Pleasure and alcohol: manipulating pleasantness and the acute effects of alcohol on food intake.

To examine the effects of manipulating pleasantness on subsequent energy intake following a moderate dose of alcohol, 12 males attended the laboratory on four occasions. On each occasion participants consumed breakfast then 4 h later were offered lunch. Twenty minutes before lunch participants received an alcohol (24 g ethyl alcohol, 1508 kJ, 405 ml) or a no-alcohol (867 kJ, 405 ml) containing beverage followed by a lunch of either "bland" (rated pleasantness=66+/-13 mm) or "flavoured" (73+/-10 mm) foods. Subjective ratings of appetite, mood and pleasantness of several bland and tasty foods were taken before and after preloads and lunch. Ad libitum energy intake at lunch was greater following alcohol in both taste conditions (p<0.01) (Alcohol/Bland, 2053+/-663 kJ; Alcohol/Flavoured, 1989+/-580 kJ) in comparison to the no-alcohol conditions (No-alcohol/Bland, 1548+/-357 kJ; No-alcohol/Flavoured 1670+/-401 kJ). No additive effect of palatability and alcohol was found; alcohol did not differentially affect intake of lunch items. Nor did alcohol increase the pleasantness of foods. Sensory specific satiety (SSS) was observed both following the preload and following lunch, with no discernible effects of alcohol on SSS. In conclusion, alcohol promoted food intake but this did not occur via the additive effects of alcohol and palatability nor through increasing the pleasantness of the taste of foods. Further research on the mechanism underlying the stimulating effects of alcohol on appetite is warranted.

Parotid-sparing irradiation for cancer of the oral cavity: maintenance of oral nutrition and body weight by preserving parotid function.

The purpose of this study was to assess the nutritional benefit of parotid-sparing irradiation, comparing the body weights of patients irradiated with parotid-sparing technique versus those irradiated with bilateral opposed photon beams, including both parotid glands in the radiation fields. One hundred fourteen patients with cancer of the oral cavity were irradiated with curative intent. Two-dimensional radiotherapy techniques sparing at least one parotid gland from the radiation beams were used to treat 31 patients (parotid-sparing techniques). Eighty-three patients were irradiated using bilateral opposed photon beams, which included both parotid glands (bilateral technique). Body weight during and after irradiation, treatment outcome, and survival were compared. Patients treated with parotid-sparing techniques maintained their nutritional intake and baseline body weight during and after irradiation. Patients treated with the bilateral technique that included both parotid glands had poor nutritional intake, leading to a more than 10% decline in their initial body weight; these patients did not regain their body weight during the 2-year follow-up period. Primary tumor control rate was higher for patients treated with parotid-sparing techniques than for patients who had both parotid glands irradiated (70% versus 48%; p = 0.05). This difference is because a higher percentage of patients treated with parotid-sparing techniques had early-stage tumors (54%) compared with patients treated with the bilateral technique (24%). When analyzed according to the tumor stage, the primary tumor control rates for patients treated with parotid-sparing techniques and for patients treated with the bilateral technique showed no difference; control rates were 93% and 87% (p = 1.00) for early-stage tumors and 42% and 36% (p = 0.75) for advanced-stage tumors, respectively. Nodal control rates in the ipsilateral side of the neck and in the contralateral side of the neck for patients treated with parotid-sparing techniques and with the bilateral technique were not significantly different-74% versus 76% (p = 0.86) and 70% versus 82% (p = 0.21), respectively. Sparing at least one parotid gland during irradiation of patients with head and neck cancer will preserve parotid function and prevent xerostomia. Patients treated with parotid-sparing techniques were able to maintain their oral nutrition and body weight, compared with patients who had both parotid glands irradiated. A higher percentage of patients treated with parotid-sparing techniques had early-stage tumors, resulting in higher rates of primary tumor control and survival in this group of patients.

Results of treatment of patients with maxillary sinus carcinoma.

BACKGROUND: Information regarding results of treatment and possible prognostic factors in patients with maxillary sinus carcinoma is limited. METHODS: Between 1969-1995, 48 consecutive patients presented to the study department for curative treatment of maxillary sinus carcinoma. Tumor classification according to the American Joint Committee on Cancer staging system was T1 in 1 patient, T2 in 6 patients, T3 in 17 patients, and T4 in 24 patients. The N classification was NO in 43 patients, N2a in 1 patient, N2b in 3 patients, and N2c in 1 patient. Treatment to the primary site was comprised of surgery (Sx) and radiation therapy (RT) in 37 patients and RT alone in 11 patients. RESULTS: There was a difference in disease free survival between patients who underwent Sx + RT compared with patients who received RT alone; combined therapy results were more favorable. The most common pattern of recurrence was in the primary site, which was found in 22 of 48 patients (45.8%). For patients who underwent Sx + RT, local control at 3 and 5 years was 65.2% and 59.2%, respectively; for patients who received RT alone, local control at both 3 and 5 years was 22.7%. There were 12 late complications found in 8 patients: fistula formation (5 patients), trismus (3 patients), osteonecrosis (1 patient), retinopathy (1 patient), cellulitis (1 patient), and nasal stenosis (1 patient). CONCLUSIONS: The type of treatment to the primary site is an important determinant of disease free survival and local control. Failure at the primary site is the main problem in the curative treatment of patients with maxillary sinus carcinoma; efforts to improve survival in these patients should be directed toward improvement of local control.

The National Cancer Data Base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma.

BACKGROUND: The development of nasopharyngeal carcinoma reflects interactions of genetics, diet, and viral agents. It is more common in Asians than non-Asians, with different characteristic histologic types. This study examined nasopharyngeal carcinoma in the U.S. as a function of patient origin and histology. METHODS: The data were from the National Cancer Data Base (NCDB). The 5069 nasopharyngeal carcinoma cases were grouped by histologic type: keratinizing squamous cell, nonkeratinizing, and undifferentiated carcinoma. Patient origin was derived from race, Hispanic ethnicity, and place of birth. RESULTS: World Health Organization (WHO) type 1 keratinizing squamous cell carcinomas comprised 75% of the U.S. nasopharyngeal carcinoma cases and were found most often in U.S.-born, non-Hispanic whites. WHO-2 nonkeratinizing and WHO-3 undifferentiated carcinomas of the nasopharnyx comprised the remaining 25% of nasopharyngeal carcinomas and were more common in Asians. Histologic composition varied for each of the 12 patient origin groups in the study and correlated with survival after treatment with ionizing radiation. Asians had the highest proportion of radioresponsive WHO-2 nonkeratinizing and WHO-3 undifferentiated carcinomas of the nasopharynx and better survival than African-Americans and Hispanic and non-Hispanic whites, who had the greatest number of the less radioresponsive keratinizing squamous cell carcinomas of the nasopharynx. The 5-year relative survival was 65% for the nonkeratinizing and undifferentiated carcinomas of the nasopharynx and 37% for the keratinizing variety. CONCLUSIONS: The survival rate of the patient origin groups correlated with the histologic composition of their nasopharyngeal carcinomas. Those with the highest proportion of radioresponsive nonkeratinizing and undifferentiated carcinomas had the best survival.

Effect of tumor bulk on local control and survival of patients with T1 glottic cancer.

PURPOSE: To evaluate the effect of tumor bulk in relation to various tumor-related prognostic factors and treatment-related variables on local control and survival of patients with T1 N0 M0 squamous cell carcinoma of the glottis. MATERIALS AND METHODS: In 114 patients with T1 squamous cell carcinoma of the glottic larynx who were irradiated with curative intent, we determined the effect of tumor bulk in relation to mucosal extent (stage and anterior commissure involvement), histologic differentiation and various radiation factors, especially overall treatment time on local control and survival. Tumors were classified retrospectively as small surface lesions or bulky tumors. Seventy-seven patients had small lesions and 37 had bulky tumors. The anterior commissure was involved with cancer in 43 patients. The overall duration of irradiation ranged from 39 to 64 days. The median follow-up time was 6 years (range 5-24 years). RESULTS: The 5-year actuarial local control rate for all patients was 82% after radiotherapy and 92% after salvage laryngectomy. On univariate analysis, bulky tumors and tumors involving the anterior commissure showed an adverse effect on local control, whereas the overall duration of irradiation had a borderline significance. The actuarial local control rate was 91% for small tumors and 58% for bulky tumors (P = 0.0002), 88% when the anterior commissure was not involved and 67% when the anterior commissure was involved (P = 0.01) and 89% when radiation was given in less than 50 days and 73% when irradiation exceeded 50 days (P = 0.06). On multivariate analysis. tumor bulk was the only significant factor that affected local control (P = 0.02). The 5-year actuarial survival for all patients was 73% and the disease-free survival was 92%. CONCLUSION: This study shows that tumor bulk has a highly significant effect on the radiation control of T1 glottic cancer. Patients who had bulky tumors had lower local control and disease-free survival rates than those patients who had small tumors.

Is prophylactic neck irradiation indicated in patients with squamous cell carcinoma of the maxillary sinus?

PURPOSE: To determine the proportion of patients with squamous cell carcinoma of the maxillary sinus who will fail in regional nodes without elective neck treatment and to identify any prognostic factors that may influence neck control. METHODS AND MATERIALS: From 1971-1995, 42 consecutive patients with squamous cell carcinoma of the maxillary sinus were seen at our department for curative treatment. There were 35 males and 7 females, with a median age at diagnosis of 63.5 years (range, 42-77 years). One tumor was classified as T1, 5 had T2, 15 had T3, and 21 had T4 disease. Four of 42 patients (9.5%) had cervical lymphadenopathy at initial presentation. Thirty-three patients had surgical resection and radiotherapy and nine had radiotherapy alone. None of the 38 patients with clinical N0 necks received elective treatment to the cervical nodes. RESULTS: Median overall survival was 30 months for all patients. Of the 38 patients with N0 disease, 11 (28.9%) had neck recurrence. Of the 11 neck failures, 9 were ipsilateral only, 1 was contralateral, and 1 had bilateral neck recurrence. The most common site of neck failure was in the upper neck (submandibular and jugulodigastric lymph nodes). Four of the 38 patients (10.5%) had isolated neck failure. Only tumor stage was found to be significant for neck relapse, with T1 and T2 doing worse compared to T3 and T4 tumors. Location of tumor (infrastructure vs. suprastructure), involvement of the oral cavity/oropharynx, nasal cavity, nasopharynx or orbit did not predict for cervical node relapse. Local control at the primary site was likewise not prognostic. The median overall survival for patients who remained N0 was 80 months and for those with initial cervical involvement or recurred in the neck without elective neck irradiation was 25 months (p = 0.05). CONCLUSION: Based on the 28.9% rate of neck recurrence and the poor median survival of patients who recur in the neck, we recommend prophylactic ipsilateral neck irradiation in patients with T1-T4 squamous cell carcinoma of the maxillary sinus.

Mucosal protectants and their application for head and neck chemoirradiation.

Mucosal injury due to ionizing radiation or cytotoxic agents begins with damage to stem cells in the basal epithelium, progresses as these cells are depleted, and is complicated by inflammation and superimposed infection. Suppression of oral and pharyngeal infection, cytokine stimulation of neutrophils, and protection of basal epithelium by chemical or physical means have been developed to protect mucosa from the acute effects of chemoirradiation. Although no method has been capable of preventing mucosal injury or its inflammatory consequences, many have proven partially effective and are reviewed in this article. Introduction of mucosal protectants into clinical use is needed to reduce the morbidity of chemoirradiation and to enhance its effectiveness by dose intensification, accelerated delivery, and simultaneous use.

Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation.

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.

Postoperative irradiation of patients with malignant tumors of skull base.

To better understand how to irradiate patients after skull-base surgery, the authors of this study analyzed the tumor recurrence patterns in 22 patients with various malignancies. Of these patients, 13 underwent craniofacial resection, 6 had infratemporal fossa resection, and 3 had temporal bone resection. The entire operative field was irradiated in 8 patients (total-field group), and part of the operative field was irradiated in 14 patients (partial-field group). Tumor regrew within the irradiated area in 25% of the total-field group and 14% of the partial-field group. Tumor appeared outside the operative field in 13% of the total-field group and 57% of the partial-field group. Recurrences appeared in contiguous sites in 5 patients, in the unirradiated scar in 5 patients, and in the lymph nodes in 4 patients. Based on the study findings, the authors state that irradiation of the entire operative field, including scars and potential areas of contiguous spread, may be necessary to maximize local control after skull-base surgery.

Protection from Radiation-Induced Oral Mucositis by Misoprostol, a Prostaglandin E(1) Analog: A Placebo-Controlled, Double-Blind Clinical Trial.

Misoprostol, a prostaglandin E(1) analog, is an effective radioprotector in animal studies. Based on this evidence, a prospective, randomized, placebo-controlled, double-blind study was conducted to determine if misoprostol protected the oral and pharyngeal mucosa of irradiated head and neck cancer patients from radiation mucositis. Postsurgical patients who had no detectable cancer and who were referred for postoperative irradiation were candidates for this study. Thirty-four Hines VA and 35 Loyola University patients were accrued (69 total) over a 2-year period. A misoprostol tablet (200 &mgr;g) or an identical placebo tablet was dissolved in water and administered as an oral rinse daily about 20 min before irradiation. Conventional fractionated radiotherapy, consisting of five weekly doses of 2 Gy day(minus sign1), was delivered. The degree of mucositis was scored on a scale from 0 (no mucositis) to 4. In the 17 patients randomly assigned to the misoprostol arm at the Hines VA, no advantage was seen compared to the 17 placebo-treated patients. However, there was significantly less mucositis (p < 0.01, analysis of variance) from weeks 3--6 in the 17 patients treated with misoprostol at Loyola compared to the 18 placebo-treated patients. Several problems in the study were identified at the VA, including adherence to the protocol design. Other problems such as adequate mucositis scoring, radiation scatter from fillings, and, in particular, adequate timing between misoprostol and irradiation were identified at both locations. Absorption studies in healthy volunteers showed significant plasma levels at 10 min after an oral rinse, suggesting that initial clinical trials should be confined to topical misoprostol until more is known regarding the effect of misoprostol on tumors. The results of this pilot study suggest that misoprotol may protect the oral and pharyngeal mucosa from radiation-induced mocositis if adequate time between topical administration and radiation is allowed.

Radiotherapy alone compared with radiotherapy and chemotherapy in patients with squamous cell carcinoma of the esophagus.

PURPOSE: The purpose of this study is to determine whether primary treatment with both radiotherapy and chemotherapy is superior to radiotherapy alone in patients with squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: From January 1980 to December 1988, 77 patients from two Veterans Affairs hospitals with clinically staged nonmetastatic squamous cell carcinoma of the esophagus received either radiotherapy alone (RT group) or concomitant radiotherapy and chemotherapy (RT + CT group) with curative intent. Each group originated at a different hospital, but all patients were irradiated in the same radiotherapy department. Chemotherapy consisted of cisplatin and 5-fluorouracil. Forty-two patients received RT alone, and 35 received RT + CT. Locoregional control, disease-free survival, and overall survival rates were compared. RESULTS: Locoregional control, disease-free survival, and overall survival rates were significantly higher in the RT + CT group when compared to RT group, 26% vs 5%, 20%, vs 2%, and 29% vs 7%, respectively, at 2 years (P = .01, 0.02 and 0.02, respectively). The median survival was 14 months for the RT + CT group and 7.5 months for the RT group. There was no difference in the incidence of distant metastases except for bone metastases. No one in the RT + CT group developed bone metastases compared to nine patients in the RT group (P = .01). CONCLUSION: This retrospective analysis shows improved locoregional control, disease-free survival, and survival when chemotherapy consisting of cisplatin and 5-FU is given in addition to radiation for patients with squamous cell carcinoma of the esophagus. Bony metastases were absent in those who received chemotherapy.

Prognostic significance of keratinization in nasopharyngeal carcinoma.

INTRODUCTION: Keratinization may be a vulnerable aid in predicting response to therapy for nasopharyngeal carcinoma. METHODS: The presence or absence of keratin in biopsy specimens was correlated with tumor behavior, locoregional control, patterns of failure, and survival of patients irradiated for nasopharyngeal carcinoma. RESULTS: Patients with keratinizing squamous-cell cancers (World Health Organization [WHO] type 1) had a higher incidence (76%) of locally advanced tumors than those with nonkeratinizing (WHO type 2) and undifferentiated (WHO type 3) cancers (55%). The former group of patients had a lower incidence (29%) of lymph node metastases than the later group (70%). Primary tumor was controlled in 62% and neck nodes were controlled in 82% of all patients. Primary tumor control rates were 29% in patients with keratinizing squamous-cell cancers and 79% in those with nonkeratinizing and undifferentiated cancers (P = .001). Nodal control rates were 76% for keratinizing squamous-cell cancer and 85% for nonkeratinizing and undifferentiated cancers (P = .001). The incidence of distant metastases was 6% in patients with keratinizing squamous-cell cancer and 33% in those with nonkeratinizing and undifferentiated cancers (P = .001). Patients with keratinizing squamous-cell cancers, even though they had a lower incidence of lymphatic and distant metastases, had a poorer survival rate because of a higher incidence of deaths from uncontrolled primary tumors and nodal metastases. The 5-year survival rates were 35% for all patients, 6% for those with keratinizing squamous-cell cancers, and 51% for nonkeratinizing and undifferentiated cancers respectively (P = .001). CONCLUSION: Higher doses of external beam radiotherapy with or without brachytherapy boost may be needed to improve local control and survival of patients with keratinizing squamous-cell carcinoma of the nasopharynx, whereas an effective systemic therapy is needed for nonkeratinizing and undifferentiated cancers, which tend to metastasize.

Beam attenuators and the risk of unrecognized large-fraction irradiation of critical tissues.

The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.

International comparison of postgraduate medical education in radiation oncology.

Despite variances in length, scope and content of postgraduate medical education in radiation oncology, there is a thread of commonality that runs through all programs. Aside from the emphasis on internal medicine in Canada and the emphasis on technical radiotherapy in the United States, it is surprising how little different content and duration of training are between the two countries. Similarly, there is movement to standardize training in radiation oncology in Europe that parallels the development of the European Community and the desire of physicians to cross borders.