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The effectiveness of the cough reflex in patients who aspirated following radiation for head and neck cancer was evaluated in 89 patients (49 chemoradiation, 33 postoperative radiation, and 7 radiation alone). All patients had modified barium swallow because of dysphagia. The cough reflex was graded as present and effective, ineffective, intermittently effective, or absent. All patients were cancer-free at the time of the swallowing study. The cough reflex was present and effective in 46 patients (52%), ineffective in 17 patients (19%), and absent in 26 patients (29%) on initial investigation. Among the 43 patients who had ineffective or absent cough reflex, their treatment was chemoradiation (26), postoperative radiation (13), and radiation alone (4). In 30 patients who had sequential modified barium swallow, the cough reflex was constantly effective, ineffective, or intermittently effective in 12 (40%), 13 (43%), and 5 (17%) patients, respectively. The cough reflex was frequently ineffective or absent in patients who aspirated following radiation for head and neck cancer. Cough may also be intermittently ineffective to protect the airways following radiation.

Purpose The aim of this study was to assess the survival, pattern of failure, morbidity, and prognostic factors of concurrent chemoradiation for locally advanced oropharyngeal cancer. Materials and methods A retrospective survey of patients who underwent chemotherapy and radiation for locally advanced oropharyngeal carcinoma at the Veteran Affairs North Texas Health Care System, Dallas, Tex. Results Between December 1999 and September 2004, 48 patients with locally advanced oropharyngeal cancer underwent concurrent chemotherapy and radiation. At a median follow-up of 23 months, the 3- and 5-year survival for the whole group were, respectively, 52% and 41%. Seventeen patients (35%) developed recurrences. There were 12 (25%) locoregional failures (6 local failures alone and 6 local and regional failures). Distant metastases developed in 8 patients (5 alone, 3 associated with locoregional failures). Four patients (8%) developed second primaries. No difference was observed in survival between base of tongue and tonsillar carcinoma (P = .32). The 5-year survival for T1-T2 and T3-T4 tumors was, respectively, 84% and 27% (P = .01). No patient with T1-T2 tumors developed distant metastases (P = .04). Forty-five patients (94%) developed toxicity grade 3 to 4 (40 mucositis and 26 hematological). The median weight loss was 18 lb (range, 0–47 lb). Eight patients (16%) developed aspiration pneumonia during and after treatment. Five patients (10%) died of aspiration (2 during and 3 post treatment). Four patients (8%) developed esophageal strictures requiring repeated dilatations post treatment. Two patients had radionecrosis (1 soft tissue and 1 bone) requiring hyperbaric oxygen. Eighteen patients (37%) had prolonged tube feedings (>3 months) after treatments because of severe dysphagia or aspiration. Conclusion Concurrent chemoradiation provided good locoregional control for locally advanced oropharyngeal carcinoma. Patients with small tumors (T1-T2) had excellent survival. The poor prognosis associated with large tumors may be due to the risk of developing distant metastases. Acute and late toxicities remained significant. Aspiration pneumonia and severe dysphagia were the most prevalent complications of the combined modality approach.

Background: To evaluate the impact of chemoradiation and postoperative radiation on patients’ quality of life (QOL) in a single institution. Methods: A retrospective analysis of 101 patients who had treatment for locally advanced head and neck cancer in a single institution. Forty-seven patients had chemotherapy and radiation, 54 patients underwent postoperative radiation. QOL was assessed with the University of Washington (UW), and the Hospital Anxiety (HA) and Depression (HD) questionnaires. All patients were free of disease at the survey time. Results: Mean and median UW scores were not different between the 2 groups: chemoradiation (65/67), postoperative radiation (62/63). Mean and median HA scores were 7.6/7 (chemoradiation), and 8.3/8 (postoperative radiation). Mean and median HD scores were 6.7/7 (chemoradiation), and 7.1/7 (postoperative radiation). Forty-four patients developed complications, with mean/median UW, HA, and HD scores of 55/55, 9.9/8, and 8.9/9, respectively. These scores were significantly different compared to the 57 patients without complications: 70/70 (p = 0.0001), 6.5/6 (p = 0.001), and 8.9/9 (p = 0.0001). Conclusion: There was no significant difference in QOL between chemoradiation and postoperative radiation in this retrospective study with a relatively short follow-up in the chemoradiation group. In addition, there were more patients with resectable disease in the postoperative group which may explain the lack of difference in QOL between the two groups. Patients who developed complications following treatment experienced lower QOL, more anxiety and depression. Our study raised the need to conduct a prospective randomized study to assess the real impact of chemoradiation and postoperative radiation on patients’ QOL.

Background and purpose We would like to assess the prevalence of aspiration before and following chemoradiation for head and neck cancer. Patients and methods We reviewed retrospectively the Modified Barium Swallow (MBS) in 63 patients who underwent concurrent chemotherapy and radiation for head and neck cancer. MBS was performed prior to treatment to determine the need for immediate gastrostomy tube placement. MBS was repeated following treatment to assess the safety of oral feeding prior to removal of tube feeding. All patients were cancer free at the time of the swallowing study. No patient had surgery. Dysphagia severity was graded on a scale of 1–7. Tube feedings were continued if patients were diagnosed to have severe aspiration (grade 6–7) or continued weight loss. Patients with abnormal swallow (grade 3–7) received swallowing therapy following MBS. Results Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8 grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a median follow-up of 2 months (1–10 months), one patient had grade 1, eight patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13 patients had grade 5, seven patients had grade 6, and 11 patients had grade 7. Six patients died from aspiration pneumonia (one before, three during, and two post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who had severe aspiration at diagnosis and the six patients who died from pneumonia, the prevalence of severe aspiration was 33% (21/63). Conclusions Aspiration remained a significant morbidity following chemoradiation for head and neck cancer. Its prevalence is underreported in the literature because of its often silent nature. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, and for rehabilitation.

Purpose: To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death. Experimental Design: Patients (N = 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter. Results: The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P = 0.032), history of surgery (P = 0.057), and those with poor performance status (P = 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P = 0.03), performance status > 1 (P = 0.001), treatment with chemotherapy (P = 0.01), the presence of metastatic liver disease (P = 0.03), higher d-dimer (P = 0.001), and thrombin antithrombin complex levels (P = 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P = 0.01) and d-dimer levels (P = 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in d-dimer (P = 0.001) and antithrombin (P = 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in d-dimer (P = 0.001), antithrombin (P = 0.001), and prothrombin fragment F1 + 2 (P = 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy. Conclusions: Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.

Warfarin-induced skin necrosis is a rare complication of anticoagulant treatment. The incidence of this complication is undetermined, but it has been estimated to occur between 1:100 and 1:10,000 of patients treated with anticoagulants. Coumarin skin necrosis occurs almost exclusively in patients with venous thrombosis between the 3rd and 10th day after beginning anticoagulation. Although protein C deficiency is the most common underlying hypercoagulable state reportedly associated with warfarin skin necrosis, very few cases have been linked to congenital protein S deficiency. This article addresses the association of hereditary protein S deficiency and warfarin skin necrosis, and provides suggestions for management.

The authors examined the efficacy of 2-chlorodeoxyadenosine (2-CDA) in the treatment of refractory inhibitors to factor VIII in persons without hemophilia. The drug was administered to 6 patients at a dose of 0.1 mg/kg as a 24-hour continuous infusion for a total of 7 days each cycle. An average of 3 immunosuppressive regimens per patient had been administered prior to enrollment in this study. The median inhibitor titer against human and porcine factor VIII before treatment with 2-CDA was 31 Bethesda units (BUs) and 9 BU, respectively. The median inhibitor titer against human and porcine factor VIII after treatment was 3.5 BU and 1.5 BU, respectively. The median time to reach nadir inhibitor titer in this study was 137 days, whereas the median time to reach a 50% increase in factor VIII was 117 days. No major toxicity was observed in any patient in this study. Patients with acquired inhibitors to factor VIII refractory to conventional immunosuppressive therapy may respond favorably to 2-CDA.

Platinum-based chemotherapy has been reported to induce diabetes and hyperosmolar coma in nondiabetic patients. The aim of the present study was to determine whether the administration of chemoradiation for head and neck carcinoma alters glucose metabolism during and after treatment. PATIENTS AND METHODS: Weekly nonfasting serum glucose level was obtained during treatment of one hundred and six patients with locally advanced head and neck cancer who underwent chemoradiationt. RESULTS: For the 91 non-diabetic patients, mean serum glucose level measured 97.75 before and 102.1, 102, 104.1, 109.1, 109.7, 110.3, 109.8, 113.2, 107.7 and 104.3 mg/dl during weeks 1-10 of treatment respectively. Serum glucose level elevation reached statistical significance for weeks 5-8. CONCLUSION: Chemoradiation for head and neck cancer may produce severe glucose metabolism alteration during treatment.

The aim was to assess the influence of treatment, tumor stages and sites on the severity of dysphagia following treatment. Sequential modified barium swallow (MBS) examinations were performed in patients who complained of chronic dysphagia following treatment of their head and neck cancer. Patients were selected if they were cancer free at their last MBS and had 2 or more MBS studies. Dysphagia severity was graded on a scale of 1 to 7. Dysphagia grade was compared between the first and last MBS to assess its evolution. Between 1996 and 2005, 63 patients with chronic dysphagia underwent MBS to assess dysphagia severity for nutritional support. Twenty-one patients (33%) had improvement of their dysphagia. Two of these patients (3%) achieved normalization of the swallowing. Twenty-five patients (40%) had no change of the dysphagia severity. Dysphagia grade increased in 17 patients (27%). Analysis of patient characteristics did not show any significant difference between these three groups of patients. MBS is a useful tool to monitor dysphagia severity and to identify aspiration risk. Stages of disease and treatment modality do not seem to impact on the course of dysphagia.

Our aim was to identify risk factors for aspiration following concurrent chemoradiation for oropharyngeal cancer. 46 patients with locally advanced oropharyngeal carcinoma underwent concurrent chemoradiation at our institution. All patients underwent modified barium swallow to assess dysphagia severity and to determine the need for continued tube feedings after treatment. Dysphagia severity was graded as 1-7. There were 5 Grade 2, 11 Grade 3, 5 Grade 4, 5 Grade 5, 10 Grade 6 and 10 Grade 7 scores. 25 patients (54%) developed aspiration (5 trace, 20 severe). The aspiration rate for T1-T2 and T3-T4 tumours was 31% and 67%, respectively (p = 0.03). There was no statistical difference in the aspiration rate between the base of the tongue and tonsillar carcinoma (p = 0.23). Despite anatomical organ preservation, most patients with locally advanced oropharyngeal carcinoma had moderate to severe dysphagia after chemoradiation. Patients with large tumours had a significant risk of developing aspiration following treatment.

The aim of the study was to assess the aspiration risk following postoperative radiation for head and neck cancer. Thirty-seven patients had Modified Barium Swallow before and following treatment. Dysphagia severity was graded from 1 to 7. Before treatment there were sixteen grade 1, seventeen grade 2, three grade 3 and one grade 5. Following postoperative radiation, two patients had grade 1, eleven patients had grade 2, thirteen patients had grade 3, four patients had grade 4, four patients had grade 5, one patients had grade 6, and two patients had grade 7. Nineteen percent (7/37) of the patients developed aspiration (grade 5-7). Aspiration is life-threatening and may develop for all tumor sites and stages.

Our aim was to assess the influence of age, co-morbidity factors and tumour characteristics on dysphagia severity in the diagnosis of head and neck cancer. Modified barium swallow (MBS) examinations were performed in patients at diagnosis of head and neck cancer. Dysphagia was graded on a scale of 1 to 7 of increasing severity. Between 2000 and 2006, 236 patients with dysphagia underwent MBS at diagnosis of their head and neck cancer. 82 patients were scored as Grade 1, 88 as Grade 2, 29 as Grade 3, 15 as Grade 4, 9 as Grade 5, 5 as Grade 6, and 8 as Grade 7. Grade 3-7 dysphagia occurred in 20% and 31% of patients with T1-T2 and T3-T4 tumours, respectively (p = 0.004). Corresponding values for N0-N1 and N2-N3 tumours were 20% and 39%, respectively (p = 0.002). The percentage of patients with Grade 3-7 dysphagia was 5%, 29%, 33% and 52% for oral cavity, laryngeal, oropharyngeal and hypopharyngeal tumours, respectively, (p = 0.002). Age and co-morbidity factors (e.g. diabetes, hypertension, coronary artery disease, peripheral vascular diseases and arthritis) did not appear to have an impact on swallowing in this limited retrospective study. Patients with locally advanced stages (T3-T4, N2-N3) are at risk of severe dysphagia. Patients with oral cavity tumours appear to be less at risk of dysphagia than those with tumours in different anatomic locations. The role of age and co-morbidity factors should be investigated in future prospective studies.

The aim of the present study was to assess dysphagia severity following postoperative radiation for locally advanced oropharyngeal cancer.Eighteen patients with oropharyngeal carcinoma had undergone postoperative radiation. There were eight base of tongue, eight tonsils, and two soft palate carcinomas. All the patients had undergone modified barium swallow (MBS) to assess the persistence of dysphagia (more than one month) post-treatment. All the patients were cancer-free at the time of the swallowing study. Dysphagia severity was graded as 1-7.At a median follow-up of 12 months, there were three grade 2, four grade 3, two grade 4, five grade 5, two grade 6, and two grade 7. Only three patients (17%) had normal swallow post-treatment. Six patients (33%) had mild to moderate dysphagia (grade 3-4). Nine patients (50%) developed aspiration (grade 5-7). Among the patients who developed aspiration, four (22%) required tube feeding for severe aspiration.Long-term (more than one year) dysphagia following postoperative radiation for oropharyngeal cancer may be symptomatic of permanent damage to the swallowing mechanism. Evaluation of patients who complain of persistence of dysphagia a year or more following treatment should include MBS, because of the increased risk of aspiration.

Treatment of patients with angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) often constitutes a challenge for the clinical haematologist. Single-agent and combination chemotherapy have failed to increase the response rate or survival of patients with AILD. A total of seven patients with refractory or relapsed AILD were treated with 2-chlorodeoxyadenosine (2-CdA) for variable number of cycles. The overall response rate was 57% with two patients (28.5%) achieving complete and sustained response. 2-Chlorodeoxyadenosine appears to be an active agent for patients with previously treated AILD. Phase II studies evaluating the efficacy of this agent as front-line treatment for AILD are justified, especially in the absence of any effective therapy for this disorder.

To assess the risk of developing aspiration during chemoradiation for head and neck cancer.A retrospective review of 114 patients who underwent concurrent chemoradiation for locally advanced head and neck cancer was undertaken. Patients were determined as having aspiration if they had pneumonia on chest-X-ray (CXR) and/or had documented aspiration on the modified barium swallow (MBS) during their treatment.Fifteen patients (13%) developed aspiration during chemoradiation. Twelve patients (10%) had aspiration demonstrated on CXR alone (9 patients) or combined with MBS (3 patients). Three patients (3%) had aspiration on MBS alone. Three of the six patients with aspiration observed on MBS had normal swallowing on their pretreatment MBS. All 15 patients had severe mucositis and neutropenia at the time of the aspiration. Despite broad-spectrum antibiotics and supportive care, six patients (5%) died.Aspiration may develop during chemoradiation for head and neck cancer because of radiation-induced altered swallow.

Summary Background We would like to assess the safety and effectiveness of prophylactic percutaneous endoscopic gastrostomy (PEG) tube feedings during concurrent chemoradiation for head and neck cancer. Methods Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. All patients underwent PEG tube placement prior to the treatment because of the expected mucositis. Gastrostomy tubes were removed following treatment when the patients were able to resume oral feedings without aspiration. Results Between March 1999 and 2006, 104 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. One patient declined placement of gastrostomy tube. Ninety patients (86%) developed grade 3–4 mucositis during chemoradiation. Five patients died during treatment from aspiration pneumonia and sepsis. One hundred two patients lost weight during treatment. The mean and median weight loss during concurrent therapy was, respectively, 8.5 and 8 kg (1–23.5 kg). Following treatment, tube feedings were continued 1–41 months (mean: 8 months; median: 5 months) because of continued weight loss, chronic dysphagia, or aspiration. At a median follow-up of 19 months (1–62 months), no patient developed serious complications from tube feedings. Conclusion Dysphagia resulting from the severe mucositis produced severe weight loss, despite tube feedings. Gastrostomy tube feedings are safe. Gastrostomy tubes should be placed prophylactically for patients undergoing chemoradiation for head and neck cancer.

The aim of this study was to evaluate the aspiration rate following nonsurgical therapy, i.e. chemoradiation or radiation alone for laryngeal cancer. Modified barium swallow was performed in 43 patients who complained of dysphagia following chemoradiation (n = 22) or radiation alone (n = 21) for laryngeal cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1–7. Patients were grouped according to the dysphagia severity: no aspiration (grade 1–4), and severe (grade 5–7). Mean and median dysphagia grades were 4.4/5 and 3.5/3 for chemoradiation and radiation, respectively. Aspiration occurred in 12 patients (54%) of the chemoradiation group and 7 (33%) of the radiation alone group (p = 0.13). There was a higher proportion of patients with large tumor (T3–T4) in the chemoradiation group (64%) compared to the radiation group (5%) (p = 0.0001). Aspiration is a significant source of morbidity in patients treated for laryngeal cancer with chemoradiation or radiation alone. Aspiration occurred in both groups. Although the observed difference in aspiration rates did not achieve statistical significance, the higher aspiration rate in the chemoradiation group may be due to a higher proportion of large tumors, to the additional toxic effect of chemotherapy, or to the small number of patients in both groups. Diagnostic studies such as modified barium swallow should be part of future laryngeal cancer prospective studies to assess the prevalence of aspiration as it may be silent.

This study examines the efficacy of swallowing therapy in cancer-free patients who developed aspiration following treatment for locally advanced head and neck cancer. The records of 41 patients who underwent swallowing therapy for aspiration were reviewed. All patients were cancer free at a median follow-up of 25 months (6-150 months). Their treatment were respectively chemoradiation (24), and postoperative radiation (17). All patients had two or more modified barium swallow (MBS). Dysphagia severity was graded from 1 to 7. Dysphagia grade was compared before and following swallowing therapy. Before swallowing therapy, there were 16 grade 5 (trace aspiration), and 25 grade 6-7 (severe aspiration). In the chemoradiation group, there were nine grade 5, five grade 6, and 10 grade 7. Corresponding numbers for the postoperative group were: seven grade 5, seven grade 6, and three grade 7. Following swallowing therapy, there were six grade 3, seven grade 4, 10 grade 5, six grade 6, and 12 grade 7. In the chemoradiation group, there were four grade 3, three grade 4, four grade 5, five grade 6, and eight grade 7. In the postoperative group, there were two grade 3, four grade 4, six grade 5, one grade 6, and four grade 7. Overall, 13 patients (32%) had improvement of their dysphagia severity. Seven of them were in the chemoradiation group (29%), and six (35%) were in the postoperative group. Among 25 patients who presented with grade 6-7 aspiration, only nine (36%) improved to grade 5 or less. Four of them (27%) were in the chemoradiation group, and five (29%) were in the postoperative group. Swallowing therapy is effective to improve dysphagia severity and reduce the need for tube feedings. However, a significant number of patients still suffered from chronic severe aspiration. New strategies must be devised to improve their outcome.

Objective The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. Materials and methods We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1–7. Patients were grouped according to the dysphagia severity: mild (grades 2–3), moderate (grades 4–5), and severe (grades 6–7). Results Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant ( p = 0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant ( p = 0.29). There was a higher proportion of patients with large tumor (T3–T4) in the chemoradiation group who developed severe dysphagia. Conclusion Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent.

We would like to assess the evolution of chronic dysphagia (1 year or more) following treatment for head and neck cancer. Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. Each patient had at least 2 MBS. Severity of dysphagia was compared between the first and last MBS study to determine whether the swallowing dysfunction had returned to normal. Patients with complaint of dysphagia and normal MBS also underwent a regular barium swallow to assess the structural integrity of the pharynx and esophagus. Between 1996 and 2001, 25 patients with dysphagia underwent repeat MBS following treatment. Swallowing dysfunction did not return to normal in the majority of the patients. At a median time of 26 months following treatment (range 15-82 months), only two patient (8%) had normalization of the swallowing. The severity of dysphagia decreased in eight patients (32%), remained unchanged in 12 patients (48%), and worsened in five patients (20%). Eight patients (32%) still had aspiration problems at 12-83 months following treatment. Six patients (24%) required dilation because of pharyngeal stenosis. Three patients who required dilation had improvement of the dysphagia severity. Chronic dysphagia is a relentless process possibly due to excessive scarring. Patients with chronic dysphagia are at risk of malnutrition, and aspiration. Management of chronic dysphagia requires a team approach with nutritional support, psychological counseling, dilation, and tube feedings when indicated.

The purpose of this investigation was to evaluate chronic dysphagia (lasting 3 or more months) following treatment for head and neck cancer. Since dysphagia is a common sequela post therapy in cancer survivors, it may be helpful for the clinician to be aware of the persistence of dysphagia as well as its usual severity. Modified Barium Swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1 to 7. Each patient had sequential MBS and underwent swallowing therapy in between. The severity of dysphagia was compared between the first and last MBS study to determine whether the swallowing function had returned to normal.Between 1996 and 2004, 12 patients with dysphagia underwent repeated MBS following treatment. Swallowing function did not return to normal in all patients. At a median time of 29 months following treatment (range 8 to 94 months), the severity of dysphagia decreased in 8 patients (67%), remained unchanged in 3 patients (25%) and worsened in 1 patient (8%). Chronic dysphagia following treatment is unlikely to resolve with time despite rehabilitation therapy. Excessive scarring following treatment may be responsible for the persistence and severity of dysphagia. Physicians should be aware of the long-term effects of dysphagia on patient nutrition and psychological well-being.

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 x 10(9)/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 microg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 microg/kg and the median number of doses administered was 5 (range, 3-10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 microg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.

Background To assess the prevalence, severity and morbidity of dysphagia following concurrent chemoradiation for head and neck cancer. Patients and methods Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. Modified barium swallow (MBS) studies were performed if the patients complained of dysphagia or if there was clinical suspicion of aspiration. The severity of dysphagia was graded on a scale of 1–7. If significant abnormalities were found, swallowing studies were repeated until resolution of dysphagia. Results Between March 1999 and May 2002, 55 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. Aspiration pneumonia was observed in eight patients, three during treatment and five following treatment. Five patients died from pneumonia. Two patients developed respiratory failure requiring intubation as a complication of pneumonia. At a median follow-up of 17 months (range 6–48 months), 25 patients (45%) developed severe dysphagia requiring prolonged tube feedings for more than 3 months (22 patients) or repeated dilatations (three patients). Among 33 patients who underwent MBS following treatment, 12 patients (36%) had silent aspiration (grade 6–7 dysphagia). Thirteen patients (39%) developed grade 4–5 dysphagia which required prolonged enteral nutritional support to supplement their oral intake. Most patients had severe weight loss (0–21 kg) during treatment, likely due in part to mucositis in the orodigestive tube. Conclusions Dysphagia is a common, debilitating and potentially life-threatening sequela of concurrent chemoradiation for head and neck malignancy. Physicians should be aware that the clinical manifestations of aspiration may be unreliable and insidious, because of the depressed cough reflex. Modified and traditional barium swallows should be performed following treatment to assess the safety of oral feeding and the structural integrity of the pharynx and esophagus. Patients with severe dysphagia may benefit from rehabilitation. Tube feeding should be continued for those with aspiration.

Purpose To evaluate the quality of life (QOL) associated with dysphagia after head-and-neck cancer treatment. Methods and materials Of a total population of 104, a retrospective analysis of 73 patients who complained of dysphagia after primary radiotherapy (RT), chemoradiotherapy, and postoperative RT for head-and-neck malignancies were evaluated. All patients underwent a modified barium swallow examination to assess the severity of dysphagia, graded on a scale of 1–7. QOL was evaluated by the University of Washington (UW) and Hospital Anxiety and Depression questionnaires. The QOL scores obtained were compared with those from the 31 patients who were free of dysphagia after treatment. The QOL scores were also graded according to the dysphagia severity. Results The UW and Hospital Anxiety and Depression scores were reduced and elevated, respectively, in the dysphagia group compared with the no dysphagia group ( p = 0.0005). The UW scores were also substantially lower among patients with moderate-to-severe (Grade 4–7) compared with no or mild (Grade 2–3) dysphagia ( p = 0.0005). The corresponding Hospital Anxiety ( p = 0.005) and Depression ( p = 0.0001) scores were also greater for the moderate-to-severe group. The UW QOL subscale scores showed a statistically significant decrease for swallowing ( p = 0.00005), speech ( p = 0.0005), recreation/entertainment ( p = 0.0005), disfigurement ( p = 0.0006), activity ( p = 0.005), eating ( p = 0.002), shoulder disability ( p = 0.006), and pain ( p = 0.004). Conclusion Dysphagia is a significant morbidity of head-and-neck cancer treatment, and the severity of dysphagia correlated with a compromised QOL, anxiety, and depression. Patients with moderate-to-severe dysphagia require a team approach involving nutritional support, physical therapy, speech rehabilitation, pain management, and psychological counseling.

Concurrent chemotherapy and radiation are usually indicated for locally advanced carcinomas such as head and neck and anal malignancies. Because of the toxicity of the treatment, patient selection plays an important role in recommendations to treat with a curative intent. Elderly patients (70 years), those with underlying medical conditions or acquired immunological disorders (AIDS) are commonly excluded from combined modality therapy because of their perceived inability to tolerate the aggressive treatment. They may thus be deprived of a potentially curative therapy. In an attempt to improve outcome, we conducted a pilot study using amifostine, a radioprotector, to increase the tolerance of such compromised individuals to treatment. Amifostine (500 mg intravenously) was given during chemotherapy on days 1-5, and days 21-25 of radiation regimen. All patients were able to complete the chemoradiation. Despite the locally advanced stage of the disease, five out of our six patients achieved a complete response (CR). One patient with synchronous primaries had a complete response for the base of tongue cancer and regression of the esophageal cancer, which allowed him to resume oral feeding. All patients achieved improved quality of life. Successful chemoradiation appears to be feasible in patients with advanced stage, age and/or underlying medical conditions when amifostine is integrated in the treatment.

Locally advanced non-small cell lung carcinoma (NSCLC) has a poor prognosis when treated with conventional chemotherapy and radiation. New chemotherapy agents like paclitaxel may increase the sensitivity of tumors cells to radiation and potentially improve the outcome. The optimal combination of taxane-based chemotherapy agents and radiation is still unclear. We investigated the feasibility of induction chemotherapy followed by concurrent near systemic dose of chemotherapy with radiation. A prospective survey of 29 previously untreated patients with unresectable stage III (15 IIIA, 14 IIIB) NSCLC treated with paclitaxel and carboplatin in combination with radiation was reviewed. The patients received 2 cycles of paclitaxel 225 mg/m2 intravenously (i.v.) over 3 hours, days 1, 22; carboplatin at area under the curve (AUC) 6 based on Calvert formula days 1, 22 following completion of the paclitaxel infusion. Following induction chemotherapy, radiation therapy started on day 43 until completion to a tumor dose of at least 5960 cGy. Cycles 3 and 4 of chemotherapy were begun on days 43 and 63, respectively, and consisted of paclitaxel 175 mg/m2 i.v. over 3 hours, and carboplatin at AUC 6 following paclitaxel infusion. The response rate, acute toxicity, long-term complications, pattern of failure and survival were evaluated and compared to previous studies in the literature. Two patients were lost to follow-up. The response rate to induction carboplatin/paclitaxel was 52%. An overall response rate (complete and partial responders) of 85% was obtained following chemotherapy and radiation. Grade 3-4 acute side-effects were recorded in 9 patients (31%) and consisted of esophagitis (8 patients) and anemia (1 patient). One patient died from cachexia 3 months following treatment (3.7%). The median survival and 3-year survival were 15 months and 30%, respectively, for the remaining 27 patients at a median follow-up of 11 months. There was no difference in survival between stages IIIA and IIIB at 2 years (IIIA: 22%, IIIB: 31%). Local or regional recurrences and distant metastases developed in 9 patients (33%) and 13 patients (46%), respectively. The combination of paclitaxel, carboplatin and radiation for locally advanced non-small cell carcinoma is feasible with acceptable toxicity. The response rate compares favorably with previously reported studies. The decrease of tumor volume following induction chemotherapy allows sparing of the lungs from the toxicity of radiation. However, grades 3-4 esophagitis remain significant. The addition of amifostine may be beneficial in this setting.

The purpose of this study was to determine the toxicity and efficacy of single daily fractionation as compared with twice-a-day radiation therapy in combination with chemotherapy for preoperative locally advanced thoracic esophageal carcinoma. A retrospective survey was done of 42 patients undergoing concurrent chemotherapy and radiation for preoperative locally advanced thoracic esophageal carcinoma. Twenty-five patients had 5-fluorouracil ([5-FU]), 1,000 mg/m2/d by continuous infusion, days 1-5, and days 22-26), cisplatin (100 mg/m2 intravenously, days 2 and 22), and radiation to a total dose of 4,500 to 5,040 cGy in 180 cGy/fraction every day. Seventeen patients received 5-FU (300 mg/m2/d by continuous infusion, days 1 and 21), cisplatin (20 mg/m2/d for 1 hour, days 1-5 and days 17-20), vinblastine (1 mg/m2 intravenously, days 1-5 and days 17-21) and accelerated hyperfractionated radiation 150 cGy twice a day to a total dose of 4,500 cGy. Response rate, survival, local regional failure rates, and treatment toxicity of the two groups were compared. Surgery was aborted in one patient and another patient refused surgery in the single daily-fractionation group. All patients underwent surgery in the twice-daily group. Complete response (CR) was noted in 12 patients (52%) in the single daily-fractionation group as compared with 9 patients (52%) in the twice-daily group. The median and 3-year survival were 20 months and 35%, respectively, in the single daily-fractionation group. Corresponding figures were 18 months and 32%, respectively, in the twice-daily group. For the 2 groups combined, a statistically significant improvement in survival was observed among blacks who achieved a CR (31 months) as compared with the ones with residual disease (13.5 months). Local and regional failures were 28% and 17%, respectively, for the single daily-fractionation and twice-daily groups. Distant metastases remained significant in both groups and were 36% (single daily-fractionation) and 41% (twice-daily), respectively. Grades III to IV esophagitis and hematologic toxicity developed in 36% and 64% of patients of the single daily-fractionation and twice-daily groups, respectively. The incidence of late complications was 16% (single daily-fractionation) and 11.7% (twice-daily). Preoperative chemotherapy and radiation is effective to achieve a high pathologic CR. Both radiation therapy fractionation schedules are comparable in efficacy and toxicity. Further investigations should be done to assess whether ethnicity may play a role in the prognosis of esophageal carcinoma.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are well recognized complications of cancer. However, our current knowledge of this association is derived from studies conducted more than a decade ago. In light of the changes in medical practice and the improvement in cancer care in recent years, a re-evaluation of the relationship between malignancy and venous thrombosis is in order. Of a total of 1041 patients with solid tumors admitted to 3 major medical centers, there were 81 (7.8%) diagnosed with DVT/PE. Patients were more likely to develop DVT/PE during chemotherapy (p = .0001). Advanced malignancies (p = .001), renal carcinoma (p = .005), pancreatic (p = .001), gastric (p = .014) and brain tumors (p = .001) were independent variables strongly associated with the occurrence of venous thrombosis. The occurrence of thrombotic events in the population tested in this study did not adversely affect survival (p = .082). The study identifies subset of patients with cancer at high risk for venous thrombosis. Early prophylaxis with anticoagulants in these patients may be warranted. Most importantly, further clinical trials are desperately awaited to detect possible new trends in the frequency and types of thrombotic events and to better define prevention strategies in cancer patients at risk for thrombosis. The association between venous thromboembolic disease (VTD) and malignant neoplastic disorders is well known and has been the subject of several reports for more than a century. There is a general agreement among investigators that thrombotic complications in patients with cancer occur at a rather high frequency, and that other circumstantial factors such as surgery or chemotherapy potentiates this risk. However, several important considerations pertaining to cancer and thrombosis continue to be shrouded in controversy. For example, there are inexplicable differences in the proportion of patients with cancer diagnosed with deep venous thrombosis (DVT) or pulmonary embolism (PE) reported in the literature. In the absence of large well-controlled studies, one may only postulate on the reasons that contributed to these differences. The inclusion of different types of VTD such as superficial, venous, arterial or vascular access device-induced thrombosis may have led to overestimation of the incidence of these events in patients with underlying malignancy. Another possible explanation for this discrepancy relates to the use of a variety of diagnostic and methodological criteria ranging from observation and clinical suspicion to more invasive procedures resulting in considerable differences in the rate of reported clotting events. Along the same line of discussion, one may argue whether VTD is a random event or constitutes a complication that occurs more commonly in patients with distinct characteristics and certain tumor types. To further investigate the association between malignancy and thrombosis, we evaluated 1041 patients with solid tumors for the risk of DVT/PE. The main objectives of the study were to determine the frequency of DVT/PE based on validated diagnostic criteria and to identify patients with cancer at high risk for developing these thrombotic episodes. Also, we evaluated the impact of VTD on the survival of these patients.

BACKGROUND The standard of care for locally advanced head and neck carcinoma usually has been surgery followed by radiation therapy. Patient survival using this approach has been reported to be poor. The disfiguration resulting from surgery and the long-term morbidity of postoperative radiation often results in considerable distress. Concurrent chemotherapy and radiation was introduced to improve outcome. Excellent local control and survival results often have been reported in Phase II and Phase III studies. The acute toxicity of combined chemotherapy and radiation is significant. However, organ preservation may improve quality of life. This review article summarizes the findings from published series of surgery, postoperative radiation, radiation therapy alone, and chemoradiation with regard to quality of life issues for patients with locally advanced head and neck carcinoma. METHODS A literature search was used to identify quality-of-life studies of postoperative radiation, radiation therapy alone, and chemoradiation in patients with locally advanced head and neck carcinoma. Factors affecting long-term quality-of-life issues in each treatment modality were identified, compared, and evaluated. RESULTS Speech disorder, dysphagia, pain, and depression were found to be the common side effects affecting quality of life regardless of the treatment modality. Xerostomia is the major complication affecting patients undergoing radiation or chemoradiation. CONCLUSIONS Acute side effects of combined chemotherapy and radiation therapy usually were found to resolve after treatment. Long-term morbidity is substantial because of xerostomia and severe dysphagia. However, preliminary studies suggest that because of organ preservation, patients may achieve a better quality of life after chemoradiation compared with the conventional use of surgery and postoperative radiation. Cancer 2002;94:1131–41. © 2002 American Cancer Society. DOI 10.1002/cncr.10257

BACKGROUND Chronic disseminated candidiasis (CDC) is a serious complication of treatment in patients with acute leukemia. Although some general risk factors are known to predispose to systemic fungal infections, few studies have addressed the relevance of certain clinical and laboratory features in patients with CDC. PATIENTS AND METHODS To define a subset of patients at high risk for CDC, the authors evaluated the demographics and clinical and laboratory characteristics of 423 patients with acute leukemia. Patients who had bone marrow transplant before the diagnosis of CDC were excluded from the analysis. The diagnosis of CDC was based on blood cultures, liver biopsy, and imaging studies. The authors conducted 2 separate regression analyses on 3 subsets of patients: patients without documented candidiasis (n = 374), patients with CDC (n = 23), and patients with candidemia (n = 26). RESULTS According to multivariate analysis, younger age (P = 0.009; odds ratio [OR], 1.96; 95% confidence interval [CI], 1.72–2.99), duration of neutropenia of 15 days or longer (P = 0.0003; OR, 11.7; 95% CI, 3.04–45.1), and use of prophylactic quinolone antibiotics (P = 0.039; OR, 3.85; 95% CI, 1.11–13.4) emerged as independent factors related to the development of CDC in patients with acute leukemia. The presence of severe mucositis, colonization with Candida, and administration of high-dose ara-C were statistically significant parameters in univariate analysis only (P = 0.0001, P = 0.003, and P = 0.058, respectively). CONCLUSIONS On the basis of the results of this investigation, it is possible to define a subset of patients with acute leukemia at very high risk for CDC. Because of the morbidity and mortality of this infection, a targeted prophylactic approach may be more effective and less costly than the random administration of antifungal agents. Cancer 2001;92:1349–53. © 2001 American Cancer Society.

Nguyen NP, Sallah S, Karlsson U, Vos P, Ludin A, Semer D, Tait D, Salehpour M, Jendrasiak G, Robiou C. for papillary serous carcinoma of the endometrium after surgical staging.Background: To investigate the pattern of failure and the prognosis following pathological staging for uterine papillary serous carcinoma (UPSC).Patients and methods: A retrospective review was conducted of 22 patients with UPSC, treated between 1989 and 1998 at a single institution. All patients were surgically staged. Two patients with advanced disease received chemotherapy only. Two patients with early-stage disease were followed without further treatment. Eighteen patients received postoperative irradiation; eight patients received whole abdominal irradiation (WART), and the remaining 10 patients, pelvic irradiation (PRT). In addition, seven of these patients received vaginal cuff irradiation with low-dose-rate or high-dose-rate brachytherapy. Toxicity, pattern of failure, and survival were evaluated and compared to the literature.Results: Seven patients (32%) developed distant metastases, three out of seven (42%) after WART. Four out of seven patients who had distant metastases died from disease progression during subsequent chemotherapy. All patients with distant metastases had locally advanced-stage disease at presentation (six stage III, one stage IV). Four patients with pelvic recurrences developed concurrent (2) and subsequent (2) distant metastases. Three patients had isolated distant metastases. No patient with early stage-disease (stage I and II) died from disease progression.Conclusion: Pathological staging should be performed for all patients with UPSC to determine the prognosis as well as to tailor the treatment. The role of abdominal irradiation in the treatment of UPSC is yet to be determined; however, such an approach may not be necessary for the control of disease for patients with early-stage (I and II) disease. Patients with locally advanced-stage (stage III) disease are at risk of local regional failures and distant metastases despite WART. Therefore, the benefit of WART for advanced-stage disease is also questionable. Paclitaxel-based chemotherapy is currently being investigated in this setting.

A case of recurrent and twice resected sinonasal melanoma is presented. The large recurrent tumor was found to regress by a concurrent combination of 6660 cGy photon radiation and subcutaneous interferon-alpha injections given for a period of 8 weeks. Possible mechanisms of potentiation between interferon and radiation are discussed. The unexpected result in this case report raises interesting questions about this treatment combination.

Background The occurrence of autoimmune hemolytic anemia (AIHA) in patients with non-Hodgkin's lymphoma (NHL) is well known. However, there is lack of information in the literature in terms of the significance and impact of such phenomenon on the clinical course of these patients. Patients and methods We analyzed the clinical and laboratory features, course and response of 16 patients with non-Hodgkin's lymphoma (NHL) and autoimmune hemolytic anemia (AIHA). Patients with small lymphocytic lymphoma and angioimmunoblastic lymphadenopathy with dysproteinemia were excluded from the analysis. The significance of certain parameters, such as cell type (B-vs. T-cell), stage of NHL and presence of serum monoclonal immunoglobulin were examined. The cohort consisted of 501 patients with NHL evaluated during the study period. Results The response rate for the group of patients with NHL/AIHA and for the cohort was 44% and 62%, respectively; P=0.0138. T-cell histology was overrepresented in the patients with AIHA/NHL (33% vs. 14% P=0.048). The occurrence of AIHA was not statistically significant among the four stages of NHL (P=0.722), while a significantly higher proportion of patients with AIHA had serum monoclonol gammopathy when compared to the cohort (25% vs. 8% P=0.03). The patients with NHL who did not develop AIHA had better overall survival and median survival compared to the NHL/AIHA group (P=0.006 and P=0.0001, respectively). Conclusions The study provides for the first time a descriptive clinicopathologic analysis of patients with AIHA and NHL. Certain pathologic and laboratory features were more likely to be associated with the occurrence of AIHA in patients with NHL. Most importantly, was the adverse impact of AIHA on the survival of patients with NHL. Therefore, this finding should be taken in consideration when risk-stratifying patients with NHL.

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.

Objective.—To evaluate the occurrence of megaloblastic anemia induced by the infusion of therapeutic or prophylactic methotrexate in patients with acute leukemia. Design.—Data on 3 patients with acute leukemia receiving intrathecal methotrexate were prospectively analyzed. Setting.—Large tertiary-care center. Results.—All 3 patients with acute leukemia developed megaloblastic anemia confirmed by examination of the bone marrow aspirate and biopsy. Two of the 3 patients had low folic acid levels, while all patients had normal serum B12 levels. All patients responded favorably to a therapeutic trial of folic acid. The median time for recovery of the hematologic parameters in these patients was 7 days. Conclusions.—Intrathecally administered methotrexate may result in megaloblastic changes in the bone marrow of leukemic patients. The morphologic clues suggestive of folate deficiency in patients with acute leukemia may be masked by coexisting factors, such as the effects of cytotoxic treatment, prior transfusions, or persistent changes from the leukemic clone itself. Caution should be exercised to avoid attributing these changes to the neoplastic process, since the prognosis and treatment for the conditions involved are totally different. Repeat examination of the bone marrow, obtaining folic acid and vitamin B12 levels, and a therapeutic trial of folic acid may help identify and reverse these changes.

Hepatosplenic candidiasis (HSC) is a morbid complication encountered in immunocompromised individuals, especially, those being treated with intensive chemotherapy protocols for acute leukemia. Immediate recognition of this complication and initiation of appropriate treatment is crucial in order to control the infection, decrease the morbidity and mortality, and avoid delays in treatment of the underlying condition. The definitive diagnosis requires either positive blood cultures for yeasts in the presence of abnormal findings on imaging studies consistent with HSC, or liver biopsy demonstrating yeast forms or pseudohyphae. We describe our experience in the evaluation of 15 patients with HSC using magnetic resonance imaging (MRI) as a diagnostic and follow-up tool. The diagnosis of HSC was established by liver biopsy in 11 patients (73%), and by positive blood cultures for Candida in 4 patients (27%). All patients had MRI findings consistent with HSC during the study period. Amphotericin B was administered intravenously to all 15 patients (median duration of treatment, 62 days). Repeat MR images were obtained at 2 weeks, 6 weeks and then at monthly intervals until the resolution of abnormalities. The median time for the disappearance of MRI lesions was 9 weeks. Alterations in the appearance of lesions on MRI were noted throughout chemotherapy in all the 13 (86.6%) responding patients. Our results suggest that MRI when used in patients with high clinical suspicion for HSC provide an alternative for liver biopsy or other invasive diagnostic procedures and that appropriate response to treatment can be safely monitored by obtaining sequential MRI studies.

A 61-year-old male with Epstein syndrome and chronic renal failure was admitted to our institution for kidney transplantation. He was asymptomatic at the time of evaluation. Physical examination revealed pallor and marked splenomegaly measuring approximately 12 x 10 cm below the left costal margin. Because of this finding, and a history of resected non-small lung cancer, a CT scan of the abdomen was obtained. This demonstrated massive, diffusely nodular splenomegaly. This article describes the histopathologic and immunohistochemical findings of littoral cell angioma, a novel splenic tumor. Also, we discuss the differential diagnosis and include a description of the imaging study performed. To our knowledge, this is the first case report of littoral cell angioma occurring in a patient with Epstein syndrome, and the first radiographic appearance of this rare tumor.