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December 1973, Vol 108, No. 6 >
Article | December 1973

Hypertrophic Scar After Cryotherapy and Topical Tretinoin

Gary L. Peck, MD
[+] Author Affiliations

Accepted for publication July 31, 1973.

Reprint requests to Dermatology Branch, National Cancer Institute, Bldg 10, Room 12N238, National Institutes of Health, Bethesda, MD 20014 (Dr. Peck).


Bethesda, Md

From the Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md.


Arch Dermatol. 1973;108(6):819-822. doi:10.1001/archderm.1973.01620270041010
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A large recurrent basal cell epithelioma resolved following treatment with topically applied 1% tretinoin (vitamin A acid) ointment. The lesion had been pretreated with superficial liquid nitrogen cryotherapy eight weeks previously. Coincident with the resolution of the tretinoin-induced inflammatory reaction, a hypertrophic scar developed that involuted after nine months. A hypertrophic scar was experimentally produced on normal appearing skin by the sequential administration of cryotherapy and the topical application of tretinoin, but by neither mode of therapy alone. These findings support recent studies that show a stimulatory effect of vitamin A on fibroblastic function, as well as those that demonstrate a beneficial effect of vitamin A in the treatment of malignant tumors.

REFERENCES

1 +
Logan WS:  Vitamin A and keratinization . Arch Dermatol 105:748-753, 1972;.
2 +
Jarrett A, Spearman RIC:  Vitamin A and the skin . Br JDermatol 82:197-199, 1970;.
3 +
Zil JS:  Vitamin A acid effects on epidermal mitotic activity, thickness, and cellularity in the hairless mouse . J Invest Dermatol 59:228-232, 1972;.
4 +
Daniel MR, et al:  The action of excess of Vitamin A alcohol on the fine structure of rat dermal fibroblasts . J Cell Biol 30:465-475, 1966;.
5 +
Ehrlich HP, Tarver H:  Effects of βcarotene, vitamin A, and glucocorticoids on collagen synthesis in wounds . Proc. Soc. Exp Biol Med 137: 936-938, 1971;.
6 +
Firschein HE:  Collagen and mineral accretion rates in bone during vitamin A deficiency . Am J Physiol 219:1183-1187, 1970;.
7 +
DeLuca L, Barber AJ, Jamieson GA:  Possible role of vitamin A in platelet-collagen adhesion . Fed Proc 31:177, 1972;.
8 +
Stein HD, Keiser HR:  Collagen metabolism in granulating wounds . J Surg Res 11:277-283, 1971;.
9 +
Hunt TK, et al:  Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man . Ann Surg 170:633-641, 1969;.
10 +
Stephens FO, et al:  Effect of cortisone and vitamin A on wound infection . Am J Surg 121: 569-571, 1971;.
11 +
Lee KH, Tong TG:  Studies on the mechanism of action of salicylates: VI: Effect of topical application of retinoic acid on wound healing retardation action of salicylic acid . J Pharm Sci 58:773-774, 1969;.
12 +
Prutkin L:  Wound healing and vitamin A acid . Acta Derm Venereol 52:489-492, 1972;.
13 +
Cohen IK, Keiser HR, Sjoerdsma A:  Collagen synthesis in human keloid and hypertrophic scar . Surg Forum 22:488-489, 1971;.
14 +
Garcia-Velasco J:  Keloids and hypertrophic scars , in Maibach HI, Rovee DT (eds): Epidermal Wound Healing . Chicago, Year Book Medical Publishers Inc, 1972;, pp 281-289.
15 +
Baer RL, Kopf AW:  Complications of therapy of basal cell epitheliomas , in Baer RL, Kopf AW (eds): Year Book of Dermatology . Chicago, Year Book Medical Publishers 1965;, pp 7-26.
16 +
Hunt TK:  Current challenges for wound healing research . J Trauma 10:1001-1009, 1970;.
17 +
Blackburn WR, Cosman B:  Histologic basis of keloid and hypertrophic scar differentiation . Arch Pathol 82:65-71, 1966;.
18 +
Ehrlich HP, Tarver H, Hunt TK:  Inhibitory effects of vitamin E on collagen synthesis and wound repair . Ann Surg 175:235-240, 1972;.
19 +
Lee KH:  Studies on the mechanism of action of salicylates: III. Effect of vitamin A on the wound healing retardation aspect of aspirin . J Pharm Sci 57:1238-1240, 1968;.
20 +
Lee KH, Tong TG:  Mechanism of action of retinyl compounds on wound healing: I. Structural relationship of retinyl compounds and wound healing . J Pharm Sci 59:851-854, 1970;.
21 +
Herrmann JB, Woodward SC:  An experimental study of wound healing accelerators . Am Surg 38:26-34, 1972;.
22 +
Hoopes JE, Im MJC:  β-Glycosidases in keloid and hypertrophic scars . Plast Reconstr Surg , to be published.
23 +
Persidsky MD:  Lysosomes as a target of cryoinjury . Cryobiology 6:582, 1969;.
24 +
Persidsky MD, Ellett MH:  Lysosomal involvement in cryoinjury . Cryobiology 6:280, 1969;.
25 +
Friedman NB:  The pathology of trench foot . Am J Pathol 21:387-433, 1945;.
26 +
Blair JR, Schatzki R, Orr KD:  Sequelae to cold injury in one hundred patients . JAMA 163: 1203-1208, 1957;.
27 +
Carpenter HM, et al:  Vascular injury due to cold . Arch Pathol 92:153-161, 1971;.
28 +
Zacarian SA:  Cryosurgery for cutaneous carcinoma . Dermatol Dig 9:49-56, 1970;.
29 +
Zacarian SA: Cryosurgery of Skin Cancer and Cryogenic Techniques in Dermatology . Springfield, Ill, Charles C Thomas, Publisher, 1969;, p 80.
30 +
Fitzpatrick TB, et al (eds): Dermatology in General Medicine . New York, McGraw-Hill Book Co Inc, 1971;, p 522.
31 +
Bollag W:  Therapy of chemically induced skin tumors of mice with vitamin A palmitate and vitamin A acid . Experientia 27:90-92, 1971;.
32 +
Prutkin L:  The effect of vitamin A acid on hyperkeratinization and the keratocanthoma . J Invest Dermatol 49:165-172, 1967;.
33 +
Bollag W, Ott F:  Retinoic acid: Topical treatment of senile or actinic keratoses and basal cell carcinomas . Agents Actions 1:172-175, 1970;.
34 +
Saffiotti U, et al:  Experimental cancer of the lung: Inhibition of vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors . Cancer 20:856-864, 1967;.
35 +
Chu E, Malmgren RA:  An inhibitory effect of vitamin A on the induction of tumors of the forestomach and cervix in syrian hamster by carcinogenic polycyclic hydrocarbons . Cancer Res 25:884-895, 1965;.
36 +
Cone MV, Nettesheim P:  Effects of vitamin A on 3-methylcholanthrene-induced squamous metaplasias and early tumors in the respiratory tract of rats . J Natl Cancer Inst 50: 1599-1606, 1973;.
37 +
Cohen MH, Carbone PP:  Enhancement of antitumor effects of 1,3-bis (2-chloroethyl)-nitrosourea and cyclophosphamide by vitamin A . J Natl Cancer Inst 48:921-926, 1972;.
38 +
Prutkin L:  Antitumor activity of vitamin A acid and fluorouracil used in combination on the skin tumor, keratoacanthoma . Cancer Res 33:128-133, 1973;.
39 +
Brandes D, et al:  Role of lysosomal labilizers in treatment of mammary gland carcinomas with cyclophosphamide: Preliminary report . Cancer ChemotherRep 50:47-53, 1966;.

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1 +
Logan WS:  Vitamin A and keratinization . Arch Dermatol 105:748-753, 1972;.
2 +
Jarrett A, Spearman RIC:  Vitamin A and the skin . Br JDermatol 82:197-199, 1970;.
3 +
Zil JS:  Vitamin A acid effects on epidermal mitotic activity, thickness, and cellularity in the hairless mouse . J Invest Dermatol 59:228-232, 1972;.
4 +
Daniel MR, et al:  The action of excess of Vitamin A alcohol on the fine structure of rat dermal fibroblasts . J Cell Biol 30:465-475, 1966;.
5 +
Ehrlich HP, Tarver H:  Effects of βcarotene, vitamin A, and glucocorticoids on collagen synthesis in wounds . Proc. Soc. Exp Biol Med 137: 936-938, 1971;.
6 +
Firschein HE:  Collagen and mineral accretion rates in bone during vitamin A deficiency . Am J Physiol 219:1183-1187, 1970;.
7 +
DeLuca L, Barber AJ, Jamieson GA:  Possible role of vitamin A in platelet-collagen adhesion . Fed Proc 31:177, 1972;.
8 +
Stein HD, Keiser HR:  Collagen metabolism in granulating wounds . J Surg Res 11:277-283, 1971;.
9 +
Hunt TK, et al:  Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man . Ann Surg 170:633-641, 1969;.
10 +
Stephens FO, et al:  Effect of cortisone and vitamin A on wound infection . Am J Surg 121: 569-571, 1971;.
11 +
Lee KH, Tong TG:  Studies on the mechanism of action of salicylates: VI: Effect of topical application of retinoic acid on wound healing retardation action of salicylic acid . J Pharm Sci 58:773-774, 1969;.
12 +
Prutkin L:  Wound healing and vitamin A acid . Acta Derm Venereol 52:489-492, 1972;.
13 +
Cohen IK, Keiser HR, Sjoerdsma A:  Collagen synthesis in human keloid and hypertrophic scar . Surg Forum 22:488-489, 1971;.
14 +
Garcia-Velasco J:  Keloids and hypertrophic scars , in Maibach HI, Rovee DT (eds): Epidermal Wound Healing . Chicago, Year Book Medical Publishers Inc, 1972;, pp 281-289.
15 +
Baer RL, Kopf AW:  Complications of therapy of basal cell epitheliomas , in Baer RL, Kopf AW (eds): Year Book of Dermatology . Chicago, Year Book Medical Publishers 1965;, pp 7-26.
16 +
Hunt TK:  Current challenges for wound healing research . J Trauma 10:1001-1009, 1970;.
17 +
Blackburn WR, Cosman B:  Histologic basis of keloid and hypertrophic scar differentiation . Arch Pathol 82:65-71, 1966;.
18 +
Ehrlich HP, Tarver H, Hunt TK:  Inhibitory effects of vitamin E on collagen synthesis and wound repair . Ann Surg 175:235-240, 1972;.
19 +
Lee KH:  Studies on the mechanism of action of salicylates: III. Effect of vitamin A on the wound healing retardation aspect of aspirin . J Pharm Sci 57:1238-1240, 1968;.
20 +
Lee KH, Tong TG:  Mechanism of action of retinyl compounds on wound healing: I. Structural relationship of retinyl compounds and wound healing . J Pharm Sci 59:851-854, 1970;.
21 +
Herrmann JB, Woodward SC:  An experimental study of wound healing accelerators . Am Surg 38:26-34, 1972;.
22 +
Hoopes JE, Im MJC:  β-Glycosidases in keloid and hypertrophic scars . Plast Reconstr Surg , to be published.
23 +
Persidsky MD:  Lysosomes as a target of cryoinjury . Cryobiology 6:582, 1969;.
24 +
Persidsky MD, Ellett MH:  Lysosomal involvement in cryoinjury . Cryobiology 6:280, 1969;.
25 +
Friedman NB:  The pathology of trench foot . Am J Pathol 21:387-433, 1945;.
26 +
Blair JR, Schatzki R, Orr KD:  Sequelae to cold injury in one hundred patients . JAMA 163: 1203-1208, 1957;.
27 +
Carpenter HM, et al:  Vascular injury due to cold . Arch Pathol 92:153-161, 1971;.
28 +
Zacarian SA:  Cryosurgery for cutaneous carcinoma . Dermatol Dig 9:49-56, 1970;.
29 +
Zacarian SA: Cryosurgery of Skin Cancer and Cryogenic Techniques in Dermatology . Springfield, Ill, Charles C Thomas, Publisher, 1969;, p 80.
30 +
Fitzpatrick TB, et al (eds): Dermatology in General Medicine . New York, McGraw-Hill Book Co Inc, 1971;, p 522.
31 +
Bollag W:  Therapy of chemically induced skin tumors of mice with vitamin A palmitate and vitamin A acid . Experientia 27:90-92, 1971;.
32 +
Prutkin L:  The effect of vitamin A acid on hyperkeratinization and the keratocanthoma . J Invest Dermatol 49:165-172, 1967;.
33 +
Bollag W, Ott F:  Retinoic acid: Topical treatment of senile or actinic keratoses and basal cell carcinomas . Agents Actions 1:172-175, 1970;.
34 +
Saffiotti U, et al:  Experimental cancer of the lung: Inhibition of vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors . Cancer 20:856-864, 1967;.
35 +
Chu E, Malmgren RA:  An inhibitory effect of vitamin A on the induction of tumors of the forestomach and cervix in syrian hamster by carcinogenic polycyclic hydrocarbons . Cancer Res 25:884-895, 1965;.
36 +
Cone MV, Nettesheim P:  Effects of vitamin A on 3-methylcholanthrene-induced squamous metaplasias and early tumors in the respiratory tract of rats . J Natl Cancer Inst 50: 1599-1606, 1973;.
37 +
Cohen MH, Carbone PP:  Enhancement of antitumor effects of 1,3-bis (2-chloroethyl)-nitrosourea and cyclophosphamide by vitamin A . J Natl Cancer Inst 48:921-926, 1972;.
38 +
Prutkin L:  Antitumor activity of vitamin A acid and fluorouracil used in combination on the skin tumor, keratoacanthoma . Cancer Res 33:128-133, 1973;.
39 +
Brandes D, et al:  Role of lysosomal labilizers in treatment of mammary gland carcinomas with cyclophosphamide: Preliminary report . Cancer ChemotherRep 50:47-53, 1966;.

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