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Objectives We assessed the severity of dysphagia before and after oral cavity cancer surgery.

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.

Concurrent chemoradiation offers excellent local control and survival for patients with locally advanced head and neck cancer while allowing anatomic organ preservation. Treatment toxicity is significant, however, often resulting in long-term dysphagia and aspiration. We review the prevalence of post-treatment swallowing dysfunction, describe current thinking about its pathogenesis and management, and signal possible directions for future research.Apoptosis from chemoradiation induces abnormal motility of the upper aerodigestive tract, resulting in stasis of the bolus in all phases of the swallow, and resulting in aspiration when the larynx is not protected during swallow. Long-term scarring may result in stenosis of the upper digestive tract. Recent findings suggest the role of transforming growth factor beta 1 in the pathogenesis of normal tissue damage and late scarring induced by radiation. Aspiration is often silent, and therefore a modified barium swallow or videofluoroscopy are required for its diagnosis. Swallowing therapy may improve swallowing efficiency and reduce the aspiration rate, and should be started immediately.Successful management of swallowing dysfunction following chemoradiation is a complex undertaking requiring a team approach. Collaboration among different specialists (physicians, speech pathologist, dietitian, and psychologists) remains the key to a desirable outcome.

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.

Radiation enteritis is one of the most feared complications of abdominal and pelvic radiation. Once its occurs, the process is relentless and may result in the patient's death. Available treatment is only supportive. Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis. New treatment modalities may be devised to improve the outcome of patients who are affected with this complication.A literature search was used to identify the common denominator between many radiation-induced fibrotic conditions and other sclerotic diseases. Factors that affect the disease process and possible therapeutic interventions were evaluated.The hyperstimulation of transforming growth factor beta1 (TGF-beta1) leads to increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN-gamma) inhibits the effects of TGF-beta1 in the nucleus. The fibrotic process may be reverted by IFN-gamma in various pathologic conditions.Radiation enteritis and other radiation-induced, long-term complications are characterized by excessive stimulation of TGF-beta1. Preliminary studies suggest that IFN-gamma may be effective in the treatment of patients with radiation-induced cutaneous fibrosis. IFN-gamma should be considered in Phase I-II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis.

SummaryDeep 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 (1–8). 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 (9,10). 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 (2, 4, 5, 11). 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 (12). 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 spontaneous formation of neutralizing antibodies (inhibitors) to factor VIII (FVIII) in patients with cancer is a well known phenomenon. However, to the authors' knowledge there is lack of information in the literature with respect to the clinical course of these patients and the nature of the association between malignant tumors and acquired hemophilia. METHODS A retrospective study of 41 patients with cancer and acquired hemophilia was conducted. The patients were identified through a MEDLINE search between 1974–2000. All patients had detailed clinical and laboratory information available and descriptions of the course of the inhibitor in relation to cancer treatment. The patients were divided into two groups: responders and nonresponders. The stage of the tumor, inhibitor titer, FVIII level, and survival data were examined and compared between the two groups. RESULTS A total of 63 hemorrhagic episodes were reported in 25 patients with solid tumors and 16 patients with hematologic malignancies. The median inhibitor titer at the time of the diagnosis of acquired hemophilia was 14 Bethesda units (BU) (range, 1–435 BU). The complete response (CR) rate to treatment of the inhibitor was 70% and patients who achieved a CR were more likely to have early stage tumors (P = 0.0007) and a lower median inhibitor titer at the time of presentation compared with nonresponders (12 BU vs. 78 BU; P = 0.007). The overall survival was significantly higher in patients who achieved a CR compared with patients with a persistent inhibitor (75% vs. 17%; P = 0.0006). CONCLUSIONS Although it remains an uncommon occurrence, the development of inhibitors to FVIII should be considered as a cause of bleeding in some patients with malignant diseases. Because of the high response rate and the impact of this type of hemorrhage on cancer patients, efforts should be directed toward immunosuppression of the inhibitor in a fashion similar to that used in other patients with acquired hemophilia. To our knowledge the link between malignancy and the formation of antibodies to FVIII is unclear; however, it appears that treatment of cancer with chemotherapy or surgery may accelerate the eradication of the inhibitor in some patients. Long term prospective studies are needed to better assess the association between cancer and acquired hemophilia. Cancer 2001;91:1067–74. © 2001 American Cancer Society.

SummaryDisseminated intravascular coagulation (DIC) is a well known hemostatic complication of solid tumors. We evaluated the occurrence of DIC in 1117 patients with solid tumors. Of these patients, 76 (6.8%) were diagnosed with DIC. There were a total of 145 bleeding and clotting episodes reported in the 76 patients. Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen degradation products were the most common coagulation abnormalities encountered in patients with DIC. In multivariate analysis, older age (p = .0001), male gender (p = .009), advanced malignancies (p = .027), breast cancer (p = .038) and the presence of necrosis in the tumor specimen (p = .004), emerged as independent factors significantly related to the occurrence of DIC in patients with solid tumors. Of the 76 patients, 25 (33%) achieved response to treatment of DIC as defined in the study. Patients with early stage and advanced malignancies who developed DIC had inferior survival when compared with their counterparts without DIC (p = .039 and p = .005, respectively). Taken together, this study indicates that certain clinical and laboratory features are more common in patients with solid tumors who developed DIC. The occurrence of DIC appears to have an independent effect on survival of patients with cancer. Cooperative studies are encouraged to better address the usefulness and optimal prophylactic heparin regimen in patients at risk for DIC.

A retrospective study of 23 patients with acute leukaemia and hepatosplenic candidiasis (HSC) was conducted to evaluate clinical treatment characteristics in terms of amount and duration of antifungal agents and to assess treatment outcome. Patients were admitted to two major tertiary care centres between 1990 and 1998. The diagnosis of HSC was based on clinical, blood cultures, histologic and imaging studies. Patients were treated with amphotericin B without interruption of the planned chemotherapy regimens. Serial magnetic resonance imaging (MRI) studies were the main tool for following patients' response and activity of the fungal lesions in conjunction with clinical and laboratory parameters. Treatment with amphotericin B was continued until resolution of all clinical symptoms and signs attributable to HSC, obtaining negative blood cultures and the appearance of at least healed lesions on MRI. Amphotericin B was discontinued in four patients because of severe nephrotoxicity (two patients), or continuous fever and persistent fungal lesions on MRI (two patients). Amphotericin B lipid complex (ABELCET) was successfully used as salvage therapy for these refractory patients. Four patients died with evidence of HSC despite treatment and supportive measures. The response rate for treatment of HSC was 82%. The mean total dose of amphotericin B including empirical treatment was 4 g and the median duration of treatment for responding patients was 112 d. The median number of days of anti- fungal treatment before the disappearance of fever was 19 d. Our results confirmed the need for protracted courses of antifungal agents for the successful eradication of HSC. Chemotherapy for the underlying disorder should not be interrupted or delayed in order to treat HSC.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever, hepatosplenomegaly, hemolytic anemia, and polyclonal hypergammaglobulinemia. Morphologically, the involved lymph nodes demonstrate complete effacement of the normal architecture, prominent neovascularization and infiltration by immunoblasts and plasma cells. Other terms that have been used to describe this entity include diffuse plasmacytic sarcomatosis, immunoblastic lymphadenopathy, lymphogranulomatosis X, and immunologic aberrations in idiopathic reticulosis. Initially, AILD was thought to be a disease of B-cell origin that represented reactive immune response to unknown stimulus and high potential for malignant transformation. It is now evident that AILD in 80% of cases follows an aggressive course with short median survival, especially, if complete response with chemotherapy is not achieved. Immunologic and molecular studies have demonstrated that the majority of AILD cases are T-cell clonal disorders. Despite the numerous reports on the role of Epstein-Barr virus in this disorder, it is unknown whether the presence of this virus is associated with the immune defect that accompanies AILD, or whether it is a pathogenetic factor. In contrast to non-Hodgkin’s lymphomas, a stage is not usually assigned to the patient since the disease is systemic in nature, subsequently, parameters such as extent of disease and tumor bulk used to identify high-risk patients with non-Hodgkin’s lymphomas, do not appear to correlate with disease activity or prognosis in AILD. Treatment of AILD has been unsatisfactory, with approximately 25% of patients achieving complete and sustained remission when combined chemotherapy agents are used. This article is devoted to a discussion of the different manifestations, suggested pathogenesis, and treatment of AILD.

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.

We describe our 6-year experience in the prospective examination of patients with suspected hepatosplenic fungal disease to show the diagnostic accuracy of MR imaging and the spectrum of appearances on MR images.All patients who underwent MR examination for suspected hepatosplenic fungal disease from January 1990 to January 1997 in three university institutions were included in the study. Patients presented with persistent fever or no response to antibacterial antibiotics. Patients were grouped as acute, subacute treated, and chronic treated, according to the duration of their symptoms. Patients with 2 weeks or fewer of possible infection were acute presentation, patients on antifungal therapy longer than 2 weeks but shorter than 3 months were subacute treated presentation, and patients on antifungal therapy for 3 months or longer or who had completed antifungal therapy and had a history of hepatosplenic fungal disease were chronic treated presentation. MR studies were prospectively interpreted for the presence of hepatosplenic fungal lesions. The appearances of fungal lesions in patients in each category were determined. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detecting lesions in patients with acute presentation were also determined.Sixty-nine patients were included in the study. MR imaging revealed signs consistent with hepatosplenic fungal lesions in 22 (32%) of 69 patients and no demonstration of hepatosplenic lesions in 47 (68%) of 69 patients. In the 60 patients with acute presentation, MR imaging in 13 patients revealed hepatosplenic lesions that were interpreted as fungal disease. True-positive lesions were present in 11 of these 13 patients. These lesions measured less than 1 cm in diameter and were best shown as well-defined high-signal-intensity foci on T2-weighted images. The remaining two of the 13 patients had false-positive lesions; one was shown to have tuberculosis, and the other had graft-versus-host disease. For acute presentation, MR sensitivity was 100%, specificity was 96%, positive predictive value was 85%, negative predictive value was 100%, and accuracy was 97%. In the five patients with subacute presentation, lesions were present that measured less than 1 cm in diameter and were best shown as mildly hyperintense on T1-weighted images. A perilesional ring nearly void of signal intensity was seen on unenhanced and gadolinium-enhanced T1-weighted images in all five patients. The four patients with chronic healed lesions all had lesions that were 1-3 cm in diameter with irregular, angular polygonal margins. These lesions, which were best shown on images obtained immediately after gadolinium administration, appeared as regions of diminished enhancement with no perilesional changes.MR imaging has high diagnostic accuracy for the diagnosis of acute hepatosplenic fungal disease. Patients with acute, subacute treated, and chronic healed presentations may have lesions that can be distinguished by their MR appearances.

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.

We have treated 10 patients with relapsed or refractory T-cell malignancies using gemcitabine. The drug was administered intravenously over 30 min at a dose of 1200 mg/m2 on d 1, 8 and 15 of each 28-d cycle. The mean age of the patients was 62 years and the mean number of administered cycles was three. Of the 10 patients, two achieved a complete response and four a partial response, for an overall response rate of 60% (95% confidence interval 20--35%). The toxicity of chemotherapy was mild and manageable in all patients. These encouraging results warrant further investigation of gemcitabine either as a single agent or in combination regimens as early salvage treatment for patients with refractory T-cell haematological neoplasms.

Inhibitors against Factor VIII Associated with the Use of Interferon-alpha and Fludarabine

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.

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.

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.

Nodular liver infiltration with multiple myeloma is very rare and its findings on MR images have not been, to our knowledge, previously described. The authors report a case of light chain multiple myeloma nodular liver involvement and describe its appearance on US and MRI. Despite their rarity these lesions have distinct MRI features and should be considered in the differential diagnosis of multiple lesions with high SI on T1-weighted images.

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.

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: Chronic disseminated candidiasis (CDC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy. Recent studies have provided evidence for diagnostic alternatives to invasive procedures and more therapeutic options for the management of this complication. In order to put diagnostic criteria and methodological approach to the disease into the perspective of developing strategies for therapy, all relevant studies published in the English literature over the last 30 years were examined. Materials and methods: The English-language articles located through MEDLINE (1966 to present) and from selected bibliographies. Results: There is increased recognition of CDC as complication of treatment with chemotherapy in patients with acute leukemia. Liver biopsy may not always be revealing or feasible to perform in some patients. Among the imaging modalities, magnetic resonance imaging has obtained preeminence as a non-invasive tool for the diagnosis of hepatosplenic fungal infections. Administration of amphotericin B (Amp B) in relatively large cumulative doses is needed to ensure appropriate control of the infection and prevention of future relapse. Patients intolerant of, or refractory to conventional Amp B have been successfully salvaged using fluconazole or lipid formulations of Amp B. A constellation of clinical, laboratory and radiologic parameters should be used to determine response and efficacy of therapy. There is sufficient evidence to support the safety and feasibility of continuing chemotherapy for acute leukemia in conjunction with antifungal treatment in patients diagnosed with CDC. Conclusion: The development of CDC in patients with acute leukemia does not preclude further chemotherapy or constitute contraindication for bone marrow transplantation. Knowledge of the course and pattern of evolution of the disease and adopting aggressive therapeutic approach will likely reduce the morbidity and mortality from this complication.

In this study, we assessed the ability of erythropoietin (EPO) to synergize with various chemotherapeutic agents and suppress the growth and metastasis of solid tumors. Animals were inoculated with Lewis lung carcinoma (LLC) cells and treated with EPO alone, the designated chemotherapeutic drug (cisplatin, mitomycin C or cyclophoshamide) alone, or EPO and the drug. Tumor volume was monitored daily. Thirteen days following cell injection, tumor mass was determined. In addition, the number of the metastatic foci in the lungs was determined. Cisplatin alone was capable of inducing a 7-fold decrease in final tumor volume compared to tumor-bearing animals injected with saline. However, when EPO was combined with cisplatin, the animals experienced an 11-fold reduction in final tumor volume compared to saline-injected animals (P

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.

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.

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.

Tumor-associated proteases play a major role in determining the biologic behavior and aggressiveness of prostate cancer. Several authors have described the association between the increased levels of urokinase plasminogen activator in the plasma and in the malignant prostatic tissue with the metastatic potential of prostate cancer. However, the direct effect of this activity in producing fibronogenolysis in patients with prostate cancer has not been addressed. To evaluate the role of chemotherapy in reversing fibrinogenolysis in patients with prostate cancer, eight patients with hormone-refractory prostate cancer, bleeding, and laboratory evidence of primary hyperfibrinogenolysis were treated with docetaxel. The drug was given 48 hr after initiation of all supportive measures. Laboratory data, including plasminogen, alpha 2-antiplasmin, and fibrinogen, were recorded before and after treatment. Prostate-specific antigen (PSA) was measured at the time of referral and before subsequent cycles (3 weeks). Five patients had resolution of the fibrinolytic process after one cycle of treatment with docetaxel. This was demonstrated by improvement in both the laboratory parameters and the bleeding episodes. Further follow-up showed stabilization of the hematologic parameters and reduction in PSA values in these patients. Two patients died from uncontrolled bleeding despite all supportive measures. One patient did not demonstrate response to this treatment in terms of normalization of the fibrinolytic indicators or reduction in PSA. Primary fibrinogenolysis associated with metastatic prostate cancer is a serious complication. Docetaxel appears to be effective in reversing this process in some hormone-refractory patients. Although this response appears to be due to antitumor activity, a direct effect on the fibrinolytic pathway induced by the tumor cannot be excluded. Further work in this area is warranted.

To determine the efficacy of combined preoperative chemotherapy and radiation therapy for locally advanced rectal carcinoma and the rate of sphincter conservation, a retrospective survey of 39 patients with locally advanced rectal carcinoma treated with various 5-fluorouracil- and leukovorin-based chemotherapy regimens and radiation prior to surgery in a single institution was reviewed. Toxicity, local control and survival were evaluated and compared to previous studies with similarly staged patients. Long-term follow-up was available on 35 patients. The actuarial local failure was 5.7% while the actuarial 5-year survival was 87%. The mortality rate was low (2.5%) and the rate of long-term serious complications acceptable (11.4%). Combined preoperative chemotherapy and radiation provided excellent local regional control despite the poor prognostic factors associated with size, fixation, and the initial advanced tumor stage with acceptable morbidity. In addition, patients with tumors located in the lower third of the rectum may be able to undergo sphincter-sparing surgery. Although the median follow-up is relatively short (32.4 months), the results are in accordance with previous studies of neoadjuvant combined chemotherapy and radiation for locally advanced rectal carcinoma in terms of local and distant control.

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.

Liver disease is associated with a wide variety of abnormalities of the coagulation system and often with severe bleeding. Knowledge of the effects of liver disease and its complications on the various clotting factors may be useful in differential diagnosis. Therapy is difficult but should be approached in a stepwise fashion, with attention to the potential hazards of each intervention. The coagulation system and its interrelationship with liver function can be complex. To ensure the best care of patients with liver disease and bleeding, primary care physicians should not hesitate to enlist the assistance of specialists in clotting disorders and a reliable coagulation laboratory.

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 single, optimal screening laboratory test for hemostasis would evaluate vascular, platelet, coagulation, and fibrinolytic functions. Unfortunately, such a test does not exist. The key factor in determining the presence of a bleeding diathesis is obtaining a detailed patient history. Results of coagulation tests should always be interpreted in the context of such a history. Screening tests include platelet count, PTT, and PT. Subsequent investigations depend on the results of these tests.

Combined hereditary deficiency of coagulation factors V and VIII is a very rare bleeding disorder. The severity of bleeding is determined by the level of these factors, although in general, this is less striking than the severe deficiency of either factor alone. We describe in this article a patient with this congenital defect, and the preoperative management for major surgery.

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.