Pathways of lymphatic drainage from the breast.

BACKGROUND: The current standard for obtaining accurate sentinel lymph node (SLN) mapping is intraparenchymal lymphophilic dye/radiocolloid injection close to the breast tumor. We hypothesized that common lymphatic trunks drain both a large volume of breast parenchyma and skin and that intradermal or intraparenchymal routes flow to the same axillary node. METHODS: 99mTc-labeled filtered sulfur colloid was injected intradermally directly over the breast tumor in 119 patients. Blue dye was injected intraparenchymally in the same quadrant as the primary tumor (concordant quadrant) in 66 and in a discordant quadrant in 53 patients. During axillary exploration, both blue and gamma-emitting (hot) nodes were found. End points were SLNs that were hot and blue, either the same node or different nodes. RESULTS: In 62 (93.9%) of 66 of concordant quadrant and in 49 (92.5%) of 53 of discordant quadrant patients, the same SLN was both hot and blue (P = .99; Fisher's exact test). In eight cases in which two distinct nodes were blue and not hot and hot but not blue, the lymph nodes were very close to each other. CONCLUSIONS: The dermal and parenchymal lymphatics of the breast seemed to drain to the same axillary lymph nodes. Lymph from the entire breast seemed to drain through a small number of lymphatic trunks to one or two lymph nodes.

Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma.

Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received (111)In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of (111)In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T(1/2), blood AUC, plasma T(1/2), and plasma AUC. It is concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T(1/2), reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.

Developing an effective program to complete ictal SPECT in the epilepsy monitoring unit.

With the availability of more stable radiopharmaceuticals, the ictal single photon emission computed tomography (SPECT) perfusion study has emerged as a useful noninvasive functional neuroimaging tool in the presurgical evaluation of patients with medically intractable partial epilepsy. The purpose of this study was to determine whether the development of a program using trained electroencephalography (EEG) technologists to perform ictal injections in the epilepsy monitoring unit enabled a more efficient delivery of radiopharmaceuticals and therefore a higher specificity and sensitivity of outcome. All patients admitted to the epilepsy monitoring unit for prolonged video/EEG monitoring as part of the presurgical evaluation were eligible for completion of an ictal SPECT study using a three-way needle-free apparatus. Over a 19-month period, 85 (77%)) of 110 eligible patients were successfully injected during typical partial seizures. Various factors were analyzed including latency of ictal injection (27.3+/-20.8 [S.D.] s), radiopharmaceutical wastage (40% dose utilization), radiation safety parameters (1.6% contamination rate), and preliminary data of localizing value. Our results show that ictal SPECT can be a safe, noninvasive procedure completed on a routine basis in the epilepsy monitoring unit when appropriately trained support staff are utilized as part of a structured multidisciplinary program.

Sentinel lymph node uptake of two different technetium-labeled radiocolloids,.

BACKGROUND: The study was designed to compare the uptake of technetium-99m-labeled human serum albumin ([99mTc]HSA) and 99mtechnetium-labeled sulfur colloid ([99mTc]SC) in the sentinel lymph nodes (SLNs). METHODS: Radiocolloid levels in the SLN, femoral lymph node (FLN), ischial lymph node (ILN), spleen (SP), and right rear footpad (RRF) were quantitated over a period of 240 min after injection of [99mTc]SC or [99mTc]HSA into the rear footpad of C57 BL/6 mice. RESULTS: There was a significantly greater (p < 0.001) radioactive count in SLNs after [99mTc]SC (mean cpm 211,084.8) compared to [99mTc]HSA (mean cpm 115,640.8). In contrast, the counts in the FLNs were higher after [99mTc]HSA (mean cpm 11,333.4) than after [99mTc]SC injection (mean cpm 5,065.5). The percent uptake in the SP was higher after [99mTc]HSA than after [99mTc]SC injection. CONCLUSIONS: [99mTc]SC is rapidly and efficiently taken up by lymphatics at the primary injection site, is significantly retained in the SLN, and flows slowly to the next echelon node (FLN or ILN) and to the systemic circulation (SP). [99mTc]HSA tends to accumulate less efficiently in the SLN and to disperse more rapidly to the next echelon nodes and to the systemic circulation. By extrapolation, [99mTc]SC is likely to be a better radiocolloid for the intraoperative detection of SLNs.

Rates of flow of technetium 99m--labeled human serum albumin from peripheral injection sites to sentinel lymph nodes.

BACKGROUND: The new technique of sentinel lymphadenectomy for cutaneous melanoma provided us with a unique opportunity to quantitate the rates of lymphatic flow in afferent lymphatics. METHODS: Seventeen melanoma patients underwent preoperative lymphoscintigraphy with technetium 99m-human serum albumin (HSA). The time and distance between the injection site and the sentinel lymph node (LN) were recorded. By comparison, lymphatic flow rates between footpad, popliteal LN, femoral LN, and systemic blood were measured in 60 female mice (C57BL/6) after footpad injection of 99mTc-HSA. RESULTS: The rate of lymphatic flow to 14 axillary, four inguinal, one popliteal, and one parotid sentinel LNs averaged 10.4 +/- 7.3 cm/min. In contrast, the lymphatic flow rate between the footpad and the popliteal LN in mice (analogous to the sentinel LN in human beings) averaged 1.33 +/- 0.52 cm/min. There was a marked delay in the passage of radionuclide through the popliteal LN with consequent slowing of the rate of flow between the popliteal and femoral LNs to 0.22 cm/min. CONCLUSION: Lymphatic flow to the sentinel LN occurs rapidly from both human skin and murine footpads. This information might be helpful in planning the timing of the incision after vital blue dye injection for identifying the sentinel LN.

Scintigraphic demonstration of a right-to-left intracardiac shunt in a patient with massive pulmonary emboli.

A case of massive pulmonary embolism resulting in marked pulmonary to systemic shunting in a patient with a previously clinically inapparent ventricular or atrial septal defect is presented. The various types of unrecognized intracardiac shunts and their prevalence in the adult population are discussed.

Metoclopramide response in patients with progressive systemic sclerosis. Effect on esophageal and gastric motility abnormalities.

Twelve patients with progressive systemic sclerosis (four with CREST [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia] variant) underwent systematic evaluation to assess the esophagogastric effects of metoclopramide hydrochloride in this patient population. Esophageal manometry, esophageal radionuclide scintigraphy, solid-phase gastric emptying, and 24-hour esophageal pH monitoring were performed in all patients with and without metoclopramide. Metoclopramide improved lower esophageal sphincter pressure and reduced the gastric emptying delay and gastroesophageal reflux in most patients but had a less consistent effect improving esophageal transit or esophageal body pressures. Metoclopramide should be strongly considered in the pharmacologic approach to the gastroesophageal reflux-related complications of this disease.

Scintigraphic evaluation of duodenogastric reflux. Problems, pitfalls, and technical review.

Bile reflux has been implicated in the pathogenesis of gastritis, gastric ulcer, and esophagitis. Radionuclide techniques provide the only non-invasive method to detect duodenogastric reflux. To analyze the problems that occur with attempts at quantitation, 55 patients were prospectively evaluated (45 patients with reflux esophagitis or Barrett's esophagus and ten patients with clinical symptoms of bile reflux, four of whom had Bilroth II surgery) with Tc-99m DISIDA, using a fasting technique with gallbladder stimulation by sincalide. Visual duodenogastric reflux occurred in 16 of 55 patients. Overlap of small bowel with the stomach is the major problem for accurate quantitation and occurred in 20 of 55 patients (36%). Overlap of left lobe of the liver occurred in 40 of 55 patients (73%), but its contribution to gastric activity was slight and could be easily subtracted. Reflux was intermittent in six of the 16 positive studies (38%), and continuous computer acquisition is needed to detect its maximum value. Primarily because of the problem of small bowel overlap, scintigraphic evaluation of duodenogastric reflux is only, at best, semi-quantitative. A review of the technical variables used in this examination, as well as potential problems that can occur, is provided.

Scintigraphic detection of metoclopramide esophageal stimulation in progressive systemic sclerosis.

Supine radionuclide esophageal scintigraphy (RES) and manometry were used to prospectively evaluate metoclopramide effect on esophageal function and pressure amplitudes in 14 patients (12 females and two males; median time since diagnosis: 2 yr) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of percent emptying at 30 sec, and standard manometric measurements were obtained. RES and manometry were performed before and 10 min following the i.v. administration of metoclopramide. RES showed a significant increase in mean percent emptying from 36% to 46% after drug administration (p less than 0.01), while mean lower esophageal pressure (end-expiratory) increased from 2 to 11 mm of Hg (p less than 0.001). Manometry failed to reveal a significant increase in either distal or proximal mean esophageal contractile amplitude, and no correlation was found between the increase in percent emptying at RES and the change in lower esophageal pressure in the individual patient. RES is the only quantitative method presently available to evaluate bolus propagation in the esophagus, and it documented improved esophageal function after metoclopramide administration in a PSS population. When drug therapy is directed at augmentation of esophageal emptying, RES is an ideal method to evaluate drug response.

Barrett esophagus: decreased esophageal clearance shown by radionuclide esophageal scintigraphy.

Radionuclide esophageal scintigraphy is a sensitive test of esophageal function, but its usefulness is not well documented in Barrett esophagus. This technique was prospectively studied in 27 patients with histologically proved Barrett esophagus and 17 patients with biopsy-confirmed reflux esophagitis. The esophageal transit time and percentage of emptying were calculated. The only quantitative parameter of radionuclide esophageal scintigraphy to show a significant difference between the two conditions was the percentage of emptying, which was abnormal in 48% of patients with Barrett esophagus versus 31% of patients with reflux esophagitis. In the latter group, the mean percentage of emptying approached normal (89.5%), while in the former group it was decreased to 82.1% (P less than .05). Neither emptying parameter correlated with length of Barrett esophagus. These data support the hypothesis of inherent esophageal dysmotility in Barrett esophagus. Half of the patients with this condition have impaired esophageal clearance and may benefit from drug therapy.

Solid-phase gastric emptying in patients with Barrett's esophagus.

Delayed gastric emptying as a pathophysiologic factor in patients with gastroesophageal reflux (GER) is controversial. In order to further evaluate this question, we studied a population with severe reflux, specifically, patients with Barrett's esophagus. Solid-phase gastric emptying was measured in 17 patients and in 17 healthy volunteers using radionuclide imaging. Gastric emptying was variable among these patients with 70% normal, 18% rapid, and only 12% slow studies. From these observations, we conclude that delayed gastric emptying is unlikely to be a major factor in the pathogenesis of Barrett's esophagus.

Progressive systemic sclerosis: radionuclide esophageal scintigraphy and manometry.

Radionuclide esophageal scintigraphy (RES) and manometry were used for prospective evaluation of esophageal involvement and disease severity in 11 patients (nine women and two men; median time since diagnosis, 1 year) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of the percentage of emptying at 30 seconds, while manometry provided measurements of proximal, distal, and lower esophageal sphincter (LES) pressures. The findings of both RES and manometry were abnormal in all 11 patients. There was a high correlation between the percentage of emptying and either distal esophageal pressure (r = .86, P less than .01) or LES pressure (r = .79, P less than .01). No significant correlation was found between the percentage of emptying and proximal esophageal pressure (r = .28, P = .39). RES is a safe, simple procedure that is readily accepted by patients and can be used in place of manometry for the detection and staging of esophageal involvement in PSS.

The "3-D effect" of diffuse skin involvement by mycosis fungoides on gallium imaging.

A case of mycosis fungoides with diffuse cutaneous uptake of Ga-67 citrate is presented, and the possible causes of this uptake are discussed.