/ 4b O SUCROSE O SACCHARIN V SHAM INJ. DAYS POST INJECTION parent changes in taste perception may result from the cancer itself or from the associated therapy. If the cancer is localized in the oral cavity, many of the problems regarding taste are evident. Cancers located elsewhere have been reported to cause taste changes. but the evidence is strong that these changes are hedonic and not the result of taste receptor problems (27, 30—32). Many of the reports of taste changes in cancer patients have focused on changes in taste detection thresholds. i.e. , what is the minimum concentration of a taste compound that is perceived by the patient. Bartoshuk (27) said that these threshold changes "have limited relevance for real-world taste." She measured both detection threshold and suprathreshold taste function in a patient with neck cancer. The detection threshold returned to normal in 2 months following treatment. but the suprathreshold functions did not return to normal. Salivary Glands Since the turnover rate of salivary gland cells is qu;te low, one would not expect much damage by Xray' irradiation. However, loss of salivary flow is a common problem experienced by patients undergoing cither irradiation or chemotherapy treatment. Experimental studies with rats show loss of gland weight, changes in salivary protein composition, decrease in flow rate, and cellular degeneration. The acinar cells are the most sensitive cells of the salivary gland. The parotid gland is more radiosensitive than the submandibular or sublingual gland. The salivary glands are susceptible to damage by head and neck irradiation. If severe. this may lead to complete lack of salivary flow. Saliva is a complex FIG. 6. Daily rat preference for saccharin in the days following a saline injection (open triangles) is compared with preference for saccharin following a vinblastine injection (closed
very time the salivary gland is in most need of nourishment during irradiation or chemotherapy. Although the common complaint is that food does not taste good. many of the preceding additional factors are also important and the sensory involvement is not limited to taste alone. Many, but not all. of these patients may recover their taste and joy of food several months after irradiation is terminated. Changes in Blood Chemistry Changes in perceived taste by cancer patients could also be due to changes in blood chemistry. Bradley (44) has shown experimentally that some chemicals injected intravascularly stimulate the taste cells. [n clinical tests. chemicals injected into the blood were often used to measure arm-to-tongue circulation time. It is not surprising that some patients complain about bitter tastes during a chemotherapy treatment and many patients report both bitter and metallic tastes long after the treatment is completed. Conditioned Ayersions When studying decrements in sensation associated with radiotherapy and chemotherapy drugs, it is important to be aware of the fact that these decrements are quite possibly the result of a learning process. Learned taste (or food) aversions can occur as a result of ionizing radiation exposure (45). Saccharinflavored water, a normally preferred taste solution by rats. was presented simultaneously with a sublethal exposure to gamma rays. Several days after this pairing of the taste of saccharin with the irradiation. the rats avoided the normally preferred solution in subsequent preference tests. Animals that received only gamma e.xposure, i.e. . no saccharin was paired with the irradiation. showed a strong preference for the sweetened solution in subsequent tests. One could in- 700 / 48 fer that an animal experiencing nausea or another repugnant sensation due to irradiation exposure associates it with the ingestion of a food or liquid and therefore avoids its further ingestion. Smith and Morrig (46) reported that a taste aversion could be conditioned by pairing
investigations have also shown that taste aversions are readily learned in chemotherapy patients (55—58). As in the previous studies with rats, it was found that novel tastants paired with chemotherapy resulted in stronger taste aversions than the aversions to familiar foods (58). Learned taste aversions to fruit juices have also been conditioned in radiotherapy patients (59—61). A way to avoid the formation of taste aver.sions in cancer patients would be to intentionally pair a " scapegoat" food with the therapy, conditioning an aversion to this unimportant food source (62). It was successfully demonstrated with children patients. It should be noted that learned taste aversions are probably the rule, rather than the exception, in cancer patients. The fact that intravascular 'tastes" have been conditioned in rats has strong implications for learned aversions in chemotherapy patients. The intensity and longevity of these learned aversions as related to the appetite problems in cancer patients needs to be more fully explored. Oral Epithelium The oral epithelium is well designed to absorb the insults that accompany the intake of hot coffee, cold ice cream, tough and hard food. etc. Yet the sensitivities of thermal and tactile receptors of the tongue remain high. This beautiful balance is disrupted if the epithelium is defaced and substances taken into the mouth can easily penetrate toward the base of the epithelium. Stomatitis, the inflammation of the mucous membrane of the mouth. presents an excellent mode of entrance for foreign chemicals. bacteria, viruses, etc., into the basc of the epithelium and eventually into the vascular system (62). The associated pain disrupts the normal appreciation of food taken into the mouth. and both the pattern and amount of consumption can change. If severe. inadequate nutrition results. In addition, many of the habits associated with normal dental and oral hygiene will be disrupted, which leads to further deterioration of both teeth and the mucous membranes. Conclusions It can be seen from the preceding discussion that the alterations in taste sensitivity reported by cancer patients are likely due to multiple causes. These could differ markedly depending upon the location and type of malignancy. the course of radiation or chemotherapy, and the psychologic state
of the patient. The following suggestions could help to reduce taste changes and losses and possible subsequent diminishing of appetite. Food Intake, and Nutrition: Suggestions for Their Improvement l . Psychologic trauma occurs even before treatment begins and thus interest in eating declines. Patient should be told what to expect during treatment. It is important that the patient understands when to expect improvement in his or her conditions as a function of time. Acute and chronic effects are listed in Table l . A state of hope is very important. Tolerance dose, fractionation pattern, and target volume must be selected with attention to minimum damage to salivary and taste organs when using radiation. Selective shieldings of parotid glands as well as some of the taste buds are most important. Mucositis appears during irradiation treatment but also declines sooner than taste dysfunction. Bland foods with neutral pH are best tolerated. Milk is a good food source under these conditions. Alcohol should be forbidden. Severe xerostomia can be of long duration and should be avoided if possible. The parotid glands are the major source of salivary production during periods TABLE 1. Summary of effects of radiation therapy Region Acute effects Chronic effects Central nervous system Nausea, vomiting Head and neck Mucositis, sore Xerostomia, loss of mouth and taste, dental throat, caries, ulcer, dysphagia, osteoradionecrosis, odynophagia, dry (xerostomia), loss of taste (hypo-I ageusia), dysgeusia, dysosmia, anorexia trismus Thorax Dysphagia Fibrosis, stenosis, perforation, fistula Abdomen and Anorexia, Diarrhea, nausea. maldigestion, vomiting, maiabsorption, diarrhea, acute chronic enteritis, enteritis, acute chronic colitis: colitis, ulcer, stricutret choleretic obstruction, enteropathy diarrhea, perforation, fistula of sensory stimulation. Artificial saliva should be suggested to patients, but it is of limited use. Since severity of xerostomia is directly related to total radiation dose and to volume of salivary gland irradiated, adequate