The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis.

AIM: To compare the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of lymph node metastases in prostate cancer. METHODS: After a comprehensive literature search, studies were included that allowed construction of contingency tables for detection of lymph node metastases using CT or MRI. In addition, a summary receiver-operating characteristic (ROC) analysis was performed. RESULTS: A total of 24 studies were included. For CT, pooled sensitivity was 0.42 (0.26-0.56 95% CI) and pooled specificity was 0.82 (0.8-0.83 95% CI). For MRI, the pooled sensitivity was 0.39 (0.22-0.56 95% CI) and pooled specificity was 0.82 (0.79-0.83 95% CI). The differences in performance of CT and MRI were not statistically significant. CONCLUSION: CT and MRI demonstrate an equally poor performance in the detection of lymph node metastases from prostate cancer. Reliance on either CT or MRI will misrepresent the patient's true status regarding nodal metastases, and thus misdirect the therapeutic strategies offered to the patient.

Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study.

This trial investigated the tolerability and effect of modified citrus pectin (Pecta-Sol) in 13 men with prostate cancer and biochemical prostate-specific antigen (PSA) failure after localized treatment, that is, radical prostatectomy, radiation, or cryosurgery. A total of 13 men were evaluated for tolerability and 10 for efficacy. Changes in the prostate-specific antigen doubling time (PSADT) of the 10 men were the primary end point in the study. We found that the PSADT increased (P-value<0.05) in seven (70%) of 10 men after taking MCP for 12 months compared to before taking MCP. This study suggests that MCP may lengthen the PSADT in men with recurrent prostate cancer.

Intermittent androgen deprivation in prostate cancer patients: factors predictive of prolonged time off therapy.

OBJECTIVES: We hypothesize that prostate cancer (PC) patients who achieve and maintain an undetectable prostate-specific antigen (UD-PSA) on androgen deprivation therapy (ADT) have a predominantly androgen-dependent cancer cell population sensitive to apoptosis that allows for a prolonged time off ADT. This study summarizes patient- and treatment-related factors associated with a prolonged time off ADT in patients electing intermittent androgen deprivation (IAD). METHODS: Hormone-naïve patients with PC were treated with ADT using an antiandrogen and a luteinizing-hormone-releasing hormone-agonist. Of 255 consecutive patients, 216 (85%) achieved a UD-PSA (< 0.05 ng/ml). Ninety-three (43%) of 216 elected to stop ADT after maintaining a UD-PSA for a median of one year. Patients were followed off therapy and advised to restart ADT if the PSA level reached > or = 5.0 ng/ml. Forty-one patients received finasteride as part of IAD induction and as maintenance off therapy; these patients are excluded from the current study and are the focus of another publication. The remaining 52 patients are assessable for response being either in the off-phase of IAD > or = 1 year or having restarted IAD. RESULTS: In the first IAD cycle, the median duration of the on-phase of IAD was 16 months (mean 19.0 months, range 3.6-71 months), and the median off-phase duration was 15.5 months (mean 24.1 months, range 3.2-87+ months). In 28 patients who maintained a UD-PSA for > or = 1 year, their median off-phase duration was 29 months (mean 35.8 months, range 7.8-87+ months), with nine (32%) still off IAD after a median follow-up of 62 months. Significant (p < 0.05) independent factors associated with prolonged off-phase duration by multivariate analysis included UD-PSA on ADT > or = 1 year (p = 0.010), PSA-only recurrence after local therapy (p = 0.039), and reaching a testosterone level > or = 150 ng/dl in > or = 4 months off ADT (p = 0.041). After a median of 66 months of follow-up, only one (2%) patient developed androgen-independent PC. CONCLUSIONS: Hormone-naïve patients who achieve and maintain a UD-PSA for at least one year during ADT may initiate IAD and anticipate a prolonged off-phase duration. Attainment of a UD-PSA on ADT may serve as an in vivo sensitivity test of a patient's tumor cell population, and allow for better selection of those best suited for IAD.

Anaemia associated with androgen deprivation in patients with prostate cancer receiving combined hormone blockade.

OBJECTIVE: To describe the incidence, time to onset and extent of anaemia occurring in patients with prostate cancer receiving combined hormone blockade (CHB) and the timing and extent of recovery from anaemia in those patients where CHB was discontinued. PATIENTS AND METHODS: Patients with prostate cancer were evaluated prospectively by physical examination and laboratory tests at baseline and at routine intervals while receiving CHB. Of 142 patients who received CHB, 133 were evaluable for the assessment of anaemia; CHB was discontinued in 76 patients, of whom 64 were assessable for recovery from their anaemia. RESULTS: Haemoglobin levels declined significantly in all patients from a mean baseline of 149 g/L to means of 139 g/L, 132 g/L and 131 g/L at 1, 2 and 3 months, respectively. Haemoglobin levels continued to decline during CHB to a mean nadir of 123 g/L at a mean of 5.6 months of CHB, representing a mean absolute haemoglobin decline at nadir of 25.4 g/L. In 120 of the 133 (90%) patients, the relative decline in haemoglobin at nadir was > or = 10% and was > or = 25% in 17 (13%) others, representing a mean absolute haemoglobin decline in this subset of 42.7 g/L. Significant symptoms related to anaemia occurred in 17 patients (13%). Anaemia and symptoms in these patients were easily corrected with the subcutaneous administration of recombinant human erythropoietin. CONCLUSIONS: The anaemia associated with androgen deprivation is significant and occurs routinely in men receiving CHB. It is normochromic, normocytic, temporally-related to the initiation of androgen blockade and usually resolves after CHB is discontinued. We suggest that patients receiving CHB undergo haematological testing at baseline, 1-2 months after initiating CHB and periodically thereafter. Patients developing anaemia should be questioned about symptoms reflecting physiological compromise (e.g. angina, dyspnoea on exertion). In the absence of other causes, CHB should be suspected in the development of anaemia in patients receiving this treatment.

Crk is required for apoptosis in Xenopus egg extracts.

Apoptosis is essential for the development and homeostasis of multicellular organisms. Recently, a cell-free extract prepared from Xenopus eggs was shown to recapitulate intracellular apoptotic pathways in vitro. While many stimuli have been shown to trigger apoptosis in a variety of cell types, the intracellular signaling pathways involved in apoptosis remain largely unknown. Here we show that addition of a recombinant protein containing the phosphotyrosine binding (SH2) domain from the adaptor protein crk, but not those derived from a panel of other signaling proteins, can prevent apoptosis in the Xenopus egg extract system. Furthermore, immunodepletion of endogenous crk protein from the egg extracts, or addition of anti-crk antisera to these extracts, prevents apoptosis. The ability to undergo apoptosis can be restored to these extracts by addition of recombinant crk protein. These results directly demonstrate that crk participates in apoptotic signaling.

Reaper-induced apoptosis in a vertebrate system.

The reaper protein of Drosophila melanogaster has been shown to be a central regulator of apoptosis in that organism. However, it has not been shown to function in any vertebrate nor have the cellular components required for its action been defined. In this report we show that reaper can induce rapid apoptosis in vitro using an apoptotic reconstitution system derived from Xenopus eggs. Moreover, we show that a subcellular fraction enriched in mitochondria is required for this process and that reaper, acting in conjunction with cytosolic factors, can trigger mitochondrial cytochrome c release. Bcl-2 antagonizes these effects, but high levels of reaper can overcome the Bcl-2 block. These results demonstrate that reaper can function in a vertebrate context, suggesting that reaper-responsive factors are conserved elements of the apoptotic program.

Nutrition, body condition, activity patterns, and parasitism of free-ranging troops of olive baboons (Papio anubis) in Kenya.

Three troops of olive baboons (Papio anubis) comprising 134 animals were captured during a translocation program. All three troops (PHG, CRIP, WBY) lived in high-altitude savannah, but two (CRIP and WBY) also frequented human settlements, where they had access to the garbage pits and vegetable gardens. The translocation offered the opportunity to compare body condition, activity patterns, and parasitism among the troops of animals. A variety of body measurements were taken, a physical examination performed, activity patterns for the previous 2 years enumerated, and blood and feces collected for virological and parasitological analyses. Body condition, as judged qualitatively by appearance and quantitatively by subcutaneous fat thickness and body weight, was lowest in PHG, the naturally foraging troop. All animals were negative for all viruses. No blood-borne parasites were found, but the feces of the majority of animals were positive for eggs of strongyles, ascarids, Trichuris spp., and Strongyloides spp. Quantification of strongyles indicated the heaviest burdens were in the non provisioned troop PHG. These results when combined with the behavioral observations that PHG spent more time foraging and less time resting or socializing than WBY suggest lowered availability and/or a poorer quality of PHG's diet. The data support the hypothesis of a causal relationship between host nutrition and helminth parasite infection but do not permit general conclusions to be drawn on mechanisms of interaction.

Improved methods for venous access: the Port-A-Cath, a totally implanted catheter system.

We prospectively evaluated the performance and rate of long-term complications with the Port-A-Cath (PAC), a totally implanted vascular access system. Two catheter styles were evaluated, a small-bore (SB) catheter (0.51-mm diameter) and a large-bore (LB) catheter (1.02-mm diameter), in conjunction with the use of a strict catheter care protocol. The PAC performed well, and with both SB and LB systems, no significant extravasation, skin necrosis, hematoma, septum damage or leakage, or subcutaneous portal infections occurred after 7,240 days of implantation and 1,435 days of use. Complications with the PAC system consisted of catheter occlusion (seven patients, 21.5%) and one instance of possible catheter infection (3.1%). Occlusions were limited to patients implanted with the SB catheter (seven of 16, 43.8%), and five of the seven (71.4%) occurred in patients receiving continuous infusion chemotherapy and/or total parenteral nutrition. Patency of the PAC system was maintained using a regular flushing schedule once every 30 days, a significant advantage compared with the daily maintenance schedule required with externally placed venous catheters. The results of this study suggest that the PAC system can provide a safe and reliable method for venous access in patients requiring intermittent or prolonged intravenous therapy.

Intrathoracic Hodgkin's disease. A case presentation with multiple pulmonary nodules in the absence of mediastinal or hilar node disease.

Patients with Hodgkin's disease (HD) most commonly present with peripheral lymph node enlargement. The finding of pulmonary parenchymal involvement is usually associated with hilar and/or mediastinal adenopathy; such instances are felt to represent spread to the lung by contiguity. Noncontiguous spread to peripheral lung parenchyma in the absence of hilar or mediastinal node involvement has rarely been reported. This is the first documented case report in a 32-year-old woman with nodular sclerosing HD. The unusual clinical presentation in this patient was associated with the histologic detection of vascular invasion in the lymph node and open-lung biopsy specimens.

Clinical pharmacokinetics of high-dose metoclopramide in cancer patients receiving cisplatin therapy.

Using a sensitive and specific high-pressure liquid chromatographic (HPLC) assay, we measured serum levels of metoclopramide in 18 cancer patients receiving high-dose intravenous (IV) therapy to prevent cisplatin-induced emesis. Ten patients were treated with one or more courses with metoclopramide alone (1.0 to 3.0 mg/kg) in an open-label study, and eight patients were treated with a fixed 2.0 mg/kg dose of metoclopramide with or without adjunct dexamethasone (20 mg) using a randomized, crossover design. The pharmacokinetics of metoclopramide were determined, and the relationship between serum levels and clinical response was evaluated. The pharmacokinetic parameters of high-dose metoclopramide were found to be similar to those reported for standard promotility doses, and no dose dependency was demonstrated over the range of doses studied. No clear correlation between serum metoclopramide levels and prevention of cisplatin-induced emesis was observed. The addition of dexamethasone resulted in clinical improvement in two of eight patients, but had no effect on serum metoclopramide levels or kinetic parameters. Results in this study population do not show metoclopramide levels to be related to antiemetic effect following IV cisplatin therapy.

High-dose intravenous metoclopramide versus combination high-dose metoclopramide and intravenous dexamethasone in preventing cisplatin-induced nausea and emesis: a single-blind crossover comparison of antiemetic efficacy.

We tested the safety and antiemetic effectiveness of intravenous (IV) dexamethasone (DXM) as an adjunct to high-dose IV metoclopramide (MCP) to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy. Response was determined by using objective and subjective criteria. Thirty patients were randomly assigned to receive MCP alone at a dose of 2 mg/kg IV for three doses or the same dose of MCP plus 20 mg of DXM IV for three doses. Twenty evaluable patients received a second course of cisplatin and were crossed over to the opposite arm. Study results did not show a statistically significant advantage of combination MCP plus DXM over MCP alone using strict objective criteria for antiemetic response. However, patients subjectively preferred MCP plus DXM over MCP alone by nearly a 6:1 ratio, regardless of the randomization sequence. Although the addition of DXM does not appear to objectively improve emetic protection with high-dose MCP, we recommend MCP plus DXM to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy when the use of steroids is not contraindicated, in view of patient preference for the combination.

Combination metoclopramide and dexamethasone: an effective antiemetic regimen in outpatients receiving non-cisplatin chemotherapy.

In a pilot study a combination of metoclopramide and dexamethasone was administered to 29 patients receiving emetogenic chemotherapy. Metoclopramide was given intravenously (IV) at a dose of 0.5 mg/kg one-half hour before the start of chemotherapy, and then given at the same dose orally two, five, and eight hours after chemotherapy. Dexamethasone was given at a dose of 10 mg IV immediately following the first dose of metoclopramide, then given at a dose of 8 mg orally six, 12, and 18 hours after chemotherapy. The chemotherapy regimens most commonly used were standard FAC, FAM, and BACOD regimens. Twenty-six of 29 patients received outpatient treatment. Complete protection against both nausea and vomiting was seen in 69% (20/29) patients; six others (21%) experienced mild nausea but no vomiting, resulting in 90% (26/29) of the patients having total emetic protection with combination metoclopramide and dexamethasone. Eighty-eight percent (15/17) of the patients with no prior chemotherapy had no nausea or vomiting, one (6%) had only mild nausea, and the remaining patient (6%) had one emesis. Forty-two percent (5/12) of the patients with prior chemotherapy had complete antinausea and emetic protection, five (42%) had nausea without vomiting, and the remaining two patients experienced one or two emesis. Side effects were minimal when present and included mild drowsiness (five patients), akathisia (three patients), diarrhea (one patient), and hot flashes (one patient). Combination metoclopramide and dexamethasone therapy can effectively prevent emesis in 94% of patients receiving potentially emetogenic chemotherapy and can prevent nausea and emesis in 88% of untreated patients. Studies defining the optimal dose and scheduling needed to maintain such antinausea and antiemetic protection are necessary.

Intravenous metoclopramide: prevention of chemotherapy-induced nausea and vomiting. A preliminary evaluation.

The authors tested the safety and efficacy of intravenous metoclopramide in the prevention of chemotherapy-induced nausea and vomiting. Those studied included hospitalized patients receiving their initial treatment with potent, emetogenic non-cisplatin-containing regimens, and outpatients receiving both their initial and maintenance non-cisplatin-containing chemotherapy. Fifty patients received metoclopramide with one or more of three intravenous metoclopramide dosage schedules, based on whether they received their chemotherapy on an inpatient or outpatient basis. Of the 50 patients treated, 39 (78%) achieved total protection (no emesis), and 9 (18%) attained major antiemetic protection (one or two emeses) when all dosage schedules of metoclopramide were combined. Therefore, total or major antiemetic protection was observed in 48 of 50 patients (96%) receiving a broad range of potentially emetogenic chemotherapy. Antiemetic protection was shown not to depend on the schedule of metoclopramide dosing used, but rather on the emetic potential of the chemotherapeutic agents or combinations employed. In addition, previously treated patients in whom chemotherapy-related nausea or vomiting had posed a significant problem in the past, were shown to have an overall lower incidence of total antiemetic and antinausea protection as compared with patients who were previously untreated or did not experience emesis with prior chemotherapy. Thirty patients experienced no nausea or vomiting with intravenous metoclopramide; in the 20 patients who experienced nausea, its incidence was shown to be directly proportional to the emetic potential of the chemotherapy agents employed. Side effects were dose-related, however none were serious enough to warrant drug withdrawal. It is concluded that intravenous metoclopramide possesses significant antiemetic activity in patients receiving potent, non-cisplatin-containing chemotherapy. The dosage and scheduling required to provide total protection against nausea and vomiting appears to be dependent on the inherent emetic potency of the chemotherapy used. Further studies involving large numbers of patients are required to determine the optimal dosage and scheduling of this agent.

High pressure liquid chromatographic analysis of metoclopramide in serum.

Metoclopramide has recently been approved at dose levels of 1 to 2 mg/kg for the treatment of nausea and vomiting resulting from cancer chemotherapeutic agents. A rapid, sensitive reverse phase HPLC quantitative procedure for metoclopramide in serum is described. The method involves a single-step extraction of metoclopramide and disopyramide (internal standard) from alkalinized serum into benzene and utilizes a reverse-phase C-8 system with a mobile phase of 11:22:66, methanol: acetonitrile: pH 3.7 acetate buffer, and UV detection at 268 nm. The method is highly reproducible and has a limit of sensitivity of 2.5 ng/ml from a 2.0 ml serum sample. The method has been successfully applied to clinical pharmacokinetic studies involving administration of IV oral metoclopramide to cancer patients receiving highly emetogenic cis-diamminedichloroplatinum.