Stephen B. Strum

Observation of cells resembling Sternberg-Reed cells in conditions other than Hodgkin's disease.

The diagnosis of Hodgkins disease is based upon the finding of characteristic Sternberg‐Reed cells in appropriate cellular and architectural environments. The demonstration of cells with the nuclear and cytoplasmic features of Sternberg‐Reed cells is necessary, but not sufficient for the diagnosis of this disease. Many investigators, however, have erroneously regarded these cells as pathognomonic. This report emphasizes that cells indistinguishable from, or closely resembling, Sternberg‐Reed cells may be found in conditions other than Hodgkins disease. Their presence, therefore, should not be considered a diagnostic mandate. Thirteen cases are presented in which biopsy sections of both benign and malignant lesions revealed cells closely resembling or indistinguishable from Sternberg‐Reed cells.

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.

The persistence of Hodgkin's disease in long-term survivors

Abstract In a study of 280 patients with Hodgkins disease diagnosed at the University of Chicago between the years 1931 and 1964, forty patients (14.2 per cent) represented survivals of ten years or more. Of the forty patients, twenty-nine have died. Eighteen of these patients had postmortem examinations. In sixteen, histologic evidence of Hodgkins disease was observed. In the group of twenty-nine patients, the cause of death could be determined in twenty-one. Hodgkins disease could be implicated as a significant contributory cause of death in fourteen. In seven patients the cause of death could not be directly attributed to Hodgkins disease but to causes such as disseminated breast carcinoma, malignant melanoma, coronary occlusion, enteritis, nephritis and hepatitis secondary to radiation, pneumonia secondary to chemotherapy, pulmonary fibrosis secondary to radiation, and systemic coccidioidomycosis. In six of these, autopsies were performed and in four Hodgkins disease was present. In the patients with systemic coccidioidomycosis and pulmonary fibrosis no histologic evidence of Hodgkins disease was found. In the entire group of forty patients, the initial lymph node biopsy sections were available in thirty-seven and could be classified in thirty-five. Twenty-eight of these (80 per cent) showed nodular sclerosing Hodgkins disease, five showed Hodgkins disease with lymphocytic predominance and two showed Hodgkins disease with mixed cellularity. The finding of persistent Hodgkins disease in long-term survivors, especially in those dying from apparently unrelated causes, suggests that in some patients with Hodgkins disease clinical cure may in fact represent a state of equilibrium in which the host has come to terms with his disease.

Vascular invasion in Hodgkin's disease: Its incidence and relationship to the spread of the disease

Blood vessel invasion in Hodgkins disease has rarely been reported in lymph node biopsies. Although this phenomenon may occasionally be noted in hematoxylin and eosin‐stained sections, it is more readily demonstrable when elastica stains are employed. In all biopsy sections, the involved vessels were veins. Blood vessel invasion was most frequent in Hodgkins disease with lymphocytic depletion, according to the Rye modification of the classification of Lukes and Butler; it occurred in approximately 50% of these cases. This high incidence in the reticular type of Hodgkins disease was accordingly associated with the presence of extensive disease (80% of the patients with vascular invasion were stage III or IV) and with a relatively short survival. The phenomenon of blood vessel invasion in Hodgkins disease tends to support the concept of Hodgkins disease as a malignant neoplasm. It is essential to explain bone marrow and visceral involvements other than those occurring by contiguity.

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. Cancer 53:1432‐1439, 1984.

Significance of focal involvement of lymph nodes for the diagnosis and staging of Hodgkin's disease

Six cases of Hodgkins disease in which lymph node biopsy sections demonstrated only minute foci of Hodgkins disease are presented. The lymph node sections showed an essentially preserved nodal architecture and a cellular composition that in most areas was not suggestive of Hodgkins disease. It is our intention to emphasize the need for careful examination of lymph node sections in which clues suggesting early involvement of a lymph node by Hodgkins disease can be found. This is of great importance in both diagnosis and staging of the disease. The focal obliteration of subcapsular sinuses, the finding of foci of inflammatory cells, the discovery of atypical, malignant‐appearing histiocytes, and an increase in the deposition of collagen, occasionally in a band‐like fashion, should alert the pathologist to search for conclusive evidence of focal involvement of a lymph node by Hodgkins disease.

Further observations on the biologic significance of vascular invasion in Hodgkin's disease

Vascular invasion was detected in the pretreatment lymph node biopsy sections in 9, or 5.9%, of 153 patients with Stage I or II Hodgkins disease. This finding was associated with a greater than twofold increase in extension of disease to nonadjacent areas and with a life‐table survival at 18 months almost one‐half that of cases without evidence of vascular invasion. Of the 9 cases of vascular invasion, 4 occurred in Hodgkins disease of the nodular sclerosing type and 4 in Hodgkins disease with mixed cellularity. The finding of vascular invasion in lymph node biopsy sections from patients with Hodgkins disease regardless of histologic type appears to be a feature indicating an increased risk of the occurrence of nonadjacent or extranodal disease, or both.

Vascular invasion in Hodgkin's disease: Its relationship to involvement of the spleen and other extranodal sites

In 6 of 29 (20.7%) patients surgically staged for Hodgkins disease, vascular invasion was demonstrated in either sections of the diagnostic lymph node biopsy or spleen removed at the time of laparotomy. Surgical staging showed that patients with this histologic feature had either Stage III or IV disease; only 43.5% of those in whom vascular invasion was not seen had such extensive disease. In addition, involvement of either the liver, lung, or bone marrow was found in 5 of 6 patients with vascular invasion while only one patient without this feature showed visceral involvement. These findings suggest that vascular invasion is a histopathologic feature of important prognostic value, since it may indicate that hematogenous dissemination has occurred. The association of vascular invasion of the spleen with unequivocal liver involvement in 2 of 3 cases suggests that hematogenous dissemination of Hodgkins disease via the portal system may be a pathway for the spread of the disease to the liver.

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.

Inviting Patients to Read Doctors' Notes

BACKGROUND Fibric acid derivatives (fibrates) have been shown to increase serum creatinine level in randomized trials. OBJECTIVE To assess renal outcomes in elderly adults within 90 days of a new fibrate prescription. DESIGN Population-based cohort study. SETTING Ontario, Canada. PATIENTS Patients aged 66 years or older with a new outpatient prescription for a fibrate or ezetimibe (comparator drug) between January 2004 and December 2008. MEASUREMENTS Hospitalization for an increase in serum creatinine level (primary outcome) and consultation with a nephrologist, receipt of dialysis for severe acute kidney injury, all-cause mortality, and increases in serum creatinine level (secondary outcomes). All outcomes were assessed within 90 days of a new prescription for ezetimibe or a fibrate. RESULTS Compared with ezetimibe users (n = 61,831), fibrate users (n = 19,072) were more likely to be hospitalized for an increase in serum creatinine level (adjusted odds ratio, 2.4 [95% CI, 1.7 to 3.3]) and were more likely to consult a nephrologist (absolute risk difference, 0.15% [CI, 0.01% to 0.29%]; adjusted odds ratio, 1.3 [CI, 1.0 to 1.6]). There were no differences between groups in the risk for all-cause mortality or receiving dialysis for severe acute kidney injury. In a subpopulation of 1110 patients (fibrates, n = 220; ezetimibe, n = 890), 9.1% of fibrate users and 0.3% of ezetimibe users had an increase in serum creatinine level of 50% or more (absolute difference, 8.8% [CI, 4.5% to 13.1%]; odds ratio, 29.6 [CI, 8.7 to 100.5]). Risks were greater among fibrate users with chronic kidney disease. LIMITATIONS Because hospitalizations for an increase in serum creatinine level were underestimated, absolute differences may be misleading. Most patients (91%) were prescribed fenofibrate. Serum creatinine levels were measured as part of routine care and were not available for everyone or at predefined times. CONCLUSION New fibrate use in elderly adults was associated with an increase in serum creatinine level and a small 90-day absolute increase in hospitalizations and nephrologist consultations. There was no detectable effect on dialysis for severe acute kidney injury or on mortality. The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear. PRIMARY FUNDING SOURCE Ontario Ministry of Health and Long-Term Care Drug Innovation Fund.