Da Piers

Sentinel Lymph Node Procedure Is Highly Accurate in Squamous Cell Carcinoma of the Vulva

PURPOSE To determine the diagnostic accuracy of the sentinel lymph node procedure in patients with squamous cell carcinoma of the vulva and to investigate whether step sectioning and immunohistochemistry of sentinel lymph nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS Between July 1996 and July 1999, 59 patients with primary vulvar cancer were entered onto a two-center prospective study. All patients underwent sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with technetium-99m-labeled nanocolloid and intraoperative blue dye). Radical excision of the primary tumor with uni- or bilateral inguinofemoral lymphadenectomy was performed subsequently. Sentinel lymph nodes and lymphadenectomy specimens were sent for histopathologic examination separately. Sentinel lymph nodes, negative at the time of routine pathologic examination, were re-examined with step sectioning and immunohistochemistry. RESULTS In 59 patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and 48 bilateral). All sentinel lymph nodes, as observed on preoperative lymphoscintigram, were identified successfully intraoperatively. Routine histopathologic examination showed lymph node metastases in 27 groins, all of which were detected by the sentinel lymph node procedure. The negative predictive value for a negative sentinel lymph node was 100% (97.5% confidence interval [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that were negative at the time of routine histopathologic examination. CONCLUSION Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.

99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein.

99mTc-sestamibi (99mTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, 99mTc-MIBI was evaluated in the GLC4 cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC4/ADR sublines as well as in the S1 cell line and its MRP-transfected subline S1-MRP. 99mTc-MIBI concentration decreased in the GLC4/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in S1. 99mTc-MIBI plus vincristine increased 99mTc-MIBI concentration in GLC4 lines compared with 99mTc-MIBI alone. 99mTc-MIBI efflux raised with increasing MRP expression in the GLC4 lines. Glutathione depletion elevated 99mTc-MIBI concentration in GLC4/ADR150x. Cross resistance for 99Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC4/ADR150x vs GLC4. 99Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC4/ADR150x. These results show that 99mTc-MIBI is involved in MRP-mediated efflux. The fact that 99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this gamma-rays-emitting complex is tested for tumour efflux measurements.

Malignant struma ovarii treated by ovariectomy, thyroidectomy, and 131I administration

A 36‐year‐old woman presented with an intraperitoneally disseminated malignant struma ovarii, diagnosed by histopathology and 131I scintigraphy. The serum thyroglobulin level was elevated, and immunoperoxidase staining for thyroglobulin was positive for disease both in the tumor cells lining the follicles and in the colloid. The patient was treated successfully by a bilateral ovariectomy followed by a total thyroidectomy and administration of radioactive iodine. The clinical behavior and the presence of thyroglobulin in both serum and tumor tissue demonstrate the similarity between neoplastic thyroid tissue in the ovary and in the thyroid gland.

CHOLECYSTOKININ IS A PHYSIOLOGICAL HORMONAL MEDIATOR OF FAT-INDUCED INHIBITION OF GASTRIC-EMPTYING IN MAN

Abstract. The effect of cholecystokinin‐33 on gastric emptying was studied in eight healthy men. The test meal was a firm custard pudding, labelled with 99mTc‐Chelex‐100 particles. Gastric emptying rate was measured, using a dual‐headed gamma camera, and was expressed as the half time of the emptying curve. Plasma cholecystokinin concentrations were determined by radioimmunoassay. Subjects were studied three times: (i) during infusion of saline; during cholecystokinin infusion, (ii) 0·375 IDU kg−1 h−1 and (iii) 0·75 IDU kg−1 h−1. Furthermore, plasma cholecystokinin was determined after a regular meal. During saline, plasma cholecystokinin increased minimally. After the regular meal it increased from 1·6 to 6·5 pmol l−1 at 30 min, decreasing to 5·3 pmol l−1 at 60 min. During the lower and higher doses of cholecystokinin it increased from 10 and 1·4 to 4·5 and 7·3 pmol l−1, respectively. The lower and higher doses significantly (P < 0·05) increased half emptying time, from 45 ± 8 to 86 ± 17 and 198 ± 50 min, respectively. Cholecystokinin is most likely a physiological hormonal mediator of fat‐induced inhibition of gastric emptying.

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET)

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate α-lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.

Surgical experience in children with differentiated thyroid carcinoma

AbstractBackground: The optimal surgical treatment in children with well-differentiated thyroid carcinoma remains an important point of discussion. In this study, we evaluated our surgical experience and reviewed the literature accordingly to identify the most adequate treatment. Methods: We retrospectively analyzed 21 children, all under the age of 18 years at the time of diagnosis, with differentiated thyroid carcinoma (17 papillary, 3 follicular, and 1 Hürthle cell carcinoma). Total thyroidectomy was performed, followed by radioiodine therapy, as a part of the initial treatment in all patients. The results were compared with data from the literature. Results: Eleven children (52%) who presented with cervical lymph node metastases were treated by a modified radical neck dissection. Pulmonary metastases were seen at diagnosis in three patients. Six patients developed temporary complications. During follow-up, with a median of 11 years (range, 2–26 years), two patients (10%) developed recurrences, and no patient died during this observation period. A literature search confirmed our experience of excellent results without an increase of complications in the more aggressively treated patients. Conclusions: In children with differentiated thyroid cancer, treatment should consist of total thyroidectomy, followed by a modified radical neck dissection (when indicated) and iodine-131 ablation treatment. This aggressive approach seems to be justified because of the high incidence of nodal involvement and the low complication and recurrence rate after surgery.

Vulvar melanoma - Is there a role for sentinel lymph node biopsy?

The objective of this study was to evaluate the authors recent, preliminary experience with the sentinel lymph node procedure in patients with vulvar melanoma and to compare this experience with treatment and follow‐up of patients with vulvar melanomas who were treated previously at their institution.

Soft-tissue uptake of 99mTc-diphosphonate in systemic AL amyloidosis

A case of systemic AL (amyloid light-chain-derived) amyloidosis is presented, in which a 99mTc-diphosphonate bone scan demonstrated the intense uptake of tracer in the liver, spleen, heart, thyroid, oropharyngeal region, intestinal tract and uterus. The presence of amyloid deposits in these organs was confirmed at autopsy. A review of the literature is given. In amyloidosis, the binding of radionuclide-labeled calcium-seeking agents, such as diphosphonate and pyrophosphate, may be explained by the high calcium content of amyloid. The presence of calcium in amyloid is due to the presence of the non-fibrillar protein, amyloid P-component (AP). In our patient, the amyloid deposits reacted on immunofluorescence with antibodies directed against AP.A case of systemic AL (amyloid light-chain-derived) amyloidosis is presented, in which a 99mTc-diphosphonate bone scan demonstrated the intense uptake of tracer in the liver, spleen, heart, thyroid, oropharyngeal region, intestinal tract and uterus. The presence of amyloid deposits in these organs was confirmed at autopsy. A review of the literature is given. In amyloidosis, the binding of radionuclide-labeled calcium-seeking agents, such as diphosphonate and pyrophosphate, may be explained by the high calcium content of amyloid. The presence of calcium in amyloid is due to the presence of the non-fibrillar protein, amyloid P-component (AP). In our patient, the amyloid deposits reacted on immunofluorescence with antibodies directed against AP.

Low renal uptake of 99mTc-DMSA in patients with proximal tubular dysfunction.

In nine patients with different types of proximal tubulopathy and a nearly normal glomerular filtration rate a low uptake of 99mTc-DMSA in the kidneys was found. The underlying mechanism seems to be an increased urinary excretion of 99mTc-DMSA. This radiopharmaceutical might be used as a marker of proximal tubular dysfunction.

Reversible diminished renal 99mTc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis

AbstractA patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. 99mTc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of 131I-hippurate was preserved. Uptake of 99mTc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained.Thus, caution must be taken when interpreting results of 99mTc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of 99mTc-DMSA.