence Mlcroorganisrn
Present in patient cultures
Recurrence rate
P. aeruginosa Enterobacter sp. S. aureus Klebsiella sp. S. epidermidis S. viridans Veillonella sp.
5 4 3 3 1 1 1
80% 75% 33% 100% 100% 100% 100%
cancer of the larynx, whereas 40 patients were’ in the mixed site group (the majority of the latter had cancer of the oral cavity or pharynx). Each group was then divided into those in whom a postoperative wound infection developed and those in whom no such infection developed. Recurrence rates were calculated within both groups per individual stage, as well as total patients. All recurrences were at the primary site or in the treated neck. All infections involved the primary site and treated neck. In the first group of patients (laryngeal cancer), the overall recurrence rate of patients in whom a postoperative infection developed was 45%, as compared to 26% for those with no infection (Table 1). Because of the small number of infections, these values are not significant ( p = 0.2). In the second group of patients (Table 2-oral cavity, pharynx, and nose and sinus), the recurrence rates with
vs. without postoperative infection were: stage 11, 50% vs. 44%; stage 111, 100% vs. 56%; and stage IV, 100% vs. 75%. For all patients in this group, the recurrence rates were 80% vs. 5 1%, respectively. No stage I patient experienced a postoperative infection. Thus, both in terms of individual staging, as well as the total percentage of patients, recurrence rates were higher in patients in whom postoperative infection developed. Again, because of the small number of infections, the numbers do not reach significance (Fisher’s exact, p = 0.155). Lastly, for all 100 patients (Table 3), the recurrence rates with vs. without postoperative infection were: stage 11, 60% vs. 21%; stage 111, 50% vs. 39%; and stage IV, 57% vs. 65%. For all patients, the recurrence rates were 57% vs. 36% (Fisher’s exact, p = 0.20). Of the 14 patients in whom wound infection developed (either with or without fistula), culture results were available in 1 1 patients (Table 4). Pseudomonas aeruginosa was present in five, Enterobacter sp. in four, Staphylococcus aureus in three, Klebsiella sp. in three, Staphylococcus epidermidis in one, Streptococcus viridans in one, and Veillonella sp. in one. There was no relationship between a particular microorganism and cancer recurrence, other than a somewhat lower rate with Staphlococcus aureus (33%), as compared to the others (75% to 100%). DISCUSSION
Reports of improved survival of cancer patients in whom postoperative wound infection develops have been published in recent years. Ruckdeschel et al.’ and
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
Volume 102 Number 4 April 1990
Wound infections and recurrence in head and neck cancer 333
Sensenig et a1.8 have reported increased survival in patients who had pulmonary resections for bronchogenic carcinoma in whom empyema subsequently developed. However, Cady and Clifftod failed to find any difference in 5-year survival. Interestingly, their study did reveal a higher incidence of streptococcal and staphylococcal infection in the patients who did survive 5 years. Although, our numbers are too small to draw any definitive conclusions, it is notable that infections associated with Staphylococcus aureus did have a lower incidence of recurrence as compared with the other bacteria, which were mostly gram-negative bacilli, and was similar to the group without infection. There were no streptococcal (pyogenes) infections. Herter and Slanetz3 studied patients with colorectal carcinoma. Of 25 anastomotic recurrences, 22 occurred in patients who had been given antibiotic prophylaxis. It was concluded that suppression of colonic flora increased the risk of czncer recurrence. In other words, the normal bacteria acted to deter tumor implantation at the anastomotic site. However, Molin and Riegep found no difference in colorectal cancer recurrence rates between those who had and had not received antibiotic prophylaxis. Pathogenic bacteria were first popularized by Coley and Hoguet’ as anticancer agents more than 70 years ago. They noted that protection was afforded only to local lesions and not to distant metastases. Similarly, Papachristou and Fortner6 found that patients with stage I1 melanoma had lower incidence of local tumor recurrence than occurred in patients in whom postoperative infection developed; however, patient survival and the ultimate course of the disease were not affected. To our knowledge, there have been no previous reports on the effect of postoperative wound infection on head and neck squamous cell carcinoma recurrence rates. We found an overall higher incidence of tumor recurrence in those patients in whom postoperative infection developed, except in stage IV disease, in which the rates were similar. This is unlike most other studies (vide supra), which found no difference or a lesser incidence of recurrence with infection. Our results may reflect that patients with larger tumors-and thus with an inherently poorer prognoses-will need larger resections and thus infection will be more likely to develop. This is seen in our stage IV patients, in whom there is little difference between the infected and noninfected groups. However, in stage I1 lesions there is an appreciably increased recurrence rate in the presence of infection (60%vs. 21% for all sites). Thus, it may be that larger tumors would be less affected by variables such as local infection, but the number of patients with infection is too small to be certain. It is also possible
that streptococcal and staphylococcal infection have a different local tumoricidal effect than gram-negative bacilli, which were the predominant causative agents in the majority of wound infections we studied. CONCLUSION
One hundred patients with squamous cell carcinoma of the head and neck treated for cure with either surgery or combined therapy (surgery and radiation) were reviewed. Recurrence rates were higher for patients with oral cavity, pharynx, nose, or sinus cancer in whom a postoperative infection developed. In patients with laryngeal cancer-although stage I1 patients with postoperative infection had higher recurrence rates-stage 111 and IV patients had lower rates, but the number of patients with infections was small. However, overall the laryngeal cancer patients had higher recurrence rates if postoperative wound infection developed. In all cases, however, the numbers were too small to reach statistical significance. Whether or not this association is causative is unknown, but it does imply that postoperative wound infection may adversely affect the patient with squamous cell carcinoma of the head and neck. Much larger numbers of patients would need to be studied to definitely answer this question.
REFERENCES
1. Ruckdeschel JC, Codish SD, Strauhan A, McKneally MF. Postoperative empyema improves survival in lung cancer: documentation and analysis of a natural experiment. N Engl J Med 1972;287: 1013-7. 2. Nauts HC, Fowler GA, Bogatko FH. A review of the influence of bacterial infection and of bacterial products (Coley’s toxin) on malignant tumors in man. Acta Medica Scandinavica 1953;144: 1103. 3. Herter FP, Slanetz CA. Preoperative intestinal preparation in relation to subsequent development of cancer at the suture line. Surg Gynecol Obstet 1968;127:49-56. 4. Molin K, Rieger A. Effect of preoperative administration of oxytetracycline and neomycin on the development of local tumour recurrences in cases of cancer coli-recti. Acta Chir Scand 1979;145:327-30. 5. Cady G, Cliffton EE. Empyema and survival following surgery for bronchcgenic carcinoma. J Thorac Cardiovasc Surg 1967; 53: 102-8. 6. Papachristou DN, Fortner JG. Effect of postoperative wound infection on the course of stage I1 melanoma. Cancer 1979;43:110611. 7. Baker HW (Chairman of Task Force on Head and Neck Sites and Melanoma). Staging of cancer of head and neck sites and of melanoma. Chicago: American Joint Committee on Cancer, 1980636. 8. Sensenig DM, Rossi NP, Ehrenaft JL. Results of the surgical treatment of bronchogenic carcinoma. Surg Gynecol Obstet 1963;116:279-84. 9. Coley WB, Hoguet JP. Melanotic cancer. Ann Surg 1916;64:20641.
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