Sacral neuromodulation for the treatment of faecal incontinence following proctectomy.

AIM: This study assessed the effectiveness of sacral neuromodulation (SNM) for faecal incontinence (FI) following proctectomy with colorectal or coloanal anastomosis. METHODS: An Institutional Review Board (IRB)-approved database identified patients treated for FI following proctectomy (SNM-P) for benign or malignant disease, who were matched 1:1 according to preoperative Cleveland Clinic Florida Faecal Incontinence Scores (CCF-FIS) with patients without proctectomy (SNM-NP). Primary outcome was change in CCF-FIS. RESULTS: Twelve patients (seven women) were in the SNM-P group and 12 (all women) were in the SNM-NP group. In the SNM-P group, six patients underwent proctectomy for low rectal cancer and five received neoadjuvant chemoradiation. Five patients had handsewn anastomosis, and one had stapled coloanal anastomosis. One lead explantation occurred after a failed 2-week SNM percutaneous trial. Six patients underwent proctectomy for benign conditions. Within-group analyses revealed significant improvement in CCF-FIS in the SNM-P group (reduction from a score of 18 to a score of 14; P = 0.02), which was more profound for benign disease (reduction from 14.5 to 8.5) than for rectal cancer (reduction from 19.5 to 15). SNM was explanted in 66% and 33% of patients after proctectomy for malignant and benign conditions, respectively. In the SNM-NP group, 41% underwent overlapping sphincteroplasty. One patient received chemoradiation for anal cancer. Within-group analysis for the SNM-NP group showed significant improvement in CCF-FIS (a reduction from 17.5 to 4.0; P = 0.003). There was significant improvement in CCF-FIS in patients without previous proctectomy (mean delta CCF-FIS: 11.1 vs 4.7; P = 0.011). Analysis of covariance (ANCOVA) reaffirmed that controls outperformed proctectomy patients (P = 0.006). CONCLUSION: SNM for FI after proctectomy appears less effective than SNM in patients without proctectomy, with high device explantation rates, particularly after neoadjuvant chemoradiation and proctectomy for low rectal cancer.

Regional lymph node status after neoadjuvant chemoradiation of rectal cancer producing a complete or near complete rectal wall response.

AIM: Transanal excision of the tumour site after complete response to chemoradiotherapy can determine the rectal wall response to treatment. This study was designed to assess whether the absence of tumour in the rectal wall corresponds to the absence of tumour in the mesorectum (true pathological complete response). METHOD: A retrospective review identified patients who underwent preoperative chemoradiation therapy for advanced mid and low rectal cancer followed by routine pre-planned radical surgery with total mesorectal excision. Patients in whom the pathology specimen showed no residual tumour in the rectal wall (ypT0) or a ypT1 lesion were assessed for tumour involvement in the mesorectum. RESULTS: Seventy-eight patients who underwent pelvic chemoradiation followed by radical surgery were reviewed. The rectal wall tumour disappeared in eight (ypT0). Of these, residual tumour was found in the mesorectum (ypT0N1) in one (12%) patient. Eleven patients were found to have ypT1 residual tumour. Of these, two (18%) had a final post-surgical staging of ypT1N1. CONCLUSION: Complete rectal wall tumour eradication was achieved in 10% of the patients, and downstaging to ypT1 was achieved in 14%. In 15% (12% in ypT0 and 18% in ypT1) of these patients, residual tumour cells were evident in the mesorectum. This would probably have rendered these patients with residual disease had a nonradical approach of transanal excision of the original tumour site been employed. Caution should be taken when considering the avoidance of radical surgery.

Peroxidase-catalyzed metabolism of etoposide (VP-16-213) and covalent binding of reactive intermediates to cellular macromolecules.

The horseradish peroxidase- and prostaglandin synthetase-catalyzed oxidative metabolism of the highly active anticancer drug, etoposide (VP-16-213), has been studied in vitro. This oxidation of VP-16 resulted in the formation of VP-16 quinone, an aromatic VP-16 derivative and the corresponding aromatic VP-16 quinone. This oxidative metabolism of VP-16 also resulted in the formation of reactive species that covalently bound to exogenously added DNA and heat-inactivated microsomal proteins. The peroxidase-catalyzed binding was time dependent and required the presence of cofactors (hydrogen peroxide or arachidonic acid). The prostaglandin synthetase/arachidonic acid-catalyzed metabolism and binding of VP-16 were inhibited by indomethacin, an inhibitor of the cyclooxygenase, and were shown to involve the peroxidative arm of prostaglandin synthetase. Our studies show that the protein covalent binding species were formed as a result of O-demethylation of the drug as shown by the loss of specifically labeled (O-14CH3) radioactivity from O-methoxy group and by incubating proteins with VP-16 quinones. In contrast, the covalent binding intermediates for DNA appeared to be different and VP-16-derived quinone methides are suggested as DNA binding species. Co-oxidation of VP-16 and the related drug, VM-26, during prostaglandin biosynthesis may be an important pathway for the metabolism of these agents and may play a role in their cytotoxic properties.

DNA strand breaks produced by etoposide (VP-16,213) in sensitive and resistant human breast tumor cells: implications for the mechanism of action.

Pleotropic resistant human breast cancer cells (MCF-7), selected for resistance to Adriamycin, were used to study the production of DNA strand breaks by etoposide (VP-16) and its relationship to drug cytotoxicity. It was shown that the resistant MCF-7 cell line was cross-resistant to VP-16, and the degree of resistance was found to be 125-200-fold. Alkaline elution studies indicated that the parental cell line was very sensitive to VP-16 which caused extensive DNA strand breakage. In contrast, little DNA strand breakage was detected in the resistant MCF-7 cells, even at very high drug concentrations, indicating a good agreement between strand breaks and cytotoxicity. Further studies indicated that the nuclei isolated from the parental cell line were more resistant to VP-16-induced DNA strand breaks than the intact cells, while the opposite was found in the resistant cell line. In addition, the alkaline elution studies in isolated nuclei showed only a 2-fold reduction of VP-16-induced DNA breaks in nuclei from the resistant cells. In agreement with this result, it was found that nuclear extract from the resistant cells produced 2-3-fold less VP-16-induced DNA breaks than that from the sensitive cells in 32P-end-labeled SV40 DNA. VP-16 uptake and efflux studies indicated that there was a 2-3-fold decrease in net cellular accumulation of VP-16 in the resistant cells. Although the reduced uptake of VP-16 and decreased drug sensitivity of topoisomerase II appear to contribute to the mechanism of action and the development of resistance to VP-16, they do not completely explain the degree of resistance to VP-16 in this multidrug-resistant MCF-7 cell line indicating that other biochemical factors, such as activation of VP-16, are also involved in drug resistance and suggesting that the resistance is multifactorial.

Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake.

PURPOSE: To assess the role of quantitative gallium citrate (Ga 67) single-photon emission computed tomography (SPECT) in differentiating lymphoma from benign hilar uptake, concentrations of Ga 67 in 29 sites of documented lymphoma and in 75 benign lesions were compared. PATIENTS AND METHODS: One hundred seven thoracic Ga 67 SPECT studies obtained in 101 consecutive lymphoma patients were reviewed. Fifty-nine studies detected Ga 67 uptake in the hilar and or mediastinal regions. Forty-eight studies showed no such abnormality. The concentration of Ga 67 in the thoracic lesions was measured using a quantitative SPECT technique and its nature was determined by correlation with computed tomographic (CT) scans and follow-up evaluation of the sites. RESULTS: In 20 of 59 abnormal studies (34%), there was lymphoma in the hilar and or mediastinal regions. In the remaining 39 abnormal studies (66%), Ga 67 uptake was benign. There were 29 sites of lymphoma and 75 benign lesions. The concentration of Ga 67 in lymphoma was significantly higher than in benign hilar uptake (13.2 +/- 5.4 %ID/mL x 10(-3) v 5.6 +/- 1.5 % injected dose (ID)/mL x 10(-3); P < .001). A concentration value of 8.3 %ID/mL x 10(-3) was found to best separate lymphoma and benign uptake, with a sensitivity of 90%, a specificity of 93%, a positive predictive value of 84%, and a negative predictive value of 96%. CONCLUSION: Lymphoma and benign hilar uptake differ significantly in their concentration of Ga 67. The present study shows that quantitative Ga-67 SPECT reliably differentiates lymphoma and benign uptake.

Utility of gallium-67 scintigraphy in low-grade non-Hodgkin's lymphoma.

PURPOSE: Low-grade non-Hodgkin's lymphoma (LGNHL) has traditionally been considered non-gallium-avid. The sensitivity of gallium 67 (67Ga) scintigraphy when using modern equipment and techniques in patients with LGNHL was investigated. MATERIALS AND METHODS: Fifty-seven consecutive patients with LGNHL underwent 67Ga scintigraphy at initial presentation (n = 40), when tumor progression occurred during treatment (n = 3), and at suspected disease recurrence after continuous clinical remission (CCR) (n = 14). Planar and tomographic images were obtained with either a very large field-of-view or a dual-head digital camera. Of 45 patients with Ga-avid LGNHL, 30 underwent 93 follow-up scans (one to six studies per patient). Scan findings were correlated with clinical and computed tomographic (CT) findings and with patient outcomes. RESULTS: 67Ga scintigraphy was positive in 45 of 57 patients (sensitivity, 79%) and in 113 of 164 disease sites (sensitivity, 69%). The sensitivity was higher in the more common types of LGNHL: follicular, predominantly small cleaved cell (FSC), and follicular, mixed small cleaved and large cell (FM) (84% and 91% in patients and 72% and 71% in disease sites, respectively). Sensitivity was lower in patients with mucosa-associated lymphoid tissue lymphoma (MALT) and small lymphocytic lymphoma (SL). Among 28 patients with disease recurrence after CCR (14 with and 14 without baseline studies), 67Ga scan was positive in 25, for a sensitivity of 89% for detection of disease recurrence. CONCLUSION: When modern technology is used, 67Ga scintigraphy has good sensitivity in patients with LGNHL. It therefore can be used to monitor response to therapy and to provide early detection of disease recurrence in these patients.

Adverse interaction between capecitabine and warfarin resulting in altered coagulation parameters and bleeding: case report and review of the literature.

Capecitabine can interact with warfarin, resulting in altered coagulation parameters and bleeding. Four cases have been reported. We describe a fifth case with life-threatening interaction between these two drugs. A 67-year-old female with metastatic breast cancer developed hemorrhagic blisters, purpura and ecchymoses. She had been well controlled on long-term warfarin (5 mg/day). Capecitabine was initiated 4.5 weeks prior to the bleeding episode. Laboratory work-up revealed an international normalized ratio of 8.56, partial prothrombin time of 61 seconds and prothrombin time of 5.2%. The coagulation parameters gradually normalized within 4 days following vitamin K administration and discontinuation of capecitabine and warfarin. Careful monitoring of coagulation parameters and proper adjustment of the warfarin dose are required in patients taking warfarin and capecitabine concomitantly.

[Cancer in Israel: mass mediated reality vs. real reality].

BACKGROUND: Cancer, being a terminal and often incurable disease, is a source of fear and concern for human beings. One of the most important sources of medical information in general, and cancer specifically, is the mass media. The media can shape beliefs regarding health and influence people's decision-making. The main hypothesis guiding this study, based on the theoretical framework of cultivation research, is that there will be considerable differences between media coverage and medical data regarding cancer in the Israeli population. METHOD: A systematic content analysis was applied to test this hypothesis, examining all the press reports (650 articles) published during the year 2000 in three of Israel's most popular daily newspapers--"Yedioth Ahronot", "Maariv" and "Haaretz". Data from the Israeli Ministry of Health was used for comparison with media reports to the population in terms of the types of cancer reported, the emphasis on death in the context of the disease, reports concerning treatment, and the age of cancer patients. RESULTS: The findings of the study are in accordance with the main hypothesis and show that the media's portrayal of cancer does not always reflect the medical reality regarding the above mentioned aspects. Several possible explanations are proposed in analyzing these findings, focusing mainly on the nature of news making and media selection, as well as on the impact of various interest groups such as pharmaceutical companies, hospitals. laboratories, oncology departments, and various organizations trying to promote awareness and raise funds for research. CONCLUSION: The findings of this study enhance a wide range of research in different areas of human knowledge that have documented processes of constructing "mass-mediated realities", but in the case of a fatal disease, the findings may have acute implications.

Primary lymphoma of the liver: clinical features and outcome of 9 patients.

PURPOSE: Primary liver lymphoma (PLL) is a rare lymphoproliferative disorder of unknown etiology. The prognosis in affected patients is poor, consisting of brief remissions, rapidly developing resistance to chemotherapy, early recurrence, and short survival. Most studies related to PLL are based on case reports. The aim of this retrospective study was to review our experience with PLL. PATIENTS AND METHODS: From 1985 to 2000, 9 patients who fulfilled the diagnostic criteria for PLL were treated at our hospital. All patients underwent a thorough work-up and were staged accordingly. RESULTS: The disease occured in middle and higher-aged patients (median age 63 years). Primary presenting complaints were abdominal pain, mainly in the right upper quadrant, and hepatomegaly. Liver function tests and lactate dehydrogenase (LDH) levels were elevated. Liver imaging (computed tomography-CT) and isotopic methods (gallium scan) demonstrated liver involvement either as solitary or multiple space-occupying lesions. Pathologic examination demonstrated diffuse, large cell (DLCL), B-type lymphoma in 7/9 (78%) patients. Doxorubicin-based chemotherapy was the mainstay of treatment. Good partial or complete remission rates were achieved in 7 patients, albeit for a brief period of time. CONCLUSION: Most patients with PLL succumb to their illness, despite its being relatively chemotherapy-sensitive. The introduction of intensive chemotherapy, plus/minus radiotherapy, and/or surgery has been considered in some studies.

Vinorelbine/VP-16 (etoposide) in metastatic breast cancer: a phase II study.

PURPOSE: This phase II study was conducted to evaluate the efficacy and tolerability of vinorelbine (navelbine) and oral VP-16 (etoposide) in pretreated metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Twenty-two female patients with therapy-resistant metastatic breast cancer were treated with vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and oral VP-16 50 mg/m(2)/day for 14 days. Cycles were repeated every 28 days. Treatment was given until clear evidence of disease progression. RESULTS: Complete remission was observed in 3 (14%) patients, and partial remission or stable disease in 10 (45%) patients. Median duration of response was 4 months (range 2-8). Symptomatic improvement, irrespective of imaging methods results, as evaluated through improved performance status (PS), the lack of requirement for urgent palliative radiotherapy, and a decrease in steroids and analgesics doses was demonstrated in 10 (45%) patients through a special questionnaire completed by all patients. Side effects were manageable. Dose modification due to leucopenic fever were necessary in only 3 patients. Previous radiation therapy did not mitigate the application of full doses of chemotherapy. CONCLUSION: Vinorelbine/VP-16 combination is active and tolerable in relapsed and heavily pretreated MBC patients.

Cancer and thrombosis revisited.

Remarkable progress has been made since the first description of the association between cancer and thrombosis by Trousseau over 100 years ago. Now, it is clear that there is a two-way connection between coagulation and cancer as tumor results in alterations in hemostatic balance, and thrombosis may promote tumor cell growth. A variety of clinical thrombotic syndromes may present in cancer patients including local and systemic venous and arterial thromboses. More evidence is now being gathered on the potential of antithrombotic regimens to prolong survival of cancer patients. Whether the use of novel antithrombotic drugs may result in a better outcome remains to be determined.

Cardiac valvular vegetations in cancer patients: a prospective echocardiographic study of 200 patients.

PURPOSE: Nonbacterial thrombotic endocarditis can complicate various malignancies and may cause morbidity and mortality mainly as a result of systemic embolism. The antemortem diagnosis of nonbacterial thrombotic endocarditis is rare. The purpose of our study was to assess the frequency, echocardiographic characteristics, and clinical correlation of nonbacterial thrombotic endocarditis in cancer patients. PATIENTS AND METHODS: A prospective echocardiographic screening of 200 nonselected ambulatory patients with solid tumors was performed. Patients were evaluated for evidence of thromboembolic events and for plasma D-dimer levels. A cohort of 100 consecutive patients without overt heart disease referred to echocardiography for the detection of an occult arterial embolic source served as a control group. It consisted of 52 males and 48 females, median age 60 years. RESULTS: The study group included 87 women and 113 men, median age 64 years (range 21 to 91). The frequent malignancies were lymphoma (26%), carcinoma of the gastrointestinal tract (20%), and carcinoma of the lung (16%). Cardiac valvular vegetations were found in 38 patients (19%) compared with only in 2 patients in the control group (2%, P < 0.001). Vegetations were found on the mitral or on the aortic valve in 19 and 18 patients, respectively. Isolated tricuspid valve vegetation was found in 1 patient. Valvular lesions were mostly common in patients with carcinoma of the pancreas (3 of 6, 50%), carcinoma of the lung (9 of 32, 28%), and lymphoma (10 of 52, 19%). Thromboembolism was diagnosed in 22 (11%) patients (12 deep vein thrombosis, 4 emboli to extremities, 2 cerebrovascular accidents, and 4 "silent" segmental left ventricular wall motion abnormalities on echocardiography). Thromboembolism was noticed in 9 of 38 patients (24%) with vegetations compared with 13 of 162 patients without vegetations (8%; P = 0.013). Plasma D-dimer level was examined in a subgroup of 170 patients. D-dimer level was increased in 19 of 21 patients (90%) with thromboembolism compared with 76 of 149 patients without thromboembolism (51%; P = 0.001). CONCLUSIONS: This study demonstrated a high prevalence of cardiac valvular lesions in patients with solid tumors. Vegetations were associated with thromboembolism. Plasma D-dimer level was significantly increased in patients with thromboembolism.

Acquired activated protein C resistance is common in cancer patients and is associated with venous thromboembolism.

PURPOSE: Cancer patients have an increased risk for venous thromboembolism. Because activated protein C resistance is a common risk factor for venous thromboembolism, we prospectively evaluated the activated protein C sensitivity ratio and factor V Leiden mutation in cancer patients with and without venous thromboembolism. SUBJECTS AND METHODS: We studied 55 consecutive cancer patients with deep vein thrombosis, 58 cancer patients with no history of venous thromboembolism, 54 patients with venous thromboembolism without malignancy, and 56 healthy controls. The presence of factor V Leiden mutation was determined by polymerase chain reaction and allele specific restriction digestion. The activated protein C sensitivity ratio was expressed as the ratio of activated partial thromboplastin times measured in the presence and absence of activated protein C; a ratio <2.0 in patients who did not have factor V Leiden was considered to indicate acquired activated protein C resistance. RESULTS: The prevalence of factor V Leiden mutation in cancer patients with thromboembolism (1 of 55, 2%) did not differ significantly from those in cancer patients without thromboembolism (4 of 58, 7%) or normal controls (2 of 56, 4%), but was significantly lower than that of patients with thromboembolism without cancer (18 of 54, 33%, P <0.001). The prevalence of acquired activated protein C resistance was significantly greater in cancer patients with thromboembolism (29 of 54, 54%, P = 0.001) compared with the other groups: 9 of 54 (17%) in cancer patients without thromboembolism, 7 of 36 (19%) in patients with thromboembolism without cancer, and none of the normal controls. CONCLUSION: Although factor V Leiden is not a major risk factor for thrombosis in cancer patients, acquired activated protein C resistance is common and may contribute to the thrombotic tendency in these patients.

Gallium-67 scintigraphy in lymphoma with bone involvement.

UNLABELLED: Both Hodgkin's and non-Hodgkin's lymphoma (NHL) may involve bone. Traditionally, 99mTc-MDP bone scintigraphy has been used to detect such involvement. In recent years, 67Ga scintigraphy has shown to be useful in monitoring treatment response in lymphoma. Although 99mTc-MDP has not been found particularly useful for monitoring bone response to cancer treatment, we were interested in whether 67Ga scintigraphy and SPECT could be used to monitor bone involvement with lymphoma. METHODS: Gallium-67 and 99mTc-MDP uptake were investigated in 20 patients with lymphoma involving the bone before treatment. Gallium-67 scans were done in 16 patients for monitoring response to treatment in the bone lesions. RESULTS: Gallium-67 studies diagnosed bone lesions in 19 of the 20 patients. Technetium-99m-MDP detected bone lesions in all patients investigated. In four patients, uptake by Ga-67 was more intense than 99mTc-MDP and in another four patients 99mTc-MDP uptake was more evident. Gallium-67, however, was useful in detecting other regions of involvement in 18 of the 19 patients with soft-tissue lymphoma lesions. Gallium-67 scintigraphy also correctly monitored bone response to treatment in all but one of the 16 patients who had 67Ga scintigraphy after completing therapy. CONCLUSION: Gallium-67 uptake by lymphoma involving the bone can be used to monitor osseous response to treatment.

Early detection of lymphoma recurrence with gallium-67 scintigraphy.

Early detection of tumor relapse in lymphoma patients is often a difficult diagnostic problem. CT, which detects a mass, often cannot differentiate between fibrosis or relapsed tumor. For this reason, we have studied the value of 67Ga scintigraphy in the diagnosis of tumor recurrence. The sensitivity of 67Ga scintigraphy in the detection of lymphoma recurrence was studied at an average interval of 8.7 mo following treatment in 32 patients who developed recurrent lymphoma. Its specificity was studied in 36 patients with no recurrence who were in continuous clinical remission. At the time of appearance of relapse, the sensitivity of whole-body 67Ga imaging was 95% and the specificity 89%. In 12 events of recurrence in 10 patients, 67Ga scintigraphy was abnormal at sites that later proved to be regions of relapse. In these patients, scintigraphy demonstrated recurrence an average of 6.8 mo before the appearance of clinical symptoms, findings on clinical examination or abnormality on CT or chest x-rays. Gallium-67 scintigraphy, which permits screening of the whole body for recurrence in a single study, was of particular value in evaluating lymphoma recurrence, since 27% of the recurrences were located exclusively in sites different from the original sites of disease. Gallium-67 scintigraphy appears to be a sensitive and specific test for restaging patients with lymphoma recurrence.

In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins.

We have studied the metabolism of VP-16-213 (etoposide, VP-16), an antitumor agent, by mouse liver microsomes to reactive intermediates and the subsequent covalent binding to microsomal proteins. This metabolism was shown to involve the O-demethylation of VP-16 and resulted in the formation of a 3',4'-dihydroxy derivative (DHVP-16) which was identified by both HPLC and mass spectrometry. The formation of DHVP-16 was cytochrome P-450-mediated as indicated by its dependence on NADPH, its increased production following treatment of mice with phenobarbital, and its marked inhibition by SKF-525A and piperonyl butoxide. Furthermore, DHVP-16 formation required oxygen. Microsomal incubation of VP-16 resulted in an irreversible binding of the drug to the proteins, which was also shown to be cytochrome P-450 dependent. The covalent binding of the VP-16 metabolite(s) was inhibited by DHVP-16 in a dose-dependent fashion, suggesting that the reactive intermediates that bound to proteins were derived from DHVP-16. Electron spin resonance studies indicated that the same semiquinone radical was formed during enzymatic (oxidation or reduction) metabolism of DHVP-16 and the o-quinone derivative of VP-16 (VP-16-Q). VP-16-Q and its semiquinone radical are suggested to be the bioalkylating species.

Spontaneous and stimulated nitroblue tetrazolium tests of leukocytes from patients with solid malignant tumors.

Histochemical nitroblue tetrazolium (NBT) reduction tests, spontaneous and endotoxin-stimulated, were performed on samples of blood from 202 adult patients with solid neoplastic tumors and 37 healthy control subjects. The patients were classified according to activity of the disease, chemotherapy, and presence of bacterial infection. The NBT test did not prove helpful in detecting the latter condition in these patients. Low median spontaneous reduction values were recorded for patients with active malignancies, or receiving chemotherapy, compared with controls or cured patients without chemotherapy. Stimulated reduction values were significantly lower for all groups of patients than for controls, although for those apparently cured and untreated, stimulated reduction attained significantly higher values than for the other patients. A leukocyte dysfunction caused by both the underlying disease and its chemotherapy is assumed, and the usefulness of the endotoxin-stimulated NBT reduction test in detecting this dysfunction is stressed.

Comparative study of the endotoxin-stimulated nitroblue tetrazolium test in disease and health.

Endotoxin-stimulated nitroblue tetrazolium (NBT) reduction was evaluated in 853 individuals: 270 healthy controls, 334 with various non-neoplastic conditions, 220 with solid non-lymphomatous tumours, and 29 with lymphoma. Each of the above groups was divided into three age subgroups: less than 60, 60-69, and greater than or equal to 70 years. In the controls and in patients with nonmalignant diseases, significantly lower values were recorded for elderly subjects (greater than or equal to 60 years) compared with younger subjects of the same group, whereas in cancer patients the results were independent of age. Under the age of 60, stimulated values for both patient groups were significantly lower than the control values, and in patients with solid non-lymphomatous tumours significantly lower values were attained than in the other patients. NBT reduction in lymphoma patients was comparable to that of the controls. In the elderly (age greater than or equal to 70) no significant differences were noted between patients and controls. It is suggested that stimulated NBT reduction declines with advancing age. While this test clearly demonstrates some leucocyte dysfunction in solid cancer, its value in investigating neutrophil behaviour in elderly subjects is questioned.